The CTSI provides pilot funding for innovative translational research and the development of research methods at BU. That encompasses the continuum from the development of new therapies and diagnostic tests, to studies of the population health impact of health interventions.
The overarching goal of the BU CTSI Pilot Grant Program is to help investigators explore and solve major challenges in translational science, especially those that address the special health problems of our urban communities, by developing and deploying new tools, methods, and processes to expedite clinical and translational research and discovery.
We seek to stimulate individual and team science in all areas of translational research related to the prevention, diagnosis, and management of the human disease. Researchers who apply as a Team of 2-3 could build an application that has the potential to transition into a fundable ARC program in the future. Researchers engaged in translational basic/bench, clinical, biomedical, patient-oriented, implementation, and population health science research are encouraged to apply. The CTSI welcomes applications that are at all levels of the translational continuum including:
T1 research that develops novel treatments and interventions by expediting the movement between basic research and patient-oriented research leading to new or improved scientific understanding or standards of care.
T2 research that tests the efficacy and effectiveness of interventions through patient-oriented research and population-based research leading to better patient outcomes, the implementation of best practices, and improved health status in communities.
T3 research that promotes dissemination and implementation of research for system-wide change through the movement of evidence based-guidelines into clinical practice.
T4 research that promotes discoveries in population science.
COMING SOON: REQUEST FOR APPLICATIONS INTEGRATED PILOT GRANT PROGRAM ANNOUNCEMENT
Release Date: TBD
Application due date: TBD
Funding Announcement: January, 2023
Earliest Activation Date: April 1, 2023, or July 1, 2023 (for DOM funded awards)
Pilot Information Session
This RFA is open to ALL members of the BMC/BU community and represents a collaborative effort between the CTSI and partner organizations to fund meritorious research applicable to at least one (or more) of the components noted below: 1. CTSI General Funds 2. Community-Engaged Research 3. Bioinformatics/Mobile Health 4. BU School of Medicine (BUSM) 5. Henry M. Goldman School of Dental Medicine (GSDM) 6. Evans Center for Biomedical Research 7. Department of Medicine (DOM) 8. Addiction Science Research 9. New Product/Device Development CTSI seeks to encourage the development and evaluation of new products, devices, or drug targets that have commercial potential. While CTSI will support applicants at any stage of the development timeline, this mechanism is best suited to early feasibility studies and/or proof of concept. Specific studies could include, but are not limited to, in vitro development, model systems, animal studies, first-in-human testing, or new applications of existing technology. Applicants will be connected to institutional resources to support this process. Applicants must have a primary faculty appointment at Boston University, and the research to be conducted must be based at Boston University, Boston Medical Center, or any of their affiliated hospitals and health centers. Faculty with co-appointments at BU and BU/BMC affiliated institutions are also encouraged to apply. Please see above for additional eligibility requirements based on the component to which the applicant is applying. In particular, we encourage early investigators to apply. Including those with institutional or individual mentored research awards from NIH or Foundations. Recipients of previous CTSI awards are eligible to apply for awards to support new research projects, providing awards are at least two years apart. Individuals from under-represented groups are highly encouraged to apply. Applications from interdisciplinary teams of investigators are highly encouraged (see below for definition). Collaborations with investigators outside of the BU/BMC and affiliates are allowed, though justification should be provided. To search for BU collaborators, refer to BU Profiles or send a request to the BU CTSI Navigator team at email@example.com. Two award levels are offered: The level of funding awarded to successful applicants will be determined after a review of the budget request and budget justification. Funds may be used for any purpose to support the proposed research. Typical expenses include: Funds may not be allocated to PI or Co-I salary. Awards are not transferable to any other institution (sub-awards are not allowed). Pilot grants are not intended to supplement existing funded awards. Significant overlap in Pilot grant Aims with Aims from a funded grant must be disclosed and justified at the time of submission. Research Proposed in response to this RFA must be accomplished within the specified award period. IRB and IACUC Approvals: All IRB and IACUC protocols must be approved prior to the expenditure of any funds. Delayed Onset Human Subjects Research: The NIH requires that the CTSI obtain explicit approval from the NIH for any CTSI funded pilot with research involving human subjects. Accordingly, the IRB-approved protocol and other materials must be submitted to the NIH at least 45 days prior to the project start date. CTSI personnel will work with awardees to meet these requirements for those pilots that are funded with CTSI grant funds. Prior Approval of Vertebrate Animals Research: We strongly advise all Pilot grantees to begin the IRB/IACUC approval process at the time of final grant submission. If you are selected for funding, you will be required to provide your IRB/IACUC approval before funds are released to you. If at the time of notice of award, you have not submitted your IRB/IACUC application, you will be required to meet with a CTSI IRB/IACUC consultant within 2 weeks and expected to follow a strict timeline for regulatory submission. An award may be rescinded for failure to secure IRB/IACUC approval 3 months after notice of award. All applications can be submitted here and must include: Applications will be reviewed by the BU CTSI Scientific Review Committees comprised of faculty with relevant expertise analogous to the NIH review process (with a focus on Significance, Innovation, Approach, and Investigators). Specific review criteria include, but are not limited to:
Priority Areas of this RFA
Any CRC or BMC/BUMC faculty member may apply to this component. While all areas of investigation are eligible, the CTSI is particularly interested in supporting research that involves special populations served by BMC/BUMC including (but not limited to) children and adolescents; the elderly; underserved and low socioeconomic status (SES) patients; as well as and diseases that affect patients across their lifespan.
Any CRC or BMC/BUMC faculty member may apply to this component. These projects must be designed to stimulate community-academic partnerships with the goal of catalyzing innovative translational research that is responsive to community health needs. We define community as the diverse, under-resourced populations served by Boston Medical Center and its affiliated community health centers.
Any CRC or BMC/BUMC faculty member may apply to this component. These projects must leverage existing bioinformatics resources or mobile health applications to facilitate improved health outcomes, facilitate access to care, or address health disparities among vulnerable populations.
Faculty whose grants are submitted through BUSM (BU Office of Sponsored Programs) are eligible to apply for this funding element. For all projects submitted in this area, there is a preference for coordinated applications from multiple investigators. “Applications related to research in breast & prostate cancer, sexual medicine, neuroscience, and collaborations with Chinese universities (not Taiwan) are strongly encouraged. Applications for up to $50K will be considered.
This funding element specifically funds meritorious applications from GSDM faculty.
The CTSI will support new research programs that align with existing Affinity Research Collaboratives (ARCs) projects supported through the Evans Center for Interdisciplinary Biomedical Research (http://www.bumc.bu.edu/evanscenteribr). This element is intended to:
• Fund projects from non-ARC affiliated investigators that facilitate entry into an established Evans Center ARC
• Fund projects from current ARC investigators that expand a current ARC with an innovative direction
• Fund projects from any investigator that contributes to the development of a new ARC in the following year
Faculty members with primary appointments in the Department of Medicine are eligible to apply for this component. All meritorious applications will be considered across the T1-T4 spectrum.
Any CRC or BMC/BUMC faculty member may apply to this component. Addiction science is a principal research focus of CTSI as supported through partners like the BMC Grayken Center and SPH Alcohol Addiction Center. The CTSI is interested in supporting applications that leverage existing Grayken Center resources, SPH Alcohol Addiction Center resources, or explore new areas in the field of addiction science.
Requirements for Regulatory Approval
The NIH requires that the CTSI obtain explicit approval from the NIH for any CTSI funded pilot with research involving vertebrate animals. IACUC approval documentation and other materials must be submitted to the NIH at least 45 days prior to the project start date. CTSI personnel will work with awardees to meet these requirements for those pilots that are funded with CTSI grant funds.
Application Submittal Process
• A clear translational focus, including a collaboration with a patient-oriented science research team
• Focus on diseases that disproportionately affecting the BU/BMC patient population or ages at the extremes of the lifespan (children and the elderly)
• Approved IRB or IACUC protocols that would permit initiation of research activities as soon as possible
This RFA is open to ALL members of the BMC/BU community and represents a collaborative effort between the CTSI and partner organizations to fund meritorious research applicable to at least one (or more) of the components noted below:
1. CTSI General Funds
2. Community-Engaged Research
3. Bioinformatics/Mobile Health
4. BU School of Medicine (BUSM)
5. Henry M. Goldman School of Dental Medicine (GSDM)
6. Evans Center for Biomedical Research
7. Department of Medicine (DOM)
8. Addiction Science Research
9. New Product/Device Development
CTSI seeks to encourage the development and evaluation of new products, devices, or drug targets that have commercial potential. While CTSI will support applicants at any stage of the development timeline, this mechanism is best suited to early feasibility studies and/or proof of concept. Specific studies could include, but are not limited to, in vitro development, model systems, animal studies, first-in-human testing, or new applications of existing technology. Applicants will be connected to institutional resources to support this process.
Applicants must have a primary faculty appointment at Boston University, and the research to be conducted must be based at Boston University, Boston Medical Center, or any of their affiliated hospitals and health centers. Faculty with co-appointments at BU and BU/BMC affiliated institutions are also encouraged to apply. Please see above for additional eligibility requirements based on the component to which the applicant is applying. In particular, we encourage early investigators to apply. Including those with institutional or individual mentored research awards from NIH or Foundations.
Recipients of previous CTSI awards are eligible to apply for awards to support new research projects, providing awards are at least two years apart.
Individuals from under-represented groups are highly encouraged to apply.
Applications from interdisciplinary teams of investigators are highly encouraged (see below for definition). Collaborations with investigators outside of the BU/BMC and affiliates are allowed, though justification should be provided. To search for BU collaborators, refer to BU Profiles or send a request to the BU CTSI Navigator team at firstname.lastname@example.org.
Two award levels are offered:
The level of funding awarded to successful applicants will be determined after a review of the budget request and budget justification. Funds may be used for any purpose to support the proposed research. Typical expenses include:
Funds may not be allocated to PI or Co-I salary. Awards are not transferable to any other institution (sub-awards are not allowed). Pilot grants are not intended to supplement existing funded awards. Significant overlap in Pilot grant Aims with Aims from a funded grant must be disclosed and justified at the time of submission.
Research Proposed in response to this RFA must be accomplished within the specified award period.
IRB and IACUC Approvals: All IRB and IACUC protocols must be approved prior to the expenditure of any funds.
Delayed Onset Human Subjects Research: The NIH requires that the CTSI obtain explicit approval from the NIH for any CTSI funded pilot with research involving human subjects. Accordingly, the IRB-approved protocol and other materials must be submitted to the NIH at least 45 days prior to the project start date. CTSI personnel will work with awardees to meet these requirements for those pilots that are funded with CTSI grant funds.
Prior Approval of Vertebrate Animals Research:
We strongly advise all Pilot grantees to begin the IRB/IACUC approval process at the time of final grant submission. If you are selected for funding, you will be required to provide your IRB/IACUC approval before funds are released to you.
If at the time of notice of award, you have not submitted your IRB/IACUC application, you will be required to meet with a CTSI IRB/IACUC consultant within 2 weeks and expected to follow a strict timeline for regulatory submission. An award may be rescinded for failure to secure IRB/IACUC approval 3 months after notice of award.
All applications can be submitted here and must include:
Applications will be reviewed by the BU CTSI Scientific Review Committees comprised of faculty with relevant expertise analogous to the NIH review process (with a focus on Significance, Innovation, Approach, and Investigators). Specific review criteria include, but are not limited to:
The CTSI offers an array of research resources in support of research at BU and we strongly encourage CTSI Pilot Grant applications to use these valuable resources. In many cases, leverage of these resources increases the competitiveness of an application. Some examples include the following:
- Regulatory Support
- Grant Writing & Editing, Formatting and Editing Services
- Biostatistics, Data Management & Analysis
- Research Tools
- Study Implementation
- Research Networking
- Consultations – CTSI staff will offer feedback on the feasibility, impact, and design of the proposed scientific investigations
To request a CTSI free service please visit the CTSI Research Navigator Team page here.
If funded, the awardee agrees to submit an online report after the end of the award term indicating key results and any publications, grant applications, funded awards that resulted from the project, new collaborations, and other outcomes. This report must be completed on time if a 2nd stage renewal application is being pursued. Additional abbreviated reports will be requested on an annual basis for 2 years following completion of funding. Any follow on funding depends on prompt and accurate progress reports. Awardees will be contacted regarding the report, once needed. Awardees must acknowledge the CTSI grant in any publication or presentation that arises from data collected through this CTSI funded award, the language provided below is recommended: “This publication [or project] was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Boston University Clinical & Translational Science Institute Grant Number 1UL1TR001430. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.” Awardees are expected to serve on future CTSI Pilot Grant Application Review panels and to provide feedback on the CTSI pilot program. They may be asked to participate in CTSI related symposia or other functions. Awardees may be matched with relevant CTSI functions to support regulatory requirements or completion of proposed Aims and are expected to follow through on suggested timeliness and meetings with CTSI staff. Failure to comply with all post-award requirements jeopardizes eligibility for future Pilot award funding. We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Direct your questions to:
Post Award Requirements
Where to Direct Inquiries
Frederick L. Ruberg, MD
Section of Cardiovascular Medicine, Department of Medicine
Director, Pilot Grant Programs,
Boston University Clinical and Translational Science Institute
Boston University School of Medicine
Boston University Clinical and Translational Science Institute
If funded, the awardee agrees to submit an online report after the end of the award term indicating key results and any publications, grant applications, funded awards that resulted from the project, new collaborations, and other outcomes. This report must be completed on time if a 2nd stage renewal application is being pursued. Additional abbreviated reports will be requested on an annual basis for 2 years following completion of funding. Any follow on funding depends on prompt and accurate progress reports. Awardees will be contacted regarding the report, once needed.
Awardees must acknowledge the CTSI grant in any publication or presentation that arises from data collected through this CTSI funded award, the language provided below is recommended:
“This publication [or project] was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Boston University Clinical & Translational Science Institute Grant Number 1UL1TR001430. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.”
Awardees are expected to serve on future CTSI Pilot Grant Application Review panels and to provide feedback on the CTSI pilot program. They may be asked to participate in CTSI related symposia or other functions. Awardees may be matched with relevant CTSI functions to support regulatory requirements or completion of proposed Aims and are expected to follow through on suggested timeliness and meetings with CTSI staff.
Failure to comply with all post-award requirements jeopardizes eligibility for future Pilot award funding.
We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Direct your questions to:
2022 Integrated Pilot Grant Awardees
Funded by BMC
Pilot Implementation of an Automated and Personalized Risk Prediction Tool of Life Threatening Mass Effect After Middle Cerebral Artery Stroke
The purpose of this current CTSI pilot study is to collect preliminary data on the effect and feedback on an automated email-based risk assessment tool indicating a patient’s risk of developing Life-Threatening Mass Effect after Middle Cerebral Artery stroke in clinical practice. This proposed project builds on existing personalized clinical risk models by examining features that would enable an effective intervention to support clinical decision-making and potentially improve patient care. Such foundational work is instrumental to bridge the gap between model development and successful implementation. This work will provide the preliminary data to study whether a tailored risk prediction tool can improve clinician knowledge and treatment decisions. If successful, they will be poised to develop an innovative framework enabling further investigations of successful strategies that not only predict outcome, but impact patient care by supporting clinical decision making for a variety of disease states.
Meet the Team
Dr. Charlene J. Ong is an Assistant Professor of Neurology and Neurosurgery at Boston University, a lecturer at Harvard Medical School, and a clinical neurointensive care physician at Boston Medical Center. She received her undergraduate degree at University of Pennsylvania, her MD at Columbia University and her Master’s in Population Health Sciences at Washington University School of Medicine. Her research focuses on data-driven tools that support clinical decision making and optimize outcome after acute brain injury. She has received foundational support from the NIH in the form of a K23, the American Brain Foundation, Philips-MIT, the Peter Paul Career Development Committee, and the Clinical and Translational Science Institute at Boston University. Her aim is to become an independent investigator in data-driven strategies to support clinical decision making and optimize outcomes after acute brain injury.
