Boston University Clinical and Translational Science Institute (BU-CTSI) is pleased to announce the recipients of the Spring 2018 Integrated Pilot Grant Program. The awards were funded by the CTSI along with two additional sources:
8 were funded by the Department of Medicine
2 were co-funded by the Cancer Center and the CTSI
13 were funded entirely by the CTSI
Louis Awad, PT, PhD & David Boas, PhD
Brain-machine Interface for the Individualized Prescription of Assistance from Soft Robots
The project aims to use non-invasive brain imaging to “peak into the brain” of users with poststroke hemiparesis while they are walking with a garment-like, soft exosuit designed to help them move their legs. We hope to use this information to guide the prescription of the robotic assistance provided to individual users to maximize the orthotic or therapeutic effects of continuous use of the robot for gait assistance.
Sarah Bagley, MD, MSC & Tae Woo Park, MD, MSC
Stigma Associated with Medication Treatment for Youth with Opioid Use Disorder
The funded project is a mixed methods study to examine the role of stigma related to medication treatment for opioid use disorder among young adults.
Deepa Gopal, MD, MSC & Wilson Colucci, MD
Cardiac Phenotyping in Metabolic Heart Disease
The overall objective of the pilot award is to identify a candidate serum biomarker that can predict early, preclinical heart failure by using a precision proteomic platform in both human and mouse models of obesity with early cardiac phenotypic features of HFpEF to eventually help direct HF preventative strategies.
Ulla Hansen, AB, PhD & Andrew Emili, PhD
LSF-partner Protein Interactions Involved in Mitotic Progression
LSF is an oncogenic transcription factor that is required for tumor cells to appropriately progress through mitosis, resulting in cell division. Unexpectedly, this requirement for LSF does not involve transcriptional control, but rather interaction with partner proteins; we will identify key mitotic regulators that specifically bind LSF to uncover this novel mechanism.
Louis Gerstenfeld, PhD & Paul Tornetta, MD
Assessment of Efficacy of Serum Based Indices of Fracture Healing
This pilot project will build on our animal studies that identified 850 serum proteins that change over the time course of fracture healing. We will begin to translate these findings by validating human markers during humerus fracture healing to our preclinical studies, providing us with the human data to allow us to competitively develop a clinical trial for markers for normal and failed fracture healing.
Thomas Kepler, PhD & Andrew Emili, PhD
Establishment of a Serum Antibody Proteomic Sequencing Platform
Drs. Kepler and Emili are joining their respective expertise in B cell dynamics and proteomics to enable the direct study of antibody interactions in human blood. The methods they are developing will overcome the major shortcomings of the indirect methods that are currently in use and provide unprecedented insight into key mechanisms of immunity.
Lawrence Ziegler, DNS & Lee Wetzler, MD
Rapid Antibiotic Susceptibility Testing by Surface Enhanced Raman Spectroscopy
This award will fund our initial efforts to develop an optically based methodology for rapidly determining bacterial antibiotic drug susceptibilities without the need for any cell culture growth Drug resistant and susceptible bacteria offer very different metabolic responses which can be determined in as short as 10 min following antibiotic dosing via nanoparticle enhanced, laser light scattering and portable, relatively low cost instrumentation.
Wilson Wong, PhD & Emili Andrew, PhD
Global Phosphoproteomic Profiling of CAR Activation in Human Primary T cells
The goal of this project is to leverage Dr. Emili’s and Dr. Wong’s expertise in proteomics and cellular immunotherapy to study the signaling dynamics of immune cells activation against cancer cells.
Stephen Pelton, MD & Richard Goldstein, PhD
Serotype Independent Protection against Pneumococcal Disease
We have used a new strategy to identify highly conserved, surface exposed, vaccine candidates for protection against the major bacterial cause of pneumonia and meningitis in children and adults. The CTSI project will evaluate proof of concept that immunization with these promising ‘cold-spot’ protein elicits protection against pneumococcal disease using an experimental chinchilla model.
Kei Yasuda, MS, PhD & Ramon Bonegio, MD
The Effect of Fc Receptor Polymorphisms in the Pathogenesis of SLE
The goal of this proposal is to understand the mechanisms whereby the risk variant of Fc gamma receptor IIA is involved in immune cell activation and SLE pathogenesis. We will use immune cells from peripheral blood of lupus patients and healthy subjects, and stimulate them with sera from lupus patients which contains autoantibodies.
Huiping Zhang, MS, PhD Vidhya Kumaresan, MS, PhD
Cocaine Addiction Epigenetics
Dr. Huiping Zhang and his collaborator Dr. Vidhya Kumaresan will investigate cocaine use/withdrawal induced microRNA expression alterations in the brain’s reward circuit using a translational rat model of incubated drug craving. It is expected that cocaine withdrawal responsive microRNAs could be potential biomarkers for CUDs and novel therapeutic targets.