Dr. David Greer is Professor and Chair of the Department of Neurology at Boston University School of Medicine and the Richard B. Slifka Chief of Neurology at Boston Medical Center. Dr. Greer is the editor-in-chief of Seminars in Neurology, and the immediate past editor-in-chief for Neurocritical Care on Call. He has authored more than 300 peer-reviewed manuscripts, reviews, chapters, guidelines and books. His research interests include predicting recovery from coma after cardiac arrest, brain death, and multiple stroke-related topics, including acute stroke treatment, temperature modulation and stroke prevention.
SNAP: Supportive Noninvasive Ventilation for Acute Chest Syndrome Prevention for Hospitalized Children with Sickle Cell Disease
Dr. Cohen’s proposed project, “SNAP: Supportive Noninvasive Ventilation for Acute Chest Syndrome Prevention in Children with Sickle Cell Disease” is a mixed-methods study that is intended to provide preliminary data to support a future NIH application. The study will conduct a multicenter Hybrid Effectiveness/Implementation trial to test the hypothesis that the use of noninvasive, bi-level positive airway pressure (BiPAP) ventilation as supportive care for hospitalized pediatric patients with sickle cell disease is 1) effective at preventing the development and progression of acute chest syndrome (ACS), and 2) feasible to implement across a broad range of institutions. The Department of Pediatrics has been using BiPAP as supportive care on the general pediatrics inpatient unit to prevent ACS since 2017. While BiPAP is a safe and effective treatment for ACS when used in the ICU setting, its use as a preventive therapy – specifically in a non-ICU setting – has never been tested. The proposed pilot study will provide critical information to inform the design of a hybrid intervention trial. (Award co-funded with the BU CTSI)
Meet the Team
Dr. Robyn Cohen is the director of the Division of Pediatric Pulmonary and Allergy at Boston Medical Center and Associate Professor of Pediatrics at Boston University School of Medicine. She went to medical school at the Albert Einstein College of Medicine and did her residency in Social Pediatrics at the Children’s Hospital at Montefiore. She completed her pediatric pulmonary fellowship at Boston Children’s Hospital, then went on to pursue a post-doctoral research fellowship in Respiratory Epidemiology at the Channing Laboratory (now the Channing Division of Network Medicine) at Brigham and Women’s Hospital, which included an MPH in Clinical Effectiveness at the Harvard School of Public Health. Her clinical and research interests are in respiratory health disparities in children with a focus on pediatric asthma and sickle cell lung disease.
Dr. Caitlin Neri is an academic pediatric hematologist at Boston Medical Center (BMC) and Boston University School of Medicine (BUSM) with particular interest in treating children with sickle cell disease, multimodal pain management strategies, and supportive care of children with sickle cell disease. She clinically cares for patients in BMC’s Pediatric Sickle Cell program and directs the multidisciplinary Pediatric Pain Clinic at BMC. She is also an Assistant Professor of Pediatrics at BUSM, where she directs a second-year medical student course in hematology and is currently overseeing the hematology content for the upcoming BUSM curriculum redesign.
Dr. Elizabeth Klings is an Associate Professor of Medicine and Director of the Pulmonary Hypertension (PH) Center and the Center for Excellence in Sickle Cell Disease (SCD) at Boston University School of Medicine (BUSM)/Boston Medical Center. She received her BA and MD degrees from New York University, completed her training in pulmonary and critical care at BUSM, and joined the faculty in 2000. Her current research interests include understanding the interplay of venous thromboembolism and PH in SCD. Drs. Cohen and Klings have worked together for almost 10 years and collaborated on a project evaluating the frequency of sleep disordered breathing in adult and pediatric patients in SCD (Worsham CT, et al. Am J Hematol 2017;92:E649-E651.) She is a member of the Medical and Research Advisory Council of the Sickle Cell Disease Association of America and has helped to craft the US-based response to the pandemic. Her research helped to identify the link between COVID-19 and acute chest syndrome (ACS) in SCD. She led the American Thoracic Society (ATS) sponsored Clinical Guidelines for the Diagnosis and Treatment of PH in SCD (AJRCCM 2014) and Workshop for Defining Clinical and Research Priorities in Sickle Cell Lung Disease (Annals of ATS2019). One of the priorities was the need to identify better strategies for prevention of acute chest syndrome, which is a focus of this project.
Toward Noninvasive Imaging Biomarkers of Drug-resistant Epilepsy
The aim is to investigate a novel noninvasive imaging method for the evaluation of blood-brain barrier permeability. Such findings would improve our knowledge about mechanisms of treatment resistance and the care of people with epilepsy. (Award co-funded with the BU CTSI)
Meet the Team
Dr. Myriam Abdennadher is an Assistant Professor of Medicine in the department of neurology at Boston University School of Medicine (BUSM). Sheis a board-certified neurologist, clinical neurophysiologist, and epileptologist, with a focus on drug-resistant epilepsy, neuroimaging of epilepsy, seizure focus localization and epilepsy surgery. Her research focuses on neurophysiologic and brain imaging methods in drug-resistant epilepsy. She is particularly interested in non-invasive MRI methods to better understand drug resistance and to define seizure zone. Her goal is to improve seizure control and quality of life in patients whose seizures don’t respond to medications and who may benefit from surgical treatment.
Dr. Ning Hua is an Assistant Professor of Radiology at Boston University School of Medicine (BUSM). She is an MRI physicist and expert in neuroimaging and cardiovascular imaging. Her current research focuses on using advanced perfusion MRI methods to study vascular dysfunction in brain pathologies. She is particularly interested in the microvascular contribution to epilepsy, Alzheimer’s disease, related neurodegenerations, and the aging brain. Her goal is to develop novel imaging markers for evaluating blood-brain barrier integrity and microcirculation status (permeability, perfusion, flow rate, curvature, etc.) in both clinical and preclinical settings, and ultimately to advance relevant diagnosis and treatments.
Funded by GSDM
Evaluation of Genotype and Phenotype in a New Hypomaturation Type of Human Rare Dental Disease, Amelogenesis Imperfecta
Tooth enamel formation/amelogenesis is under strict genetic control that determines the composition and structure of this highly specialized tissue. Amelogenesis Imperfecta (AI) is a group of human hereditary disorders that cause abnormalities of the quantity and/or quality of enamel. Depending on the AI type, there can be significant oral morbidity. Knowledge of the molecular etiology and mechanisms leading to alteration of the structure and composition of AI enamel remains incomplete. To date, seventeen genes are associated with different forms of AI. It has been shown that the diverse AI phenotypes result from specific allelic and nonallelic genetic mutations affecting the deposition, calcification, and maturation of enamel. Our preliminary study shows that the proband exhibits markedly different hypomaturation AI phenotypes with lack of enamel mineralization contrast to dentin and a wider pulp chamber space. This clinical phenotype is different from the reported hypomaturation AI phenotypes. Therefore, I hypothesize that a new AI gene mutation in the patient family produces markedly different phenotypes through different mechanisms. There are two specific aims to test this hypothesis: 1.) evaluate phenotype and genotype in the family, and 2.) characterization of enamel in the family. This pilot, an exploratory, patient-oriented research project, will allow correlation of the phenotype-genotype of the AI, thereby allowing improved diagnoses and understanding of this difficult-to-restore/treat and devastating disease, as well as provide new knowledge of enamel formation critical for efforts directed at improving the traditional dental treatment. (Award co-funded with the BU CTSI)
Dr. Yoshiyuki Mochida is a Clinical Associate Professor of Molecular and Cell Biology at Boston University Henry Goldman School of Dental Medicine. He is a dentist – scientist whose career has been devoted to understanding and advocacy of rare dental /craniofacial diseases. He served on several NIH-, private-foundation-, and university-funded projects investigating rare dental conditions including Dentinogenesis Imperfecta, Amelogenesis Imperfecta and Ectodermal Dysplasia. He also actively help the patient support group of the families with rare dental conditions in Massachusetts. The current MA state law does not mandate the insurance companies to cover the out-of-pocket dental treatment expense for these genetic conditions although these patients suffer from genetic diseases and the treatments are medically necessary. This CTSI Pilot Award will allow correlation of the phenotype-genotype of a potentially new type of Amelogenesis Imperfecta, thereby allowing improved diagnoses and understanding of this difficult-to-restore/treat and devastating disease, as well as provide new knowledge of tooth enamel formation critical for efforts directed at improving the traditional dental treatment.
Funded by DOM
Characterizing Care Coordination in Pulmonary Hypertension: A Qualitative Study
Pulmonary hypertension (PH) is a complex disease of the pulmonary vasculature that often requires a multidisciplinary approach to care. Care for certain high-risk PH groups also requires timely referrals from community-based settings to PH specialty care centers (SCCs), referrals that often cross healthcare systems. While engaging specialists may increase expertise in PH management, it may also result in care fragmentation and the attendant risk of duplicative or missed tests or treatments, higher costs, and worse clinical outcomes. Indeed, we have previously shown that patients with PH often receive their diagnosis and treatment in discordant locations across healthcare systems. Effective care coordination is key to reaping the benefits of specialist expertise while mitigating harms associated with care fragmentation. Achieving this important objective in PH first requires a sound understanding of the broad range of factors that influence care coordination across multiple levels. In this qualitative study of providers and patients, we will identify local contextual factors that enable or impede care coordination at the patient, provider, and health system level. When integrated with quantitative social network science results (to be conducted in parallel), these findings will lay the groundwork for the next stage of our research, in which we will develop and test an evidence-informed intervention to improve PH care coordination among multidisciplinary teams and across healthcare systems.
Meet the Team
Dr. Kari R. Gillmeyer is an Assistant Professor of Medicine at Boston University School of Medicine. She is a pulmonary and critical care physician and health services researcher whose work focuses on improving care delivery, quality of care, and outcomes for patients living with PH. Her NIH and foundation funded research utilizes quantitative, qualitative, and mixed method approaches to investigate a wide range of topics within the field of PH, such as drivers and outcomes of guideline-discordant PH care, limitations of administrative data sources in PH research, and prevalence and effects of multisystem PH care. This body of work has identified significant gaps in our understanding of pulmonary hypertension care delivery, including how care is organized and coordinated across the U.S. Her prior research serves as the motivation for this CTSI Pilot Award.
Dr. Renda Soylemez Wiener is a Professor of Medicine at Boston University School of Medicine. She is a pulmonary and critical care physician, health services researcher, and implementation scientist. The goal of her research is to improve communication and decision- making between patients and clinicians, de-implement low value, potentially harmful practices, and implement patient-centered programs. She applies mixed methods to approach complex research questions from multiple angles and has experience conducting quantitative analyses of administrative databases, qualitative analysis, survey research, and evaluations of implementation. Her work has been highly influential; she has published 5 articles that are in the top 1% of most highly cited papers in the field of clinical medicine (per Web of Science) and has an overall h-index of 38, with over 8000 citations to her work (per Google Scholar). She brings extensive, relevant content and methodological expertise to this multidisciplinary CTSI Pilot Award.
Dr. A. Rani Elwy is an Associate Professor at the Warren Alpert Medical School of Brown University in the Department of Psychiatry and Human Behavior, and Adjunct Associate Professor of Boston University School of Public Health in the Department of Health Law,Policy, and Management. She is a renowned expert in mixed methods research, stakeholder engagement methods, and implementation science. Her work focuses on building stakeholder and leadership buy-in for national policy implementation across large integrated healthcare systems; evaluating and disseminating evidence-based complementary and integrative health therapies to treat PTSD, depression, and chronic pain; social network analysis; and implementation outcome assessment. With this expertise, she will help ensure that findings from this pilot work can directly inform the development of an intervention in the next stage of research.
Dr. Elizabeth S. Klings is an Associate Professor of Medicine and Director of the Pulmonary Hypertension Center and the Center for Excellence in Sickle Cell Disease (SCD), caring for over 500 adult and pediatric patients, at Boston University School of Medicine/Boston Medical Center. Her NIH and foundation funded research has helped to define the clinical problem of pulmonary hypertension related to sickle cell disease; she is considered an international expert on the subject. She led the American Thoracic Society sponsored Clinical Guidelines for the Diagnosis and Treatment of PH in SCD (published in the American Journal of Respiratory and Critical Care Medicine in 2014) and Workshop for Defining Clinical and Research Priorities in Sickle Cell Lung Disease (published in the Annals of ATS in 2019). Her current research interests include understanding the role of venous thromboembolism in PH of SCD and improving diagnostic and treatment strategies for patients with PH due to systemic sclerosis. She brings extensive content expertise to this multidisciplinary CTSI Pilot Award.
Dr. Seppo T. Rinne is an Assistant Professor of Medicine at Boston University School of Medicine. He is a pulmonary and critical care physician, clinical informaticist, and health services researcher with a career focused on improving the organization and delivery of care for complex respiratory diseases. Much of his work has focused on improving chronic obstructive pulmonary disease (COPD) management. He has conducted quantitative, qualitative, and mixed- methods research to understand current COPD care practices and to identify improvement opportunities to expand access and improve care quality and coordination. He has previously used positive deviance methods to explore care at high vs. low performing health systems with respect to outcomes for patients with COPD, and identified clear differences in coordinated care across sites, with poor performing sites experiencing barriers to interprofessional relationships and communication. His body of work provides a framework for this pilot work examining care coordination in PH.
This CTSI pilot grant, building on recent preliminary findings of activated receptors on hematopoietic stem cells affected by the JAK2V617F mutation, focuses on novel therapeutic approaches to reducing the burden of the malignant clone in primary myelofibrosis. This project will be the crucial first step in the pursuit of translational application of this research program.
Meet the Team
Dr. Shinobu Matsuura earned her degree as a Doctor of Veterinary Medicine (DVM) from the University of São Paulo, and her PhD from the University of Tokyo, under the guidance of Prof. Hajime Tsujimoto. As an F32 fellow, she received post-doctoral training at the University of California, San Diego, at the laboratory of Dr. Dong-Er Zhang. She joined the laboratory of Dr. Katya Ravid at Boston University as a post-doctoral fellow, joining the Faculty ranks at the Cardiovascular Section/Department of Medicine as an Instructor, and was promoted to Assistant Professor in 2021. She is supported by the SERCA K01 award from the NIH/DCM/ORIP, designed to encourage veterinarians to pursue careers as independent biomedical researchers. She was driven to a career in research by the prospect of developing lifesaving treatments for hematological malignancies. Guided by a fascination with the potential of hematopoietic stem cells, her research goal is to harness the knowledge of stem cell biology to develop impactful therapies for hematological malignancies.
Dr. Katya Ravid,
Barbara E. Corkey Professor of Medicine, and Professor of Biochemistry, Biology and Health Sciences is the founding director of the Evans Center for Interdisciplinary Biomedical Research (ECIBR) and of a university-wide Interdisciplinary Biomedical Research Office (BU IBRO). She is also the Director of the Team Science Program within BU CTSI. Through her leadership roles, she developed platforms for cross-campus interdisciplinary biomedical research- the Affinity Research Collaboratives (ARCs), with documented success at discovery, publications and grant seeking levels. Dr. Ravid is also the founder and past Scientific Director of the BU Transgenic/Knockout Core, the director of an NHLBI-funded training program in Cardiovascular Biology, and the developer and current director of an interdisciplinary Master of Science program in Biological Core Technologies. While leading university initiatives and continuing teaching responsibilities, Dr. Ravid has maintained a creative research program continuously funded by NIH, the American Heart Association (AHA) and Biotech. Her pioneering work, along with that of nearly 50 pre- and post-docs and junior faculty she has guided and mentored, led to recognized discoveries in the fields of hematopoiesis and platelet/vascular biology. With her work being recognized nationally and internationally, Dr. Ravid has been the recipient of several awards such as the prestigious Fulbright Research Scholar Award, the AHA Established Investigator Award, the University of Sidney International Scholarship Award, the Weizmann Institute Professorship Visiting Award, the Robert Dawson Evans Teaching Award and the Educator of the Year Award in Graduate Medical Sciences, among other recognitions. She has served on several national and international review panels, and chaired scientific sessions such as the Gordon Research Conference on Megakaryocyte and Platelet Cell Biology.
Impact of IgA and IgM upon Nasal Microbiota in Common Variable Immunodeficiency
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. Respiratory ailments are the most frequent complications of CVID, with chronic pulmonary disease developing in 30-60% and even more experiencing frequent acute respiratory infections. This project aims to establish cutting-edge approaches to study pulmonary biology in CVID and apply novel bioinformatics strategies in these patients to study complex interactions among microbes and host cells directly in the respiratory tract. This will include evaluating several ways to sample gene expression in the respiratory tract and apply cutting-edge computational approaches to analyzing the complex data derived from these approaches.
Meet the Team
Dr. Paul J. Maglione is a physician-scientist in the Pulmonary Center of Boston University School of Medicine. Dr. Maglione studies human B cell biology, particularly in how it relates to and is informed by primary immunodeficiency disorders. His research program utilizes high throughput strategies such as RNA sequencing, B cell receptor repertoire analysis, and seromics together with cell culture, immunofluorescence, and information from the patient medical record to conduct bedside-to-bench studies on immunodeficiency disorders. In addition to running a research laboratory, Dr. Maglione provides clinical care for patients with immunodeficiency disorders and has particular interest and expertise in common variable immunodeficiency (CVID) and its related complications, including chronic lung disease.
Dr. Evan W. Johnson is an Associate Professor and Associate Chief of the Division of Computational Biomedicine in the Department of Medicine at Boston University. His research team has a longstanding history of applying genetics, genomics, and metagenomics data to solve problems in precision cancer therapy, infectious diseases/host response, and addiction research. His work includes a balance between statistical methods development, algorithm optimization, software development, and clinical application. Statistical innovation in his group focuses on the development of clinically motivated tools that integrate linear modeling, Bayesian methods, factor analysis and structural equations models, Hidden Markov Models, mixture models, dynamic programming, and high-performance parallel computing. This work has resulted in widely used tools and algorithms for profiling transcription factors, preprocessing and integrating of genomic data, aligning sequencing reads, developing multi-gene biomarker signatures (ASSIGN, TBSignatureProfiler), and metagenomic profiling (PathoScope, animalcules). He has successfully applied his tools and methods in the context of pathogen detection, pathway profiling of host and microbial communities, and studying host/pathogen interactions in various contexts including human nutrition, food-borne pathogens, human respiratory diseases, vector- borne pathogen biosurveillance, and in chronic conditions such as cancer and obesity. His laboratory is committed to promote diversity and enhance the training of scientists from all over the globe, and his research includes explorations in the Black Women’s Health Study and international research in the microbiome and host transcriptomics in developing countries such as Brazil, Uganda, Zambia, and India.
Novel Urinary Acute Kidney Injury (AKI) Diagnostic for Cardiothoracic Surgery Patients
In collaboration with Dr. Niloo M. Edwards, they will assess the sensitivity and specificity of urinary nucleophosmin (NPM) and phosphorylated-NPM (p-NPM) as non-invasive markers of renal damage in BMC patients undergoing cardiac surgery at high risk for acute kidney injury (AKI)
Dr. Steven C. Borkan is an Associate Professor of Medicine and Co-Director of the MD-PhD Training Program at Boston University School of Medicine, and an attending physician in the Renal Section at Boston Medical Center. His interests include education of medical students and house staff, basic research on the cellular mechanisms of acute kidney injury (AKI), and the care of underserved patients with renal disease. Dr. Borkan is the senior author of numerous publications in the pathobiology of renal cell injury during AKI and a NIH-funded Principal Investigator. He hopes to harness insights into the pathogenesis of regulated cell death to detect and ultimately treat ischemic acute kidney injury in cardiac surgery patients at high risk for this devastating complication.
Funded by CTSI
Allostatic Load and Physical Activity as Modulators of Racial Disparities in Neurocognitive Aging in the Framingham Heart Study Cohort
Utilizing the Framingham Heart Study Brain Aging Program dataset, the goal of the CTSI pilot grant award is to examine whether racial disparities in allostatic load, the physiological ‘wear and tear’ of the body in response to chronic stress, can account for racial disparities in neurocognitive aging between Black and White older adults and whether physical activity can attenuate these neurocognitive disparities by lowering allostatic load.
Dr. Karin Schon is a cognitive neuroscientist and Assistant Professor at the Department of Anatomy & Neurobiology. She received her Ph.D. in Psychology from Boston University in 2005 and her undergraduate degree in psychology from the University of Hamburg in Germany. She is a past recipient of a K99/R00 Pathway to Independence Award from the National Institute on Aging. Dr. Schon’s research focuses on modulators of the medial temporal hippocampal memory system, including exercise, psychosocial and physiological stress, and aging. Her most recent research examines the impact of racism burden on brain and mental health across the lifespan in Black Americans.
A Prospective Mixed Methods Study of Maternal and Child Well-being and Risk of Relapse in the First Year Postpartum
The year after delivery is a vulnerable period for maternal-infant dyads in substance use recovery. Short and long-term risks include relapse, overdose, death, family dissolution and trauma. In particular, the late postpartum period represents a critical time with high rates of pharmacotherapy discontinuation by 6 months postpartum and the highest overdose rates 7–12 months after delivery. Longitudinal supports and interventions tailored to women and children in the first year postpartum are needed to address high rates of relapse and to promote dyadic well– being. The overarching goal of the First Year Study is to track the experiences of mothers in recovery and their young children in order to identify short- and long-term risk and resiliency factors for further longitudinal study and intervention development. This pilot work will be conducted in partnership with the SOFAR (Supporting Our Families through Addiction and Recovery) Clinic, an innovative, multidisciplinary primary care program built around the needs of substance-exposed infants and their parents in recovery.
Meet the Team
Dr. Mei A. Elansary is an Assistant Professor of Pediatrics at Boston University School of Medicine. Dr. Elansary has special interests in the evaluation and treatment of children with concerns about behavior and development in the context of maternal adversity. She works as the Developmental Behavioral Pediatrician for the SOFAR (Supporting Our Families through Addiction and Recovery) Program. As an early career researcher, Dr. Elansary is interested
in interventions that mitigate the intergenerational effects of maternal post–traumatic stress on child development. Dr. Elansary received her medical degree from Yale University School of Medicine. She completed pediatrics training at the Boston Combined Residency Program and completed subspeciality training in Developmental and Behavioral Pediatrics at Boston Children’s Hospital prior to joining the faculty at Boston University.
Dr. Ruth Paris is an Associate Professor at Boston University School of Social Work and the Associate Director for Research at the BU Institute for Early Childhood Well-Being. Her program of research focuses on attachment-based interventions for vulnerable families with young children. With support from SAMHSA, DOD, NIH, HRSA and private foundations, she has developed and evaluated multiple interventions implemented in a variety of community settings focused on families experiencing high adversity, including those with substance use and mental health challenges, recent immigrants, and military service members. Dr. Paris’ current and recently completed work includes leading the evaluation of interventions targeting parents with young children affected by trauma and substance misuse. One such intervention, BRIGHT, (Building Resilience through Intervention: Growing Healthier Together) is a therapeutic parenting intervention that has been offered in various substance use treatment programs including family residential treatment and methadone clinics. Dr. Paris is currently testing BRIGHT in a pragmatic randomized controlled trial for pregnant and parenting women with SUD/OUD in a specialized prenatal clinic at Boston Medical Center. She is a graduate of Smith College (MSW) and the University of California, Berkeley (PhD). Dr. Paris maintains an independent clinical practice in Greater Boston working with individuals, couples, and families.
Biomagnetic Measurements of Animal Hearts with Novel Magnetic Sensors
Professor Bishop and Dr. Josh Javor, a postdoc in his lab, recently invented a small, low-cost, low power magnetic sensor with very high sensitivity in the range of low frequency biomagnetic fields. Together they were awarded the Pilot Grant from Boston University’s Clinical and Translational Science Institute (CTSI) to detect the magnetic fields from animal hearts. If successful, their work may lead to the development of a non-contact, radiation-free cardiac diagnostic imaging tool that can increase the confidence of cardiologists during diagnosis and in the safe discharge of patients experiencing chest pain.
Dr. David Bishop is currently the Director of CELL-MET, an NSF ERC, and Head of the Division of Materials Science and Engineering at Boston University. He is also a Professor of Physics, Professor of Mechanical Engineering, Professor of Electrical and Computer Engineering, Professor of Biomedical Engineering and Professor of Materials Science and Engineering at BU. Prior to joining BU, he was the Chief Technology Officer (CTO) and Chief Operating Officer (COO) of Lucent Technologies, Bell Labs. Dr. Bishop graduated from Syracuse University with a B.S. in Physics. He received an M.S. and Ph.D. in Physics from Cornell University. Professor Bishop has over 23,000 citations on published scientific articles, 50 issued patents, and is a member of the National Academy of Inventors and the National Academy of Engineering.
Development and In Vivo Efficacy of Small-Molecule IL-4 Inhibitors
Interleukin-4 (IL-4) is a pleiotropic cytokine and an important regulator of inflammation. When deregulated, IL-4 activity is associated with asthma, allergic inflammation, and contributes to the progression of multiple infectious diseases. The impact of uncontrolled IL-4 activity is particularly evident in asthma, a chronic inflammatory disorder of the lungs that currently impacts 25 million Americans, and is characterized by breathlessness, wheeze and a variable airflow obstruction. The current clinically-approved anti-IL-4 treatment (dupilumab, a biologic) for asthma is an antibody-based inhibitor that binds the cellular receptor, but it is limited to moderate to severe forms of the disease. Small-molecule inhibitors are attractive alternatives to biologics, but identifying effective compounds that inhibit the protein-protein interactions between cytokines and their receptors remains a nascent area of research. Recently, we identified the first IL-4 small-molecule inhibitor. The compound, called Nico-52, displayed single-digit micromolar affinity and exhibited functional disruption of type II IL-4 binding in cells. This molecule serves as a starting point to develop treatments for IL-4-mediated immunological disorders like asthma where disruption of IL-4 signaling can be clinically beneficial. Here, we propose preliminary structural optimization and in vivo evaluation of our lead compound and our improved analogs in models of allergic inflammation in mice.
Meet the Team
Dr. Arturo J. Vegas is a Peter Paul Career Development Professor at Boston University. He is appointed in the Department of Chemistry and has affiliations with the Department of Biomedical Engineering and the Materials Science and Engineering Division. He is a core faculty member of the BU Center for Molecular Discovery, the BU Nanotechnology Innovation Center, the Biological Design Center, and is Co-Director of the Translational Research in Biomaterials Training Program. He has also received a New Innovator Type 1 Diabetes Pathfinder Award from the NIH. Arturo received his BA in Biology from Cornell University and a PhD in Chemistry from Harvard University. Research in the Vegas lab focuses on developing novel tissue-targeted drug delivery systems and new therapies for immunomodulation for cancer, type 1 diabetes, and immune-mediated disorders.
Dr. Felicia Chen is an Assistant Professor of Medicine at Boston University School of Medicine and a pulmonary and critical care physician at Boston Medical Center. Her research interest is to uncover the molecular and cellular mechanisms that regulate lung development, homeostasis, and injury repair. Recently, her projects focused on the impact of vitamin A signaling in airway physiology, smooth muscle phenotype, and lung microbiota interactions. In addition to her clinical and research activities, she is active in the education of predoctoral students, medical residents, and pulmonary and critical care fellows at Boston University and Boston Medical Center. Dr. Chen earned her medical degree from Albany Medical College and completed her residency and fellowship training at Boston University School of Medicine.
Developing Tools for Early Detection and Prevention of Lead Take Home
Lead poisoning in children remains a public health issue nationwide, especially within low- /medium-wage racial/ethnic minority families in construction and environmental justice communities. Construction workers typically are exposed to lead at work and can unintentionally bring lead home to their families (known as lead take–home) exacerbating other lead issues in the home. Identifying lead home issues early is not always possible. Traditional methods include hard-to-collect blood data and time-consuming and expensive lead exposure assessment in homes. Thus, this pilot study proposes to 1) validate an accessible (easy to self- collect/store/analyze), non-invasive biomonitoring method such as XRF analysis of toenail clippings, and 2) validate a 1-page risk assessment screening to predict the potential for lead exposure in the home considering lead take-home. These tools will be tested using data and samples from 60 families of construction workers (n=150) from an ongoing study. The goal of the proposed multidisciplinary translational research pilot study is to validate tools that could be used by social workers, physicians, community groups, and researchers in identifying and addressing concerns early about lead exposure in children, as well as understanding families’ lead take-home prevention education and intervention needs. They are not meant to replace traditional methods but to ensure screening has a wider reach. Specifically, tools could be used in future surveillance efforts within vulnerable communities likely to have a high representation of lead-exposed workers. A refined toenail clippings XRF method could potentially have commercial capabilities by providing instantaneous results in clinical point-of-care testing.
Meet the Team
Dr. Diana M. Cellabos is an Assistant Professor at Boston University School of Public Health. Her life’s passion is to address health disparities by identifying environmental factors that cause disease, injury, or impairment. These factors range from emerging hazards related to new technologies, to known hazards that are transferred to vulnerable populations including workers in small businesses, minorities, and workers in developing economies. Her research aims to better understand health effects from exposure to complex mixtures to uncovering and addressing the disproportionate burden of exposure in vulnerable populations. She is motivated by interdisciplinary and collaborative research projects to understand and prevent health effects of environmental and occupational contaminants in the United States and abroad. She has expertise in the development, coordination and analysis of highly complex environmental and biological sampling techniques, including the development of new sampling methodologies.
Dr. Jennifer Greif Green is an associate professor in special education and a child clinical psychologist. Her research focuses on supporting students with emotional/behavioral disorders and bullying prevention. Within these lines of research, she studies teacher identification of students with mental health needs, racial/ethnic disparities in mental health service access, and youth bullying involvement.
Dr. Noah Buncher is a pediatrician in Primary Care Pediatrics at Boston Medical Center and Assistant Professor of pediatrics at Boston University School of Medicine. His interests are varied and include adverse childhood experiences, refugee medicine, global health, and motivational interviewing. During his residency, he was awarded an AAP CATCH Grant to help establish one of Connecticut’s only dedicated pediatric global health clinics designed to provide culturally sensitive, comprehensive care to newly arrived refugee children, help transition these children to a medical home, and connect refugee families to community resources. Dr. Buncher was a Visiting Resident Scholar with Baylor International Pediatric Aids Initiative, providing clinical care to HIV positive children, adolescents, and their families at Baylor College of Medicine Children’s Foundation – Lesotho.
Disparities in Time to Diagnosis of Ankylosing Spondylitis
The team will use analytic tools developed by Observational Health Data Sciences and Informatics (ODHSI) to study the time to diagnosis among people with ankylosing spondylitis, a condition that is often associated with 6-8 years from the onset of back/joint pain to diagnosis. They will study whether the time to diagnosis varies according to gender, race, or ethnicity. By using Boston Medical Center data in the Observational Medical Outcomes Partnership (OMOP) structure, the team will be able to expand future analyses to other datasets that use the same model.
Meet the Team
Dr. Maureen Dubreuil is a rheumatologist who specializes in spondyloarthritis. Her work focuses on comorbidities and pharmacoepidemiology of spondyloarthritis.
Dr. S. Reza Jafarzadeh is an epidemiologist with a research interest on the application of causal inference methods in observational studies of rheumatic diseases using OHDSI tools and data standards.
Gut health, Micronutrient Status, and Linear Growth Among Infants in Lusaka, Zambia
Undernutrition during the critical window from conception until 2 years increases the risk of mortality. Among the children who survive, it can have lifelong effects on the immune, metabolic and central nervous systems. Globally, 149 million children <5 years are stunted (length/height-for-age z-score [LAZ/HAZ] <-2SD of WHO median), often due to chronic undernutrition. The global COVID-19 pandemic has substantially increased food insecurity and malnutrition, particularly in low- and middle-income countries (LMICs) like Zambia, where 40% of children <5 years were stunted as of 2018. Interventions and research targeting stunting have historically focused on nutrient intake and clinical infections; however, nutrient malabsorption, resulting from poor intestinal health, may also drive stunting even in the context of adequate intake. Gaining a better understanding of the role of intestinal health in child growth will help inform the design of more effective interventions. This study will analyze biospecimens collected during the baseline assessment from a randomized controlled trial (RCT) that will assess the impact of lipid nutrient supplements (LNS) on stunting in Zambia. CTSI funds will support the analysis of serum specimens for biomarkers of environmental enteric dysfunction (EED) and 16S sequencing of rectal swabs to describe the gut microbiome in the infants. Their primary aims are to evaluate the association between biomarkers of EED and the GI microbiome with infant stunting in Zambia.
Meet the Team
Dr. Lindsey M. Locks is an Assistant Professor in the Departments of Health Sciences (Sargent College) and Global Health (School of Public Health). She directs the Sargent College Global Nutrition Lab, and her research focuses on undernutrition in women and children in low- and middle-income countries. Her current research focuses on the role of human milk, micronutrients, infant and young child feeding practices in infant gut health and pediatric growth. She has 15 years of experience in global nutrition research and programs in sub-Saharan Africa and South Asia. She holds a ScD in Nutritional Epidemiology from the Harvard Chan School of Public Health and a MPH in Epidemiology and Global Health from the Columbia University Mailman School of Public Health.
Dr. Peter Rockers is an Associate Professor in the Department of Global Health at the Boston University School of Public Health. He is the Director of the Global Health Program Design, Monitoring & Evaluation certificate within the MPH program. Dr. Rockers’ research is primarily concerned with understanding and improving child development outcomes in low- and middle- income countries. He uses epidemiologic methods to investigate biological and social determinants of child development. He also uses experimental methods to test the impacts of interventions that aim to improve child development. Dr. Rockers is particularly interested in the relationship between poverty and neurodevelopment
Dr. Jacqueline M. Lauer is a Clinical Assistant Professor in the Department of Health Sciences at Boston University. Her research focuses on the environmental contributors to poor growth and development among infants and young children in low-resource settings. She completed a postdoctoral research fellowship at Boston Children’s Hospital where she studied the causes, consequences, and assessment of environmental enteric dysfunction (EED), a subclinical, inflammatory disorder of the small intestine. She completed her PhD in Food Policy and Applied Nutrition from Tufts University’s Friedman School of Nutrition Science and Policy while working as a researcher for USAID’s Feed the Future Innovation Lab for Nutrition in Uganda. She also holds a MPH in International Health and Development and a BSPH from Tulane University.
Impact of APOL1 Renal Risk Variants on Placental Function and Racial Disparities in Preeclampsia Risk
Compared with whites, black pregnant people have a 1.7-fold increased risk of preeclampsia (PE) and are three times more likely to die of PE. They hypothesize that variants in the apolipoprotein L1 (APOL1) gene, a strong risk factor for kidney disease in black individuals, impact the development of the placenta and predispose black birthing people to an increased risk of PE. Epidemiological studies have shown the fetal/placental APOL1 genotype to be associated with increased PE risk. The goal of this proposal is to elucidate the effects of APOL1 variants on placental invasion and function by 1) defining the expression patterns of APOL1 in placental compartments over gestation, and 2) assessing the effect of APOL1 variants on trophoblast function through gene overexpression studies in trophoblast cell lines. Ultimately, delineating the impact of APOL1 variants on placental development may provide new insights into the complex pathophysiology of PE among black pregnant people and may identify novel therapeutic targets.
Meet the Team
Dr. Wendy Kuohung is the Division Director of Reproductive Endocrinology and Infertility at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at Boston University School of Medicine. Dr. Kuohung received her medical degree from the Yale University School of Medicine. She completed her Obstetrics and Gynecology residency training at Boston Medical Center and fellowship training in Reproductive Endocrinology and Infertility at Brigham and Women’s Hospital. Dr. Kuohung’s research interests are focused on placental development, infections of the reproductive tract, and reproductive health care disparities. She also has clinical expertise in advanced minimally invasive and robotic gynecologic surgery, female infertility, and fertility preservation. Dr. Kuohung was a former Reproductive Scientist Development Program Scholar and has served as PI on a number of NIH and pharmaceutical research grants since 2003.
Dr. Nader Rahimi is a molecular biologist and currently an Associate Professor at the Department of Pathology and Laboratory Medicine at Boston University. Nader Rahimi has extensively published in the field of signal transduction by receptor tyrosine kinases in particular VEGF receptor tyrosine kinases. His notable works include the demonstration of the differential function of VEGFR-1 and VEGFR-2 in angiogenesis, identification of lysine methylation as a novel mechanism of activation of VEGFR-2, and establishing protein ubiquitination as a major pathway modulating the angiogenic signaling of VEGFR-2. He is also responsible for the discovery of multiple cell surface receptors including, IGPR-1 (TMIGD2), TMIGD1, MINAR1, and MINAR2. His recent work on COVID-19 resulted in the discovery of CD209L and CD209 as novel receptors and vimentin as an attachment factor for SARS-CoV-2.
Inverse Spectroscopic Optical Coherence Tomography for the Detection of Corneal Ultra-Structural Changes in keratoconus and Quantification of Corneal Cross-linking
Keratoconus is a progressive condition characterized by thinning and steepening of the corneas, leading to significant vision loss generally by the 2nd to 3rd decade of life. Corneal cross-linking (CXL) is a surgical treatment used to stiffen the cornea to prevent further progression, and results in the cross-linking of collagen fibrils and increased collagen fiber diameter. Despite the advent of CXL for this previously inexorable disease, primary clinical challenges include the inability to immediately evaluate the efficacy of CXL, which fails up to 20% of the time, as well as selecting appropriate CXL candidates prior to additional disease progression. They propose to address these challenges by using a novel imaging method, inverse spectroscopic optical coherence tomography (ISOCT), to detect and quantify corneal ultra-structural changes after CXL, as well as to detect native ultra-structural differences in keratoconus. The advantages of ISOCT are its super sensitivity to nanoscopic tissue changes achieved through spectral sensing, its rapid imaging speed (~4s per scan), and its ability to create a 3D map over a large field of view (~5x5x2 mm3). ISOCT can measure collagen cross-linking in vitro, and preliminary data suggests ISOCT can detect changes one month after CXL in keratoconus patient eyes, as well as between normal and keratoconus corneas. Their specific aims are to validate that ISOCT can quantify CXL-associated changes in vivo, including immediately after treatment, and also determine whether ISOCT markers correlate with increasing severity or instability of keratoconus. ISOCT has the potential to be a valuable new clinical tool.
Meet the Team
Dr. Hyunjoo Lee is a board-certified ophthalmologist, with fellowship training in cornea, external disease and refractive surgery. As a current attending ophthalmologist at Boston Medical Center and Boston University Eye Associates, and the director of the cornea service, she cares for patients with a variety of corneal and ocular surface conditions, including many patients with keratoconus, a progressive disease of the cornea that can lead to profound vision loss. She is an experienced corneal surgeon, performing corneal cross-linking to treat keratoconus, laser vision correction, cataract surgery, and all types of corneal transplantation.
Dr. Lee has been actively involved in clinical and translational research, including as a lead co- investigator in a randomized, double-masked, clinical trial to compare oral sedation to intravenous sedation for ocular procedures, and is the site PI for multiple clinical trials. She holds numerous approved IRB applications, including for the study of using novel optical coherence tomography techniques for imaging the cornea and ocular surface. A significant focus of her research has been in imaging modalities that can aid in the diagnosis of corneal and ocular surface conditions. She has presented work on imaging of ocular surface squamous neoplasia and keratoconus at multiple Association for Research in Vision and Ophthalmology (ARVO) meetings. She has received both an NIH CTSI pilot grant through Boston University School of Medicine as the principal investigator (PI), and an NIH R21 grant as a co-PI for studying the application of inverse-spectroscopic optical coherence tomography and two-photon autofluorescence imaging to the differential diagnosis of ocular mucosal pathologies, in collaboration with bio-engineer Dr. Ji Yi of the Department of Bioengineering at Johns Hopkins University, which has led to the publication of their novel findings. Dr. Lee and Dr. Yi are now pursuing the application of this novel imaging technology to the diagnosis and treatment of keratoconus.
Dr. Ji Yi is an Assistant Professor of Medicine at BU School of Medicine. He completed his undergraduate and PhD degrees in biomedical engineering at Tsinghua University in 2005 and Northwestern University in 2012, respectively. He started independent research at Boston University in 2015 and transitioned to Johns Hopkins University’s Department of Biomedical Engineering and Ophthalmology in 2020. He specializes in optical imaging, in particular developing multimodal volumetric microscopy across large length scales of biological systems. His PhD research is focused on early gastroenterology (GI) cancer detection using light scattering; he started ophthalmic imaging in his postdoc training. He has made several impactful technical innovations including inverse spectroscopic optical coherence tomography, visible light OCT, and oblique scanning laser ophthalmoscopy. He has contributed over 60 peer-reviewed journal articles, and is the co-inventor on 6 US and international patents. He is leading and participating in several NIH-funded studies. He has received numerous early career awards including Baxter Young Investigator Award (2013), JDRF Postdoctoral Fellowship (2014), BrightFocus Foundation awards (glaucoma national award in 2017, macular degeneration award in 2018), Boston University KL2 Career Development Award (2017) and Boston University Evans Junior Faculty Research Merit Award (2018).
Modeling Developmental Alterations Linked to Congenital Hydrocephalus Using Zebrafish
Congenital hydrocephalus is a frequent neurodevelopmental disorder (~1:1,000 births) caused by alterations in the function of the brain ventricular system. It is a major cause of child mortality and morbidity, representing up to 3% of all pediatric hospital charges. The standard treatment for congenital hydrocephalus, shunt implantation, has been the same for over 60 years and remains associated with a high risk of failure. Sequencing efforts have revealed genetic mutations in patients with inherited congenital hydrocephalus, but the mechanisms by which dysfunctions of these genes affect development and function of the brain ventricular system remain largely unknown. They propose to generate a collection of zebrafish mutant lines carrying mutations in genes linked to congenital hydrocephalus to define the developmental defects in the brain ventricular system associated with the disease. Zebrafish embryos are optically clear; it allows the direct visualization of the entire development of the brain ventricular system, which is not possible in other vertebrate organisms. They anticipate that this collection of zebrafish mutant lines will serve as a valuable resource to define the biology underlying congenital hydrocephalus and find new cures.
Dr. Arthur Marivin is a Research Assistant Professor in the Department of Biochemistry at Boston University School of Medicine. He received his Ph.D. at the University of Burgundy in Dijon, France. Dr. Marivin’s research focuses on characterizing novel principles of G-protein signaling and defining their role in disease. His previous work as a postdoc in the Garcia-Marcos lab (Department of Biochemistry) uncovered how alterations in G-protein signaling networks cause cancer or birth defects that include congenital hydrocephalus. His research combines dissection of signaling circuits using in vitro biochemistry and synthetic biology tools with disease modeling in vivo using Xenopus and zebrafish embryos.
Multiomic Phenotyping in Cardiac and Skeletal Muscle in Heart Failure with Preserved Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF) is the result of a complex interplay of multiple comorbidities. Mitochondrial dysfunction and metabolic disturbances are present in both myocardial and skeletal muscle beds in models of HFpEF. However, the omics approaches for identifying unique signatures in HFpEF have predominantly targeted circulating blood or single-chamber biopsy sites and are performed in isolation, inadequately capturing the opportunity to deeply characterize tissue relevant to HFpEF pathogenesis to identify novel pathways for targeted interventions. To address these gaps, we propose to leverage an active collaboration with cardiac pathologists and a well-established rapid autopsy pathology program, to characterize the cardiac and skeletal muscle phenotype of individuals with and without HFpEF. This BU CTSI proposal is aimed at utilizing multiomics of cardiac and skeletal muscle tissue in human HFpEF to evaluate the relations of the molecular interactome across tissues and to identify novel therapeutic targets and interventions. This application leverages existing multidisciplinary collaborations to fund preliminary data to strengthen a multi-PI R01 grant submission.
Dr. Deepa M. Gopal
Assistant Professor of Medicine, Cardiovascular Division
She is a clinician-investigator whose research focuses on developing a phenotyping strategy to identify early heart failure (HF) with preserved ejection fraction (HFpEF) in individuals with obesity. This strategy will help direct mechanistically-driven therapeutics earlier in an individual’s HF disease trajectory to mitigate risk. This research harnesses her clinical expertise using novel cardiac deformation imaging in echocardiography, invasive and non-invasive cardiopulmonary exercise testing, and circulating/tissue biomarkers as key components of her methodology.
Dr. Jessica L. Fetterman
Assistant Professor of Medicine in the Whitaker Cardiovascular Institute
She is a basic and translational scientist in cardiovascular pathophysiology. Her research program utilizes trans-disciplinary approaches to advance their understanding of the role and mechanisms of mitochondrial genetics in cardiovascular pathophysiology. To do so, they evaluate mitochondrial genetics and biology at the population level through genetic epidemiology and systems biology approaches, at the cardiovascular tissue level through rapid autopsy samples and biopsies, and through the creation of cardiovascular cells from human induced pluripotent stem cells. They are creating a number of software packages aimed at enhancing their ability to delineate pathogenic and benign mitochondrial genetic variants and to enable the investigation of mitochondrial-nuclear genetic interactions. Their goal is to identify the mechanisms for how mitochondrial genetic variation contributes to the development of cardiovascular diseases.
Soft Micro Robotic Needle Steering Mechanisms for Interventional Bronchoscopy
Lung cancer remains the leading cause of death from cancer in the U.S. Early diagnosis is
of paramount importance to increase the survival rate of lung cancer and can only be achieved via accurate tissue sampling. This is particularly challenging while navigating in the deep locations of the lungs, where the angles of the various takeoffs of the bronchi can be difficult to access and cancer can remain undetected. Robotic platforms for interventional bronchoscopy, currently available on the market, lack distal dexterity and the capability to achieve sharp turns. This pilot grant will focus on novel robotic actuation mechanisms to steer the tip of biopsy tools and enable tissue sampling in difficult to reach areas of the lung.
Meet the Team
Dr. Sheila Russo is an Assistant Professor in the Department of Mechanical Engineering and the Division of Materials Science and Engineering at Boston University. She completed her Ph.D. degree at the BioRobotics Institute, Sant’Anna School of Advanced Studies (Italy) and her postdoctoral training at the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. She is the founder and director of the Material Robotics Laboratory at BU that focuses on design, mechanics, and manufacturing of novel multi-scale and multi-material biomedical robotic systems. Her research interests include medical and surgical robotics, soft robotics, sensing and actuation, meso- and micro-scale manufacturing techniques, and advanced materials.
Dr. Ehab Billatos is an Assistant Professor of Medicine at Boston University Medical Center specializing in pulmonary and critical care. He serves as the Director of Inpatient Pulmonary Clinical Services, the Director of the Pleural Disease Service, and the Assistant Director of Bronchoscopy at Boston University Medical Center. He has a special interest in advanced bronchoscopic techniques for diagnosis of lung cancer. He also serves as the Principal Investigator for the DECAMP consortium (Detection of Early Cancer Among Military Personnel) which aims to improve the early diagnosis of lung cancer via biomarker validation and development from minimally invasive specimens. This is a multi-center trial sponsored by the Department of Defense, the National Cancer Institute, Johnson & Johnson, and NovartisPharmaceuticals.
2021 Integrated Pilot Grant Awardees
A Patient-Specific Induced Pluripotent Stem Cell (iPSC)-based Organoid Model of Pulmonary Fibrosis
The incompletely understood pathogenesis of pulmonary fibrosis and lack of reliable preclinical disease models have been major hurdles in developing effective therapies. Emerging literature now implicates alveolar type 2 (AT2) cell dysfunction as an initiating pathogenic event in the onset of a variety of pulmonary fibrosis syndromes, including adult idiopathic pulmonary fibrosis (IPF) and childhood interstitial lung disease (chILD). However, the inability to access primary AT2 cells from patients, particularly at early disease stages, has impeded the identification of disease-initiating mechanisms. The goal of this proposal is to provide a patient-specific in vitro model system, based on induced pluripotent stem cell-derived AT2 cells that we have engineered in vitro from patients with pulmonary fibrosis associated with the most common disease-associated SFTPC variant (SFTPCI73T), in order to uncover the mechanisms leading to human AT2 cell dysfunction, at the moment of disease inception.
Dr. Konstantinos-Dionysios Alysandratos obtained his medical degree and doctoral degree in Immunopharmacology from the University of Athens in Greece. He completed his internal medicine residency training at the University of Texas Southwestern and Parkland Medical Center in Dallas, TX. Followingly, he pursued clinical fellowships in Sleep Medicine and Pulmonary/Critical Care Medicine at Boston University Medical School and Boston Medical Center. During his fellowship training, he joined Dr. Darrell Kotton’s laboratory at the Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center. He is currently an Assistant Professor of Medicine at Boston University School of Medicine.
His current research aims to expand our scant knowledge of the pathogenesis of common lung diseases such as interstitial lung disease (ILD) and specifically the role of alveolar type 2 (AT2) cells at the inception of disease. Under the mentorship of Dr. Darrell Kotton, he has developed an in vitro model system that permits investigation of epithelial-intrinsic events that lead to AT2 cell dysfunction over time using patient-derived cells that carry a disease-associated variant, SFTPCI73T, known to be expressed exclusively in AT2 cells.
Dr. Alysandratos has received several honors and awards throughout his career including from the American Thoracic Society and the American Lung Association. While in residency training, he was voted as an honorary member of the Alpha Omega Alpha Medical Honor Society by the university’s academic community. Most recently, Dr. Alysandratos received the Pulmonary Fibrosis Foundation I.M. Rosenzweig Junior Investigator Award for his innovative research on stem cell-based models of pulmonary fibrosis.
Culturally-Adapted Motivational Interviewing and Contingency Management for Reducing Illicit Stimulant Use in Black and Latin People
This CTSI pilot study is preliminary work in attempting to combine three approaches to treating stimulant use disorder in Black and Latinx people: 1) culturally adapted motivational interviewing; 2) recovery coaching; and 3) contingency management. We will first conduct focus groups in Black and Latinx people who use stimulants, in order to inform the adaptation of an existing motivational interviewing intervention. We will then pilot test this adapted intervention, which will be delivered by recovery coaches, in a clinic that provides contingency management treatment for stimulant use.
Meet the Team
Dr. Tae Woo (Ted) Park is an Assistant Professor of Psychiatry at Boston University School of Medicine. He is an addiction psychiatrist and researcher. He has a NIDA K23 award that aims to reduce benzodiazepine use in patients who receive opioid agonist treatment. His clinical focus is on the treatment of addiction and its psychiatric comorbidities. He is the medical director of the ABOVE program at Boston Medical Center, a program that focuses on treating co-occurring opioid use and mental disorders, and a consultant for BMC’s CATALYST program for transitional age youth with substance use disorders. In addition, he is active in the education of residents and addiction psychiatry fellows at Boston University/Boston Medical Center. He completed his psychiatry training at Western Psychiatric Institute and Clinic in Pittsburgh, PA, and his postdoctoral research at the Boston VA and Boston University School of Medicine.
Dr. Ricardo Cruz is a primary care physician at Boston Medical Center in the Department of Medicine, Section of General Internal Medicine. He is a graduate of Boston University School of Medicine (BUSM) and the BUSM/Boston Medical Center (BMC) Internal Medicine Residency Primary Care Training Program. He is the Principal Investigator of the Department of Health and Human Services Office of Minority Health funded Project RECOVER (Referral, Engagement, Coaching, Overdose preVention Education in Recovery), a project that utilizes peer recovery coaches to assist with engagement and retention of individuals with opioid use disorder into treatment and primary care services after completion of acute treatment services (detoxification). In addition, he is a Clinician Educator and is part of the Core Faculty of the Internal Medicine Primary Care Training Program at BUSM/BMC. He is in the BUSM Academy of Medical Educators where he teaches medical students during the pre-clinical doctoring courses with a focus on the development of clinical reasoning. He has been a co-investigator on NIAAA and NIDA-funded randomized clinical trials testing medications for alcohol and cocaine use disorders. His interests are in providing primary care and treatment for substance use disorders for vulnerable populations including racial and ethnic minority communities and individuals with a history of criminal justice involvement.
Dr. Christina S. Lee is an associate professor in the School of Social Work at Boston University (BUSSW) and a faculty affiliate at BU’s Center for Antiracist Research. Her research bridges the areas of intervention science, addiction psychology, and health disparities. By focusing on the effects of social and environmental stressors, Dr. Lee has become an influential voice in efforts to reduce risky health behaviors among diverse, understudied groups. She is PI and co-PI on NIH-funded addiction treatment research, affiliate training faculty at the Center for Alcohol and Addiction Studies at Brown University, research core director at the BUSSW Center for Innovation in Social Work and Health, and mentors graduate and postdoctoral scholars from diverse racial-ethnic groups. Dr. Lee is a member of the editorial board of the Journal of Consulting and Clinical Psychology.
Epidemiology COVID-19 Response Corps
In response to the COVID-19 pandemic, Drs. Ellie Murray and Jennifer Weuve created the Epidemiology COVID-19 Response Corps (or COVID Corps for short), which brought together over 150 students, faculty, and alumni to help fill gaps in COVID research and develop messaging tools to help people understand how to stay safe. Our CTSI funded project will conduct an impact evaluation of the COVID Corps so that we can understand what worked well, what didn’t work as well, and what we can do better going forward during this pandemic and in future public health crises.
Dr. Eleanor J. Murray is an Assistant Professor of Epidemiology at Boston University School of Public Health who focuses on improving methods for evidence-based decision-making and human-data interaction. Her work primarily focuses on applications to public health and clinical epidemiology, including applications to HIV, HPV, cancer, cardiovascular disease, psychiatric disorders, musculoskeletal disorders, social and environmental epidemiology, and maternal and adolescent health. Dr. Murray also conducts meta-research evaluating bias in existing research. During the COVID pandemic, Dr. Murray has been working on improving science communication about epidemiology and public health concepts and identifying and addressing barriers to equitable vaccination distribution and acceptance. She completed a postdoctoral research fellowship in Epidemiology at the Harvard T.H. Chan School of Public Health, working on causal inference for comparative effectiveness and real-world evidence in the HSPH Program on Causal Inference. She holds a ScD in Epidemiology and a MSc in Biostatistics from Harvard, an MPH in Epidemiology from Columbia Mailman School of Public Health, and a BSc in Biology from McGill University. Dr. Murray is an Associate Editor for Social Media at the American Journal of Epidemiology and can be reached on Twitter at @EpiEllie
Dr. Jennifer Weuve is an associate professor of epidemiology at the Boston University School of Public Health. In her research, she seeks to identify causes of cognitive decline and dementia, particularly environmental causes. Undergirding this research is her dedication to aligning epidemiologic methods to solving public health problems. She is the PI or co-investigator of several NIH-supported investigations and projects in all of these realms. During the COVID-19 pandemic and with Dr. Ellie Murray, she co-founded the BUSPH Epidemiology COVID-19 Response Corps, which engages with students, faculty, and other BU community members to address important epidemiologic issues related to the COVID-19 pandemic, including research, communication, policy, and best practices. Dr. Weuve earned her master’s in public health degree from the University of Minnesota and her doctoral degree from the Harvard TH Chan School of Public Health.
Generation of a Conditional Mouse Strain for GNB2 to Investigate Legionellosis
In the current CTSI pilot grant, Dr. Bosmann and his co-workers aim to generate a novel floxed mouse strain for tissue-specific gene deletion of the G-protein subunit, GNB2. The conditional knockout mice will later be used to study the role of GNB2 in myeloid cells during Legionella infection of the lung.
Dr. Markus Bosmann is an Associate Professor in the Pulmonary Center, Department of Medicine holding secondary appointments in the Department of Pathology & Laboratory Medicine, BUSM, and the National Emerging Infectious Diseases Laboratories (NEIDL). He graduated as a Doctor of Medicine, with a summa cum laude honor thesis, from the Johann Wolfgang Goethe University, Frankfurt, Germany. He continued his career with residency training in medicine, laboratory medicine, and a research postdoctoral fellowship at the University of Michigan, Ann Arbor, followed by a junior faculty appointment at the Johannes Gutenberg University, Mainz, Germany. His research interests are focused on the cellular and molecular pathogenesis of infection-associated inflammation. The work in his multidisciplinary, diverse research team is centered around understanding the host response to microbial pathogens in the context of lung injury, pneumonia, and sepsis. Dr. Bosmann is also the director of the newly established Affinity Research Collaborative (ARC) named Respiratory Viruses: A Focus on COVID-19. He was awarded the Hugo-Schottmüller prize of the German Sepsis Society in 2020.
HIV-1 RNA Modification as a Driver of Innate Immune Activation
HIV-1+ individuals on successful anti-retroviral therapy still suffer from various complications caused by chronic inflammation, but the mechanism underlying persistent inflammation is currently unclear. We have shown that expression of HIV intron-containing RNA (icRNA) in infected macrophages induces pro-inflammatory responses, however, what makes HIV icRNA immunostimulatory remains unclear. Epitranscriptional modifications in viral RNAs have been linked to various biological processes including innate immune sensing and induction of type I interferon and pro-inflammatory responses. We, therefore, hypothesize that HIV icRNAs are marked by unique base modifications, which confers immune-stimulatory capacity to HIV icRNA. To test this hypothesis, in collaboration with Dr. Daniel Cifuentes, Assistant Professor in the Department of Biochemistry, we will use two complementary approaches to quantify RNA modifications in HIV icRNA: 2D thin-layer chromatography (TLC) and nanopore sequencing (Oxford Nanopore Technologies). We will determine the quantity and position of RNA modifications in HIV icRNAs. We hope that the successful completion of this proposal will serve as a basis for a future NIH R01 grant that will focus on the roles of HIV RNA modification in innate immune responses. Ultimately, identification of HIV RNA modifications responsible for immune activation could lead to the development of novel therapeutic strategies to manage inflammation-associated complications in HIV+ individuals on anti-retroviral therapy.
Meet the Team
Dr. Hisashi Akiyama received his Ph.D. from Kyoto University, Japan. He performed his postdoctoral research at the University of Heidelberg in Germany where he worked on cellular and molecular mechanisms of HIV replication. He is currently a Research Assistant Professor in the Department of Microbiology at Boston University School of Medicine. His research goal is to understand the pathogenesis of HIV. In particular, he is interested in the role of myeloid cells in the establishment and dissemination of HIV infection and mechanisms of virus evasion from innate and adaptive host immune responses.
Dr. Daniel Cifuentes is an Assistant Professor in the Department of Biochemistry at the Boston University School of Medicine. Dr. Cifuentes received his Ph.D. from the University of Barcelona, Spain, for his studies in metabolic regulation. He completed his postdoctoral training in the Department of Genetics at Yale University School of Medicine, where he specialized in microRNA biology and vertebrate embryogenesis. His research goals at Boston University combine high-throughput genetic, genomic, and proteomic approaches to address fundamental questions of RNA regulation in viral and vertebrate systems.
Highly Multiplexed Immunophenotyping of Aggressive Histologic Patterns of Early-Stage Lung Adenocarcinomas
Lung cancer remains the leading cause of cancer death, in large part due to our inability to intercept the disease process prior to progression to an advanced and lethal state. We lack an understanding of the earliest targetable molecular events in lung carcinogenesis and effective strategies to identify and treat aggressive cancers. Using single-cell proteomics, via imaging mass cytometry (IMC) we will study immune cell marker expression and localization in normal tissue and adjacent LUAD with either aggressive or indolent histologic patterns that may identify biomarkers to predict the presence of aggressive cancers. The proposed study leverages a unique set of early-stage LUAD tumors with extensive pathologic characterization that may start to unravel aggressive LUAD immune changes, which has implications for lung cancer diagnosis and interception. The results of this work may suggest new lung cancer interception strategies for early-stage invasive LUAD as well as improve current clinical management and outcomes. Our findings will serve as pilot data for a planned NIH R01 proposal.
Meet the Team
Dr. Sarah A. Mazzilli is an Assistant Professor of Medicine at Boston University School of Medicine in the section of Computational Biomedicine. Sarah earned her Ph.D. in Molecular Pharmacology & Therapeutics at Roswell Park Comprehensive Cancer Center (SUNY Buffalo followed by a postdoctoral fellowship at Boston University with Dr. Avrum Spira. In her short time on faculty, she has established her research laboratory where her group is investigating the molecular events associated with the progression of premalignant lung lesions to identify novel chemoprevention strategies. Sarah’s group has a particular interest in characterizing clinical samples from pre-cancerous lung lesions as part of the Lung Pre-Cancer Atlas (PCA) part of the NCI- Human Tumor Atlas, which aims to enable the discovery of novel epithelial and immune modulations that are involved in the progression premalignant lesions to frank carcinoma to identify mechanisms to intercept the disease process. This pilot study will be an extension of that work and will take advantage of a new technology, Image Mass Cytometry, brought to BU through sponsored research programs, which her research team hopes this pilot will bring new opportunities for future NIH/NCI R01 funding in collaboration with her co-investigators.
Dr. Jennifer Beane is an Assistant Professor of Medicine at Boston University School of Medicine in the section of Computational Biomedicine. Jennifer earned her Ph.D. in Bioinformatics at Boston University, where she remained for her postdoctoral work. Jennifer joined the BU faculty in 2011 where her research interests focus on developing and implementing computational and statistical methodologies to expand our knowledge of the molecular changes that occur in the airway field on injury associated with smoking and lung cancer. Towards this goal, her research group has leveraged bulk and single-cell transcription data and to identify gene expression changes associated with smoking, lung cancer premalignancy, and lung cancer to develop clinically relevant biomarkers and new lung cancer interception therapies. Jennifer’s expertise in lung biology and informatics is well suited to lead the analysis of this pilot study and to establish analysis pipelines for image mass cytometry data that can be adopted for future funded applications.
Dr. Eric Burks is a Clinical Associate Professor of Pathology at the Boston University School of Medicine and the Medical Director for Hematopathology and Immunohistochemistry at Boston Medical Center. After graduating from medical school at the University of New Mexico School of Medicine, he had two fellowships: one in Surgical Pathology at Harvard Medical School and another in Hematopathology at Johns Hopkins Medical Institution. He joined the faculty at Boston University in 2018 where he brought extensive experience as a lecturer, mentor, and physician with a particular interest in lung cancer pathology. In his role as Medical Director for Hematopathology and Immunohistochemistry Eric has established a repository of well-annotated lung cancer samples that will be immune profiled as part of these studies to support additional funding opportunities for ongoing studies to establish biomarkers to better detect aggressive lung cancers.
Identifying Coding and Non-Coding Genomic Alterations Associated with Aggressive Prostate Cancer in African American Men
In collaboration with Drs. Joshua Campbell and Rachel Flynn, the overall goal of this pilot project is to identify coding and non-coding genomic alterations in the racially and socioeconomically diverse patient population surgically treated for prostate cancer at Boston Medical Cancer. In particular, we aim to identify a genomic signature associated with more aggressive disease in African American men, as well as establishing a pipeline to integrate these genomic data with other biomarker measurements (e.g. presence of ctDNA, microbiome signatures) and clinical outcomes in a larger cohort of men to create a comprehensive snapshot of these patients at the time of diagnosis and subsequently following treatment.
Meet the Team
Dr. Christopher Heaphy is a member of the Boston University-Boston Medical Center Cancer Center and is an Assistant Professor of Medicine and Pathology & Laboratory Medicine. His research program uses a combination of tissue-based, cell-based, and molecular approaches to study genomic alterations as it relates to cancer initiation and progression across a wide range of cancer types. In addition, his laboratory focuses on how the detection of these alterations may be readily translated into accurately predicting cancer risk, early detection, prognosis, and potential response to targeted therapies.
Dr. Joshua D. Campbell received his Ph.D. in Bioinformatics from Boston University. He performed his postdoctoral research at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT where he worked with The Cancer Genome Atlas (TCGA) to identify novel mutational drivers of lung cancer. He is currently an assistant professor in the Department of Medicine at Boston University School of Medicine where he utilizes genomic data to uncover biological mechanisms that may contribute to cancer disparities.
Dr. Rachel Flynn received her Ph.D. in Cancer Biology from the University of Massachusetts Medical School and conducted her Postdoctoral Fellowship in Molecular Oncology at the Massachusetts General Hospital at Harvard Medical School. Dr. Flynn is currently an Associate Professor in the Departments of Pharmacology & Experimental Therapeutics, and Medicine where the focus of her lab is to define the mechanisms regulating mammalian telomere maintenance and to understand how defects in this process contribute to tumorigenesis. She hopes these studies will allow her lab to gain the mechanistic insight necessary to identify novel targets and/or strategies in the treatment of cancer.
Liver-dependent Lung Remodeling and Pneumonia Susceptibility During Sepsis
It has long been known that systemic inflammatory events, such as those inherent to sepsis, tremendously predispose patients to hospital-acquired lung infections. Yet, the biological pathways influencing lung immunity during sepsis are poorly understood. Dr. Lee Quinton’s research has now established that liver responses to systemic inflammation calibrate the immunological tone of lung tissue, increasing its capacity to respond to subsequent infections. This study will leverage liver-specific mutant mouse models and single-cell sequencing to delineate cell-specific changes within the lung that rely on intact liver function, pursuing the hypothesis that during sepsis, liver activity dictates the transcriptional fingerprint of lung cells, including alveolar macrophages, to limit pneumonia susceptibility.
Dr. Lee Quinton is an Associate Professor of Medicine, Microbiology, and Pathology. He joined the faculty in the Pulmonary Center in 2008 after completing his post-doctoral fellowship at the Harvard School of Public Health. Dr. Quinton’s research program focuses on molecular mechanisms governing immunity and tissue protection during pneumonia. In particular, his laboratory has identified liver activation as a conduit through which early response cytokines promote local and systemic defense in response to lung infections. Additional investigations in Dr. Quinton’s laboratory are focused on deciphering signals controlling epithelial barrier integrity in the pneumonic lung, with the specific goal of determining when, where, and how lung cells collaborate to limit inflammatory injury.
Modeling the Anemia Elicited by Chronic Kidney Disease in Zebrafish
The goal of this research is to uncover how the interplay between microRNAs and uremic solutes orchestrate the responsiveness to erythropoiesis-stimulating agents (ESA) in chronic kidney disease (CKD). To this end, this project will model the anemia of CKD using zebrafish embryos as a model system. Preliminary data suggest a protective role of miR-451 in front of the oxidative stress induced by the uremic milieu. The findings from this project will have the potential to be developed into biomarkers and drug targets to enhance the precision of ESA therapeutics.
At the intersection of uremic toxicity and microRNAs, this proposal is innovative because it probes, for the first time, the effect of a set of uremic solutes on microRNA biogenesis, examines zebrafish as a model of uremic toxicity and the mechanism of ESA-responsiveness in end-stage renal disease patients. The novelty of the proposal is driven by an interdisciplinary team experienced in microRNAs and zebrafish (Dr. Cifuentes), and uremic toxicity (Dr. Chitalia).
Meet the Team
Dr. Daniel Cifuentes is an Assistant Professor in the Department of Biochemistry at the Boston University School of Medicine. Dr. Cifuentes received his Ph.D. from the University of Barcelona, Spain, for his studies in metabolic regulation. He completed his postdoctoral training in the Department of Genetics at Yale University School of Medicine, where he specialized in microRNA biology and vertebrate embryogenesis. His research goals at Boston University combine high-throughput genetic, genomic, and proteomic approaches to address fundamental questions of RNA regulation in viral and vertebrate systems.
Dr. Vipul Chitalia is an Associate Professor of Medicine at Boston University School of Medicine and an attending nephrologist covering renal consults, dialysis, and kidney transplant in-patient services as well as an affiliation to Harvard-MIT Division of Science and Technology, MIT. Teaching is his passion and he considers it an honor to be able to contribute to the training of the next generation of physicians, scientists, and physician-scientists. He strongly believes that a true mentor is one who inspires passion from within and empowers a mentee to find his or her own path of success.
Multimodal Microscopic Characterization of Novel Humanized Mouse Models of COVID-19
Improved animal models that faithfully recapitulate histologic phenotypes of severe COVID-19 are needed to enhance our understanding of host and viral determinants affiliated with SARS-CoV-2 pathogenesis. Current animal models fall short in that they either result in mild subclinical disease reflective of most COVID-19 cases or result in fatal neuroinvasion that is not documented in humans. In collaboration with Drs. Florian Douam (Boston University), Alex Ploss (Princeton), and Alejandro Balazs (Ragon Institute), we will microscopically characterize humanized mice engrafted with human lung xenografts in the absence and presence on concurrent human hematopoietic stem cells (dual engrafted). We will utilize a broad array of microscopic techniques including histomorphology, transmission electron microscopy, and multiplexed immunofluorescent immunohistochemistry to systemically characterize the immunopathologic landscape of these humanized mouse models. Because of the ability of our mouse model to integrate a multi-layer functional human immune response, we hypothesize this project will provide unprecedented insights into the cellular and molecular mechanisms that define SARS-CoV-2 immunopathogenesis and severe COVID-19 disease. Importantly, our findings will be integrated with transcriptomics and proteomics datasets to elucidate specific biological pathways driving morphomolecular findings. Through a better understanding of these mechanisms, this work will open significant opportunities for the development of better-targeted therapeutics and immunotherapies against COVID-19.
Dr. Nicholas Crossland is a veterinary pathologist, Assistant Professor in the Department of Pathology, and the director of the NEIDL’s Comparative Pathology Laboratory (NCPL) core. His team provides pathology expertise to NEIDL investigators and their respective laboratories working in BSL-3 and BSL-4. His research interest is in the systematic multimodal microscopic characterization of animal models to better define pathogenic mechanisms of emerging infectious diseases. He also finds fulfillment in utilizing his expertise to evaluate the efficacy of vaccines and therapeutics in preclinical models as a means to prevent and/or alleviate human suffering.
Non-invasive Blood Flow to Predict Recovery from Coma in Brain Injured Patients
We aim to determine the effect of cerebral blood flow on coma recovery, testing the hypothesis that non-invasive cerebral blood flow measurements following acute brain injury can predict recovery. We will use a novel non-invasive monitor to determine CBF, continuously following admission in stroke, traumatic brain injury (TBI), and post-cardiac arrest comatose patients. We will also evaluate the effect of skin color on non-invasive optical blood flow measures, with the understanding that skin color may introduce a correctable bias in cerebral blood flow measurements in awake and comatose brain patients, important to our diverse populations at BU/BMC.
Dr. David Greer is Professor and Chair of the Department of Neurology at Boston University School of Medicine and the Richard B. Slifka Chief of Neurology at Boston Medical Center.
Dr. Greer is the editor-in-chief of Seminars in Neurology, and the immediate past editor-in-chief for Neurocritical Care ON CALL. He has authored more than 250 peer-reviewed manuscripts, reviews, chapters, guidelines, and books.
His research interests include predicting recovery from coma after cardiac arrest, brain death, and multiple stroke-related topics, including acute stroke treatment, temperature modulation, and stroke prevention.
Dr. David Chung is a neurointensivist and translational neuroscientist in the Department of Neurology. He completed his MD/PhD and Neurology residency at Columbia University and a fellowship in Neurocritical Care at Harvard-MGB. Dr. Chung is an expert in cerebral blood flow and is dedicated to finding ways to improve long-term outcomes in patients with acute brain injury.
Dr. David Boas is a professor in Biomedical Engineering. His research areas of interest are: Neurophotonics, Biomedical Optics, Oxygen delivery and consumption, Neuro-vascular coupling, Physiological Modeling
Patient Perspectives on Disrespect and Abuse in Maternity Care
Experiences of disrespect and abuse during childbirth in healthcare facilities have been associated with subsequent PTSD, avoidance of maternal health services, and increased risk of maternal morbidity and mortality. This global human rights issue has largely been reported in low and middle-income countries but is under-investigated in the United States and Europe. Limited data on women’s experiences in the United States indicate meaningful rates of disrespect and abuse, with significant racial and ethnic disparities. Given the disproportionately increasing rates of pregnancy-related mortality and severe morbidity among minoritized racial groups in the United States, it is imperative that we understand the factors and specific behaviors that contribute to these experiences of disrespect and abuse during maternity care. This study will use mixed methods to assess the prevalence and experiences of disrespect and abuse among women delivering at Boston Medical Center (BMC). Our findings will serve as pilot data for a planned March of Dimes grant.
Dr. Tejumola Adegoke is an Assistant Professor of Obstetrics & Gynecology (OBGYN) at Boston University School of Medicine (BUSM) and an attending physician in the Department of OBGYN at Boston Medical Center (BMC). She is a clinician-investigator who provides full-scope reproductive and gynecologic care at BMC to human immunodeficiency virus (HIV)-infected patients at the BUSM/BMC’s Centers for Infectious Diseases. Her research focuses on eliminating injustice in form of disparate perinatal and gynecologic care experiences and outcomes for Black women. Dr. Adegoke received her undergraduate degree from Princeton University and obtained her medical degree from Rutgers – Robert Wood Johnson Medical School. She also earned her Master of Public Health from the Johns Hopkins Bloomberg School of Public Health and medical degree from Rutgers – Robert Wood Johnson Medical School. Dr. Adegoke completed a residency in Obstetrics and Gynecology at Boston Medical Center and joined the faculty in 2018. She serves as the department Director for Equity & Inclusion and represents the ACOG in Massachusetts’ state commission on racial inequities in maternal health.
Dr. Rachel Cannon is an Assistant Professor in Obstetrics and Gynecology at Boston University School of Medicine and an attending physician in the department of Obstetrics and Gynecology at Boston Medical Center. She provides full-scope OBGYN care and specializes in complex contraception and abortion. Her academic research interests include contraceptive counseling, reproductive justice, and health equity. She co-chairs the Health Equity Committee in the Department of OBGYN.
Dr. Cannon completed an undergraduate degree in Human Physiology at Boston University. She then completed her medical degree at the University of Massachusetts followed by a residency in OBGYN at Northwestern University. She specialized in abortion and complex contraception by completing a fellowship in Family Planning at Boston Medical Center. While in fellowship, she earned a Masters of Science in Health Services Research through Boston University School of Public Health. She advises the Boston University School of Medicine ACOG OBGYN Interest Group. Dr. Cannon serves as Ryan Program Director in the Department of OBGYN residency program and is responsible for the family planning curriculum for OBGYN residents.
Dr. Katharine Hutchinson is an Assistant Professor in Obstetrics and Gynecology at BUSM and an attending midwife at BMC. She is the Co-Director of Advocacy Initiatives for the Department and provides full-scope midwifery care to clients at BMC. Her research interests include Respectful Maternity Care and patient experiences of birth during COVID.
Dr. Hutchinson completed her undergraduate degree at Swarthmore College, followed by her midwifery training at Yale University, and her doctorate at BUSPH. Her dissertation examined access to emergency obstetric care for preeclamptic and eclamptic patients in Port au Prince, Haiti.
Prediction of Knee Pain Using Ultrasound Imaging and Machine Learning
This project (in collaboration with Dr. Juan-Pablo Lopez-Zertuche Ortiz, Dr. Eugene Kissin, and Dr. David Felson) proposes to develop advanced machine learning approaches that can process ultrasound images to predict knee pain.
Meet the Team
Dr. Vijaya Kolachalama is an Assistant Professor within the Department of Medicine, Boston University School of Medicine and the Department of Computer Science, Boston University, and a founding member of the Faculty of Computing & Data Sciences at Boston University. Research in his group is focused on developing advanced machine learning algorithms that have diagnostic relevance. His laboratory is funded by multiple awards from the National Institutes of Health, American Heart Association, private foundations, and the pharmaceutical industry. His course entitled Machine Learning for Biomedical Applications attracts a diverse set of individuals with little to no background in computer science.
I serve as the program director for the rheumatology fellowship program and have a shared focus in medical education and in musculoskeletal ultrasound development. I helped found and lead the training program for USSONAR, the preeminent group for musculoskeletal ultrasound education in North America. I was selected to the American College of Rheumatology (ACR) Core Expert Panel for appropriateness criteria for musculoskeletal ultrasound use in rheumatology as well as the ACR musculoskeletal ultrasound task force and RhMSUS Development Project for musculoskeletal ultrasound certification. In addition, I am responsible for medical student and resident rheumatology rotations at Boston University Medical Center.
Role of ZEB2 in Pericytes Development and Renal Fibrosis
The goal of this pilot grant is to elucidate the role of ZEB2 in kidney fibrosis. ZEB2 is a SMAD-interacting transcriptional factor and is expressed in Foxd1+ stromal cells that are progenitors for pericytes and fibroblasts during kidney development. Pericytes and fibroblasts are the key cell types contributing to the myofibroblasts during kidney fibrosis. We will analyze the histopathological changes in the kidneys of Zeb2 stromal-specific conditional knockout mice (Zeb2flox/flox; Foxd1Cre+) which developed kidney fibrosis. The outcome of this project will help understand the cellular and molecular mechanisms of kidney fibrosis and pericyte/fibroblast development.
Dr. Sudhir Kumar is an assistant professor of medicine in the Nephrology Section, Department of Medicine at Boston University School of Medicine. His research work focuses on Slit-Robo signaling in kidney diseases and podocyte biology and ZEB2 signaling in kidney development and diseases using animal models. Dr. Kumar received his Ph.D. from Ludwig Maximilians University Munich, Germany, and completed his postdoctoral training in Dr. Weining Lu’s lab, Nephrology Section at Boston University School of Medicine.
SARS-CoV-2 Diversity and Transmission Among Healthcare Personnel
Healthcare personnel (HCP) have been disproportionately affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however little is currently known about where and under what conditions SARS-CoV-2 transmission occurs in clinical settings. This study will combine viral whole-genome sequencing with rich epidemiological and contact tracing data on a unique cohort of healthcare workers and nosocomial patient cases spanning the initial COVID-19 surge in Boston. With a team of experts from Boston Medical Center, Boston University School of Public Health, and the Boston University National Emerging Infectious Diseases Laboratory, we aim to uncover how SARS-CoV-2 transmission in the hospital setting was successfully extinguished and identify circumstances where outbreaks persisted. A better understanding of SARS-CoV-2 transmission dynamics among healthcare workers and their patients will provide essential information for limiting hospital transmission in the ongoing pandemic.
Meet the Team
Dr. Tara Bouton is an assistant professor of medicine in the Section of Infectious Disease at Boston University School of Medicine. Her primary research interests are in the clinical and molecular epidemiology and genomics of drug resistance of tuberculosis and the impact of HIV co-infection. However, over the last year, she has served as co-investigator in two COVID-19 clinical trials and helped to develop a large healthcare worker SARS-CoV-2 cohort study using viral whole-genome sequencing to understand nosocomial transmission dynamics. She is currently PI on a prospective effort to bring near real-time sequencing to infection control at BMC.
Dr. John Connor is an Associate Professor of Microbiology at Boston University School of Medicine and an investigator at the National Emerging Infectious Diseases Laboratory. He leads a team of researchers that are studying the virus-host interaction through a variety of strategies including photonics, molecular virology, cell biology, and different omics approaches. These efforts include discreet programs in developing antiviral drugs, light-based diagnostics, and predictive/prognostic biomarker ID to help identify and treat viral disease. These studies have in the past focused on diseases like Ebola, Marburg, and Lassa Fever. During the COVID-19 pandemic, his laboratory has been heavily involved in mapping SARS-CoV-2 transmission through populations by analyzing the virus genome from patient samples and tracking its evolution.
Soft Robotic Technologies Enabling Safe Laparoscopic Bowel Manipulation
Laparoscopy is a minimally invasive technique to perform abdominal surgery through multiple small incisions in the abdomen. While this technique provides considerable advantages to the patient, it introduces several challenges to the surgeon that needs to carry out complex procedures with simple surgical tools, consisting of a long shaft with a distal end effector.
This becomes critical when manipulating delicate anatomical structures and can negatively affect the outcome of a procedure as well as the range of tasks that can be performed. Issues in laparoscopically manipulating delicate organs are caused by: 1) the inadequacy of tools in terms of dexterity and lack of compliance; and 2) the inability to sense applied mechanical stress.
This project’s endpoint will be the development of a soft atraumatic tissue manipulator for laparoscopic retraction of the bowel by exploiting soft robotic technologies. Safe and effective endoluminal tissue manipulation will be guaranteed by the design and constituent materials used for the construction of the manipulator, and through integrated pressure sensing elements that will monitor the interaction with tissues.
The proposed work will be carried out in collaboration with Donald Hess, MD, (Co-PI) Assistant Professor of Surgery, Boston University School of Medicine, Chief, Section of Bariatric Surgery, and Director of the Bariatric Surgery Program.
Dr. Tommaso Ranzani is an Assistant Professor in the Department of Mechanical Engineering, Biomedical Engineering, and in the Division of Materials Science and Engineering at Boston University. He received a Bachelor’s and Master’s degree in Biomedical Engineering from the University of Pisa, Italy. He did his Ph.D. at the BioRobotics Institute of the Sant’Anna School of Advanced Studies, and he joined the Wyss Institute for Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences as a postdoctoral fellow in 2014.
At Boston University, he founded the Morphable Biorobotics Lab. The lab focuses on expanding the potential of soft robots across different scales to develop novel reconfigurable soft-bodied systems with applications ranging from environmental exploration to assistive and soft surgical robots.
Dr. Donald T. Hess is a graduate of Williams College in Williamstown, MA, and received his medical degree from the University of Rochester School of Medicine and Dentistry in Rochester, NY. He completed a residency in general surgery at Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA, and a research fellowship in Surgical Oncology at New England Deaconess Hospital in Boston, MA. He started at Boston University Medical Center after working for the US Air Force as an Assistant Professor of Surgery stationed at Wright-Patterson Air Force Base (WPAFB) in Ohio.
His clinical practice is devoted to minimally invasive and bariatric surgery. He has tremendous surgical expertise in laparoscopic bariatric surgery (sleeve gastrectomy and gastric bypass) and revisional bariatric surgery. He also has an interest in minimally invasive surgery, robotic surgery, surgery for disease of the stomach and esophagus, intestinal surgery, single-site surgery, complex hernia surgery, and general surgery. He is also the program director of the General Surgery residency and is heavily involved in surgical education.
Dr. Hess is involved in many research protocols involving metabolic and cardiovascular disease in patients undergoing bariatric surgery. He is a member of the Association of Metabolic and Bariatric Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, a fellow of the American College of Surgeons (ACS). He has been recognized by Boston Magazine’s “Top Docs” issue for being “top” in his respective field since 2009 and was a 2013 recipient of the Boston University School of Medicine Evans Center Collaborator of the Year Award.
Validating the Role of Extracellular Matrix Molecules in Parkinson’s Disease Using Mass Spectrometry Glycomics and Proteomics
Brain extracellular matrix (ECM) consists of hyaluronan, glycosaminoglycans (GAGs), proteoglycans (PGs), glycoproteins, and a variety of post-translational remodeling proteases. GAGs and PGs play intricate roles in neuronal processes, including axonal growth/degeneration, synaptic plasticity, and neurite outgrowth in neurodegenerative disorders, including schizophrenia, Alzheimer’s disease, and Parkinson’s disease (PD). Importantly, ECM networks modulate axonal growth/degeneration and synaptic dysfunction that contribute to PD. Thus, ECM abnormalities may denominate the dysregulation of these processes in PD. However, despite the apparent importance of the ECM molecules to neurodegeneration, little information is available on the levels and structural alterations of these molecules in ECM of PD brains. A relatively low number of mass spectrometry-based proteomics and glycomics studies have been reported for PD. Thus, this modality for identifying PD-associated targets and pathways remains under-explored for understanding underlying PD pathophysiology.
We assessed the structural alterations of GAGs and proteins in the human PD brain prefrontal cortex relative to controls in two separate cohorts using ultra-high-performance mass spectrometry proteomics and glycomics technology. We identified alterations to GAG structure and enrichment of ECM constituents in the PD brain. This is the most extensive glycomics and proteomics study on PD to date. For any cohort-based study, the only way to eliminate all possible sources of bias related to tissue procurement and processing is to repeat the work using separate biospecimen cohorts in future studies. Thus, we will validate these findings using two new cohorts similar to our previous work, consisting of 12×12 PD and age-matched non-neurological disease controls, instead of one large validation cohort, because of various challenges associated with increasing sample size, including degrading quantitative quality, snowballing missing data and false‐positive discovery of altered proteins. For this study, we will refine our data quality control and acquisition to enhance our ability to assess the findings of our previous study. Our unbiased and nuanced view of alterations of ECM glycans, proteins, and genes will solidify our knowledge of PD pathology and uncover targets for more effective and preventive therapeutic strategies.
We will conduct this work at the BU Center for Biomedical Mass Spectrometry, where Dr. Sethi (PI of the project) works as an Instructor. The biospecimens will be provided by Dr. Thor D. Stein, a neuropathologist at the BU-VA-CLF Brain bank, who will serve as a Co-PI on the project.
Dr. Manveen K. Sethi serves as Instructor of Biochemistry at the Boston University School of Medicine, USA. She did her Ph.D. at Macquarie University (MQ), Australia, under the primary supervision of Dr. Morten Thaysen-Andersen, where she utilized mass spectrometry proteomics and glycomics analysis to understand underlying molecular mechanisms in colorectal cancer. After her Ph.D., she joined Boston University School of Medicine (BUSM), USA, as a postdoctoral associate under Prof. Joseph Zaia, where she is currently employed in a research faculty-track position of Instructor. Her research work involves identifying and characterizing biomolecules such as proteins and glycans using mass spectrometry techniques and utilizing this information to understand biomolecular deregulation in human diseases, such as cancer and Alzheimer’s disease. Recently, she received a Bright Focus Foundation fellowship award to investigate extracellular matrix changes in Alzheimer’s disease.
Dr. Thor Stein is Associate Professor of Pathology and Laboratory Medicine and Associate Director of the Neuropathology Core of the BU Alzheimer’s Disease Center as well as staff neuropathologist at the VA Boston Healthcare System (VABHS). Dr. Stein’s research interests involve the study of neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). He studies the role of trauma in the development and acceleration of multiple types of neurodegenerative disease. He has published extensively on the development and modeling of age- and trauma-related neuropathologies, including the most comprehensive studies to date on beta-amyloid deposition, cerebral amyloid angiopathy, and Lewy body disease following repetitive mild traumatic brain injury. Dr. Stein is the Principle Investigator on numerous grants, including a VA Merit Award on the role of traumatic brain injury in the development of AD and CTE as well as multiple NIH R01s, focused on determining the link between epigenetic modifications, lipidomic profiles, and pathological changes in the brain as they relate to cognitive decline.
2020 Integrated Pilot Grant Awardees
Peer Recovery Coaching for HCV and Opioid Use Disorder Treatment
The U.S. opioid epidemic is associated with a surge in hepatitis C virus (HCV) infections among persons who inject drugs. Despite the availability of curative therapy, treatment uptake remains low in this group. The goal of this study is to determine the feasibility and acceptability of a peer intervention to improve linkage to HCV care, treatment initiation, and cure among individuals with a history of opioid use disorder. Our findings will serve as pilot data for a planned NIH R01 proposal.
Sabrina A. Assoumou, MD, MPH, is Assistant Professor of Medicine at Boston University School of Medicine and an attending physician in the section of Infectious Diseases at Boston Medical Center. She is a clinician-investigator who provides care to human immunodeficiency virus (HIV)-infected patients at the BUSM/BMC’s Centers for Infectious Diseases. Her research focuses on medical complications of substance use including HIV and hepatitis C virus (HCV). She is also interested in models of care and improving the continuum of care for individuals with HIV/ HCV. She is currently the Principal Investigator on a NIH K23 Mentored Career Development Award to improve linkage to care after testing for HIV and HCV at a drug detoxification center.
Dr. Assoumou graduated magna cum laude from Williams College and obtained her medical degree from the University of Rochester School of Medicine and Dentistry. She then completed a combined Internal Medicine-Pediatrics residency at Brown University and an Infectious Diseases Fellowship at Harvard University’s Beth Israel Deaconess Medical Center where she was awarded the Finland Award for Research Excellence. She also earned a Master of Public Health at the Harvard T.H. Chan School of Public Health. Dr. Assoumou received an Excellence in Teaching Hospital-Based Faculty Award at BMC in 2017. She was also recognized as the Distinguished Faculty of the Month in April 2020 for her service to the BUSM community in teaching, activities on committees, and the mentoring of students, trainees, and junior faculty.
Data-Driven Youth-Led Health Promotion Strategy for a Safety Net Accountable Care Organization
The “Data-Driven Youth-Led Health Promotion Strategy for a Safety Net Accountable Care Organization” is a partnership between researchers at the Boston University School of Social Work and Boston Medical Center’s Department of Family Medicine. The overall goal of the project is to develop and vet a youth-driven health promotion campaign informed by a youth-led health assessment. The research will be guided by a youth advisory board consisting of six to eight youth of color who will be trained in the principles of youth participatory action research (YPAR), health equity, the social determinants of health, health promotion practice, and data-driven planning.
Astraea Augsberger is an Assistant Professor at Boston University School of Social Work. She earned her MSW and Ph.D. from Columbia University. She has over a decade of clinical practice experience with children, youth, and families in the child welfare, juvenile justice and mental health systems. Her research interests include youth civic engagement, youth development, child welfare policy and programs, and health equity. She employs community-engaged research, youth participatory action research, and in-depth qualitative research methods to elevate the voices of youth and communities in identifying research priorities and relevant solutions to community concerns. She is an affiliated faculty member of the Boston University Center for Innovation in Social Work & Health (CISWH) and the Boston University Initiative on Cities (IOC).
Dr. Katherine Gergen Barnett is the Vice-Chair of Primary Care Innovation & Transformation and the Program Director in the Department of Family Medicine at Boston Medical Center (BMC). Katherine joined BMC in 2009 after completing her residency and chief residency there. Prior to BMC, Dr. Gergen Barnett attended Yale University School of Medicine, worked at NIH, and completed a fellowship studying a model of group prenatal care for underserved women.
Dr. Gergen Barnett’s primary interests are behavioral health integration, preventive medicine, nutrition, mindfulness-based stress reduction, women’s health, and group care. Dr. Gergen Barnett’s research career has been primarily focused on innovative models of care to address chronic medical conditions, physician burnout, and engaging community partners in creating feasible solutions to increase health and wellness in urban communities.
“Immune Response and mEdical Complications of coVid-19 suRvivors (I-RECOVR) study”
The Study will follow a cohort of recovered patients to evaluate if those who survive acute illness with COVID-19 are at risk for continued physical disabilities or new medical sequalae, and whether these presentations are determined by initial disease severity or patient characteristics. Additionally, the study will follow this cohort over a two-year period of time to determine if survivors of COVID-19 are at risk for reinfection with SARS-CoV-2 and evaluate if incidence of reinfection or medical sequelae after recovery are associated with nature and longevity of immune response. Dr. Bhadelia serves as the principal investigator of a prospective biorepository study supported by a grant from Massachusetts Coalition for Pathogen Readiness and through internal support from Boston Medical Center. Currently, the study, entitled “Natural History of COVID-19 Confirmed Cases at Boston Medical Center (IRB H40047),” includes the longitudinal follow up of 200 hospitalized COVID-19 patients. This study is in the process of being expanded to cover 100 ambulatory COVID-19 patients and the two- year follow up of 200 COVID-19 survivors. The prospective study collects basic demographic and medical information as well as biological samples for use by Boston Medical Center and Boston University researchers. I-RECOVER study is layered on top of the survivor arm of this study and this pilot grant will be used to conduct survey tools, in person interviews, and collect biological samples for analysis mentioned above. The pilot data generated from the early part of I-RECOVER project will be used to support an R01 grant that will fund virologic and immunologic analysis on the stored samples as well as more extensive imaging of survivors with continued medical sequelae.
Dr. Nahid Bhadelia is an infectious diseases physician and the Medical Director of Special Pathogens Unit at Boston University School of Medicine, a medical unit designed to care for patients with highly communicable diseases. She is an Associate Professor in the Section of Infectious Diseases. She oversees the medical response program for Boston University’s maximum containment Biosafety Level 4 program at National Emerging Infectious Diseases Laboratories.
During the West African Ebola epidemic, she served as a clinician in several Ebola treatment units, working with World Health Organization and Partners in Health. She currently serves as the clinical lead for the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC) program which is a joint US-Ugandan effort to create clinical research capacity to combat viral hemorrhagic fevers in Uganda at the border of Democratic Republic of Congo. She serves on national and interagency groups focused on medical countermeasures, the intersection between public health preparedness, research, and clinical care for emerging pathogens. Her research focuses on identification of safe and effective clinical interventions and infection control measures related to viral hemorrhagic fevers.
She has served as a subject matter expert to US Centers for Disease Control and Prevention, Department of Defense, Global Fund to Fight AIDS, Tuberculosis and Malaria, and World Bank.
Dr. Bhadelia is also an Assistant Professor at the Institute of Human Security at the Tufts Fletcher School of Law and Diplomacy, where she teaches a course on human security and emerging infectious diseases. She received her Doctorate of Medicine from Tufts University and completed her internal medicine residency and chief residency at Mount Sinai Hospital in New York. Her Infectious Diseases Fellowship was completed at Columbia Presbyterian Hospital.
PTH/PTHrP Receptor Signaling in Osteocytes during Aging
Dr. Divieti Pajevic’s research is focused on studying the effects of hormones, such as parathyroid hormone, and mechanical forces on bone and teeth. Recently, her group has been investigating the cross-talk between bone and muscle and the effects of aging. In her current CTSI proposal titled “PTH/PTHrP Receptor Signaling in Osteocytes During Aging,” Dr. Divieti Pajevic will use a combination of genetically modified mice and cell lines to investigate if PTH signaling in osteocytes alters skeletal progenitors and protects these cells from senescence.
Paola Divieti Pajevic, MD, PhD, is an Associate Professor of Translational Dental Medicine at the Goldman School of Dental Medicine at Boston University and the Director of the Bone Cells Core which is part of the MGH-Center for Skeletal Research.
Lionoleic Acid Promotes Pathogenic T Cells in Type 1 Diabetes
Type 1 Diabetes is an autoimmune disease caused by T cells that destroy the insulin-producing beta-cells in the pancreas. The incidence of Type 1 Diabetes is rapidly rising worldwide due to currently unknown environmental factors that promote the autoimmune response in genetically susceptible individuals. There is growing evidence that specific metabolites derived from the diet or microbiome have the capacity to influence the functions of T cells and may promote pathogenic T cells in autoimmune diseases. We discovered that addition of the dietary fatty acid linoleic acid to in vitro T cell cultures altered the balance between pathogenic IL-21-producing and protective IL-10-producing T cell subsets in favor of the cells with pro-diabetic activities. The goals of this CTSI pilot grant are to test whether autoreactive T cells exposed to linoleic acid have an increased capacity to cause diabetes in vivo, and whether feeding diabetes-susceptible NOD mice a linoleic acid-rich diet will accelerate diabetes development. Our study has the potential to identify a dietary factor that is increasingly present in Western diets as a driver for increased Type 1 Diabetes susceptibility. This finding may form the basis to develop preventative dietary interventions in susceptible individuals and/or to target the metabolic and signaling pathways that underlie linoleic acid-based induction of diabetes-causing T cells.
Dr. Hans Dooms is an immunologist who currently holds a position as an Assistant Professor in Medicine and Microbiology at the Arthritis and Autoimmune Diseases Research Center of Boston University School of Medicine. He received his Ph.D. from Ghent University in Belgium and continued his training in immunology at the University of California San Francisco in the laboratory of Dr. Abul Abbas. His research interests are focused on the biology of T cells and their role in the autoimmune diseases Type 1 Diabetes and Systemic Sclerosis. His laboratory is currently studying how autoreactive T cells acquire and maintain their disease-causing properties and how these cells escape immune regulatory mechanisms aimed at preventing autoimmunity. Dr. Dooms has received funding for his research from NIH, JDRF, and the American Diabetes Association. He has authored 29 publications, many included in some of the most prestigious journals in the field of immunology.
Defining the Role of Hippo Pathway Inactivation in Melanomagenesis
Dr. Ganem’s CTSI award is focused on testing the hypothesis that inactivation of the Hippo tumor suppressor pathway plays an important role in melanoma development.
Neil J. Ganem is an Associate Professor in the Department of Pharmacology & Experimental Therapeutics, and Department of Medicine, Division of Hematology and Oncology. He directs the Laboratory of Cancer Cell Biology, where his team used a combination of high-resolution microscopy, genome-wide screening, bioinformatics, and animal model systems to understand the causes and consequences of genome instability in human cancer.
Primary Care Connection in Maine
Millions of Americans have gained health insurance under the Affordable Care Act’s Medicaid expansion. However, health insurance is only a first step toward the goal of improving population health; receipt of primary care is a critical follow-up step. Despite the array of known benefits of primary care, little empirical work has examined how states can encourage uptake of primary care among new Medicaid enrollees. To address this gap in the evidence, we propose to design and pilot test an intervention to increase engagement with primary care services among newly enrolled Medicaid beneficiaries in the state of Maine, in partnership with the Office of Member Services (OMS) at the Maine Department of Health and Human Services. The pilot study will be a single blinded, randomized, controlled trial of a behavioral intervention to increase the PCP visit rate within the first six months of new Medicaid enrollment. The treatment arm will receive a one to two page letter that encourages new enrollees to get a free checkup and recommends a single provider, located within 30 miles of the enrollee’s home address. Clinics will be notified of newly assigned patients and encouraged to reach out to schedule initial appointments. The control arm will receive the current MaineCare enrollee packet of 23-pages, including a comprehensive provider directory. We will assess acceptability and feasibility of our intervention to MaineCare members, providers, and our partners at OMS. If the pilot trial proves acceptable and feasible, we will plan to implement a larger scale trial within 6 months of the pilot’s end.
The research team for this project includes Anna Goldman, MD, MPA, MPH, of BUSM/BMC; Sarah Gordon, PhD, MPH, of BUSPH; and Benjamin Sommers, MD, PhD, of Harvard T.H. Chan School of Public Health.
Anna L. Goldman MD, MPA, MPH, is a general internist practicing primary care, and a health services researcher. Her research centers on the effects of insurance and payment policies on care access for the poor and undeserved. She focuses on the health insurance programs established by the Affordable Care Act, the Medicaid expansion and Marketplace insurance. She also investigates the effects of accountable care organizations (ACOs) in the Medicaid program on health care quality and access. She has a medical degree from Mount Sinai School of Medicine, a Master’s Degree in Public Health from the Harvard T.H. Chan School of Public Health,and a Master’s Degree in Public Affairs from Brown University. She completed an internal medicine residency at Cambridge Health Alliance.
Sarah Gordon is an Assistant Professor in the Department of Health Law, Policy, and Management at the Boston University School of Public Health. Her research is dedicated to studying coverage and access to care among low-income populations, with a particular emphasis on Medicaid policy. Her work seeks to understand how the fragmentation of the U.S. health insurance system impacts utilization, quality, and continuity of care. Dr. Gordon recent projects leverage state-level datasets, such as all payer claims databases, and quasi-experimental study designs to evaluate the effects of state-level policies. She received her doctorate in Health Services Research from the Brown University School of Public Health and a M.S. in Social and Behavioral Sciences from the Harvard T. H. Chan School of Public Health
A Tool to Identify PrEP Eligible Youth in Primary Care
Pediatricians are the most common provider of primary care for youth, and frequently provide care to individuals through their early-to-mid 20s. Thus, pediatric primary care offers an opportune setting for identifying youth who are eligible for pre-exposure prophylaxis (PrEP). To successfully identify PrEP-eligible youth, it is essential that pediatricians ask valid, developmentally appropriate screening questions that resonate with youth and elicit accurate information. The objective of this proposal is to conduct mixed methods, translational research to develop (Aim 1), and conduct a pilot study (Aim 2) of a HIV risk assessment tool that pediatricians can integrate into their current primary care practice to identify PrEP-eligible youth. Data from the pilot study will directly inform a subsequent clinical trial of a comprehensive PrEP service delivery model for pediatric primary care.
Scott Hadland is a pediatrician and addiction specialist at Boston Medical Center and Boston University School of Medicine. He holds triple board certification in General Pediatrics, Adolescent Medicine, and Addiction Medicine. Dr. Hadland’s clinical and research interests focus on adolescent and young adult substance use disorder prevention and treatment. In the proposed work, Dr. Hadland will extend his work into human immunodeficiency virus (HIV) prevention among youth, with a goal of enhancing pre-exposure prophylaxis (PrEP) delivery in pediatric primary care.
Influenza Induced Lymphangiogenesis
The overall objective of this proposal is to identify lymphatic-centered strategies to contain viral lung infections. To achieve this goal, the PIs use a mouse influenza model that allows for deciphering the functional therapeutic properties and origins of the markedly expanded pulmonary lymphatic system that the PIs found accompanies influenza. Based on preliminary data, the central hypothesis is that new lymphatic growth facilitates immunomodulatory events and alterations in lymphatic cell function that are central to virus containment. The PIs propose to use the CTSI pilot grant to perform a detailed transcriptional analysis of lymphatic cells as the lung responds to influenza.
The PIs driving this project are Dr. Matthew Jones and Dr. Alan Fine. Together, they have a successful history of collaboration on various projects, grants, and papers.
Dr. Matthew Jones is a lung molecular biologist with an extensive history of studying the lung’s response to infection. Dr. Jones also brings a deep knowledge of gene expression analytical methodology to this project.
Dr. Alan Fine is a practicing pulmonologist with broad experience in the treatment of lung disease. He has a long history of external funding that supports work aimed at understanding the fundamental biology of lung cells, lung development, and disease mechanisms.
Clinical Pipeline for Single Cell Profiling of Triple Negative Breast Cancer
The research for this CTSI pilot award will recruit, consent, and invite BMC patients with breast cancer to participate in translational research, by providing biopsy specimens for single-cell RNA sequencing to answer cutting-edge research questions on the behavior of tumor cells and the immune environment.
Dr. Naomi Ko is an Assistant Professor of Medicine at Boston University School of Medicine (BUSM) and a medical oncologist at Boston Medical Center (BMC). Her research is directed to understanding the root causes of cancer disparities, the disconnect between scientific discoveries in cancer treatment, and delivery of evidence-based treatment to vulnerable, racial/ethnic minority women with breast cancer. She is actively investigating how tumor biology, social, and treatment factors influence breast cancer outcomes in undeserved, diverse breast cancer populations.
Single-Cell Analysis of AL Amyloidosis Plasma Cells
Since starting at BUSM in 2018, Gareth has established a program to study the aberrant plasma cells that underlie AL amyloidosis, which is a rare but often fatal form of systemic amyloidosis. These plasma cells normally secrete antibodies as part of the adaptive immune system. Aberrant proliferation in bone marrow causes overproduction of antibodies and, in some cases, amyloidosis. Comparing the gene expression of these cells to that of healthy plasma cells and those from a related disease, multiple myeloma, should reveal specific vulnerabilities that can be targeted for therapy. The CTSI pilot grant will enable researchers from the Amyloidosis Center to measure single-cell gene expression profiles of primary cells isolated from patient bone marrow aspirates. This project brings together the clinical work of the BU Amyloidosis Center with the cutting-edge instrumentation in the Department of Medicine Single Cell Sequencing Core Facility. These experiments will enable larger-scale studies to identify therapeutic targets and prognostic markers that could help to optimize treatments and benefit patients.
Gareth Morgan is a Research Assistant Professor in the Section of Hematology and Medical Oncology at the Boston University School of Medicine, and a member of the BU Amyloidosis Center. Originally from the United Kingdom, Gareth completed his B.Sc. in Biochemistry from Imperial College, London. He received his Ph.D. from the University of Sheffield, where he worked with Professors Rosie Staniforth and Jon Waltho. Gareth worked as a postdoctoral research associate with Professor Sheena Radford at the University of Leeds, and then with Professor Jeff Kelly at the Scripps Research Institute in San Diego, CA. Throughout his career, Gareth has studied how proteins fold, misfold and aggregate. He is especially interested in understanding how cells and organisms manage and maintain their proteomes, and why these processes break down to cause systemic amyloidosis diseases, where accumulation of protein aggregates leads to progressive organ failure. A major research focus is on developing small molecule drugs that can prevent protein aggregation, which could benefit patients with these diseases.
Machine Learning Risk Stratification of Stroke in Patients with AF
We aim to develop a clinically-oriented risk prediction model of stroke in patients with non-valvular atrial fibrillation using novel, clinically-oriented machine learning methods and data from Boston Medical Center and the UK Biobank
Non-valvular atrial fibrillation (NVAF) is associated with a five-fold increased risk of stroke.1 The most widely used prediction scales to risk stratify patients include the CHADS22,CHA2DS2-VASc3, and Framingham Risk scales.1,4 These are commonly used to guide management decisions (anticoagulation or antiplatelet therapy) for primary or secondary stroke prevention. However, like many risk prediction scales, they assume that the addition of risk factors is cumulative and linear,5 which limits their discrimination (C statistics of 0.68-0.7 in large validated studies)6,7 and generalizability. Advances in machine learning (ML) methods allow us to model non-linear risk in large datasets, improving performance, making individualized risk stratification possible. Moreover, our group has developed a novel and interpretable tree-based ML method specifically tailored for clinical applications. Optimal classification trees (OCTs) is an ML method that improves accurate classification compared to traditional statistical methods, while allowing practitioners to easily identify risk factors that contribute to outcomes.8 Such interpretability resolves the “black-box” or opaque classification disadvantage intrinsic to using many ML techniques. Our group has used these methods to stratify patients at high risk for emergent surgery, to predict 10-year cardiovascular risk, and to make treatment recommendations in diabetic patients.5,9,10 ML methods have not yet been used to develop clinically-oriented risk prediction models in cerebrovascular diseases like stroke risk in patients with atrial fibrillation (AF). We propose an innovative approach using a variety of novel, OCT-based methods to improve personalized stroke risk stratification in patients with non-valvular AF. Improved risk stratification would profoundly impact the population’s cardiovascular health, as it can inform management for approximately 5.3 million Americans with AF.11
Charlene Ong, MD, MPHS, is an Assistant Professor of Neurology and Neurosurgery at Boston University, Visiting Assistant Professor at Harvard Medical School and Massachusetts Institute of Technology, and a clinical Neurointensive Care Physician at Boston Medical Center. She received her undergraduate degree at University of Pennsylvania, her MD at Columbia University and her Master’s in Population Health Sciences at Washington University School of Medicine. Her research focuses on data-driven tools that support clinical decision making and optimize outcome after acute brain injury. She has received foundational support from the American Brain Foundation, Philips-MIT, the Peter Paul Career Development Committee, and the Clinical and Translational Science Institute at Boston University. Her aim is to build a robust ICU data science program and follow a K-track path toward the eventual goal of becoming an independently funded researcher and recognized leader in the field of neurocritical care.
Soft Robotic Platform for Restoring Haptic Feedback in Robotic Surgery
Robotic surgery has improved minimally invasive surgical procedures and shortened learning curves for surgeons. However, during robot-assisted procedures, haptic feedback is not available to the surgeon, resulting in uncontrolled force application which can lead to intraoperative complications. Absent haptic feedback is reputed to be among the reasons that impede further spread of surgical robots.
The capability to sense and touch the anatomy realistically has the potential to increase safety and precision during robotic surgery, with better patient outcomes. In this proposal, we will focus on restoring haptic feedback in minimally invasive robotic surgery by developing a soft robotic platform consisting of a soft sensing unit, to monitor forces exerted during surgical tasks and transduce this information to a soft actuation unit, that will map tactile information back to the surgeon.
Sheila Russo is an Assistant Professor in the Department of Mechanical Engineering and the Division of Materials Science and Engineering at Boston University. Prof. Russo completed her Ph.D. degree at the BioRobotics Institute, Sant’Anna School of Advanced Studies, Italy. She completed her postdoctoral training at the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. She is the founder and director of the Material Robotics Laboratory at BU that aims at bridging the gap between material science and robotics, and focuses on design, mechanics, and manufacturing of novel multi-scale and multi-material biomedical robotic systems. Her research interests include medical and surgical robotics, soft robotics, sensing and actuation, meso- and micro-scale manufacturing techniques, and advanced materials.
Pre-Clinical Validation of Novel Gene Editing Approaches for Sickle Cell Disease
With the support of the CTSI pilot grant, Dr. Vanuytsel will further develop the sickle cell disease (SCD)-specific iPSC platform as a pre-clinical tool to validate the efficacy of novel therapeutic gene editing strategies across a diverse SCD patient population.
Although SCD patients all share the same point mutation in the beta globin gene, the surrounding genetic background determines the severity of their disease course and response to therapy. Currently, several gene editing strategies are being explored as potentially curative approaches in clinical and pre-clinical trials. While these developments are truly exciting, their safety and efficacy will require thorough validation across a variety of SCD backgrounds to make sure that an effective treatment can be assured for every patient. iPSCs present an unlimited source of material that can be differentiated into erythroblasts that capture the exact genetic background of a patient, and thus make an excellent screening tool that could help predict the safety and efficacy of a particular therapeutic approach in a given genetic background prior to engaging in costly and invasive treatments.
Kim Vanuytsel is a Research Assistant Professor in the Division of Hematology and Medical Oncology at Boston University School of Medicine and the Center for Regenerative Medicine (CReM). She obtained a PhD in Stem Cell and Molecular Medicine from the Katholieke Universiteit Leuven (KULeuven) in Belgium. As a postdoc in Dr. George J Murphy’s lab, she developed novel resources and tools to better understand and treat blood disorders. Her current research focuses on finding better solutions for sickle cell disease (SCD) patients by using patient-specific induced pluripotent stem cells (iPSCs) as a versatile platform to study the disease, screen for compounds that can ameliorate the condition, and explore potential curative gene editing approaches.