Tamar Barlam, MD, MSC
FMT after Treatment for Clostridium Difficile
Fecal microbiota transplantation (FMT), now available via capsules without the requirement of an endoscopic procedure, restores the microbiome and has been highly successful in treating recurrent CDI but has had limited study for use after a primary CDI episode. We propose a proof-of-concept study to examine whether FMT administered after oral vancomycin therapy for primary CDI restores microbiome diversity and might be a viable strategy to improve outcomes.
Laurence Beck, MD, PhD
A Novel Complement Fixation Assay for Prognosis in Membranous Nephropathy
The project seeks to answer the question of why there is often a disconnect between the titer of anti-PLA2R autoantibodies in primary membranous nephropathy and the severity and/or outcome of disease? We hypothesize that this may be due to the relative abilities of the subtypes of autoantibody to activate the different pathways of the complement system, and we plan to develop a simple assay to measure levels of complement activation by anti-PLA2R autoantibodies.
Christine Gunn, MA, PhD
Assessing Opportunities for Tailored Risk Communication about Fentanyl Use
Dr. Gunn and her colleagues are using qualitative interviews to explore preferences about fentanyl-related risk communication among persons who have used fentanyl, examining differences by age and gender. The project will also describe the current strategies that community health workers use in talking to people about the high risk of overdose related to fentanyl use.
Zhen Jiang, MD, MSC, PhD
Gut microbiota-myelopoiesis Axis Initiates Obesity-related Systemic Inflammation
The pilot project is designed to evaluate if microbiota changes in the gut in mice fed a diet rich of fat contribute to myelopoiesis in the bone marrow leading to neutrophil production and profile changes as well as subsequent systemic inflammation in obesity.
Jesse Mez, MD, MS
CTE: Cognitive, Neuropsychiatric and MRI Profiles
This study will assess 20 living individuals who have already agreed to brain donation with comprehensive clinical evaluations including clinical history interview, neurological exam, neuropsychological testing, and structural brain MRI. This study will further our ability to diagnose CTE during life and to differentiate it from other related disorders (e.g., Alzheimer’s disease).
Nader Rahimi, MS, PhD
Novel Role of IGPR-1 in Endothelial Barrier Function
The goal of this proposed study is to investigate the role of IGPR-1, a newly identified adhesion molecule, in the vascular leakage associated with sepsis. Sepsis is the second leading cause of death in non-coronary intensive care units, highlighting a significant unmet clinical need.
Christopher Salas-Wright, PhD
Developing an Online AOD Training Program
Health professionals are well positioned to identify and assist individuals experiencing problems with alcohol and other drug (AOD) misuse. Unfortunately, many health professionals are without the knowledge and advanced training needed to address AOD-related problems effectively. The goal of this study, designed to address this critical workforce shortage, is to advance the AOD-related knowledge and teaching skill of health professions educators.
Francesca Seta, MSC, PhD
Sirtuin-1 Against Aortic Aneurysm
This CTSI Pilot grant will support crucial studies in Dr Seta’s laboratory that will examine the potential therapeutic effects of the protein sirtuin-1 in preventing aortic aneurysms by activating anti-inflammatory and anti-oxidant pathways in the vasculature. If these preclinical studies in animal models and human vascular cells will prove successful, sirtuin-1 activators could translate into novel therapies for the treatment and prevention of aortic aneurysms, a life-threatening vascular disease for which, currently, there are very limited therapeutic options.
Sam Thiagalingam, MS, PhD
Sensitization of Chemotherapy Resistant Metastatic Colon Cancer
Dr. Thiagalingam’s pilot grant proposal outlines a strategy to identify and target molecular mediators that promote colon cancer metastasis and resistance to common chemotherapeutic agents correlating to the loss of function of SMAD4, to restore sensitivity to chemotherapy.
Katrina Traber, MS, MD, PhD
Neutrophil Heterogeneity in Pneumonia
We will use flow cytometry cell sorting and next generation RNA sequencing of individual cells in a murine model of pneumonia to test the hypothesis that neutrophils recruited to the alveolar space are biologically distinct from the pulmonary circulation and that within these two groups, subpopulations can be distinguished transcriptomally.
Susan Winandy, PhD
New Pathway Regulating the Harmful Inflammatory Phenotype of T cells
Uncontrolled inflammation underlies diseases such as diabetes, asthma, rheumatoid arthritis, multiple sclerosis, Crohn’s disease and inflammatory bowel disease. Using a mouse model, we have identified a protein critical to repression of the inflammatory program in T cells. With the help of the CTSI pilot award, we will translate what we have learned into human T cells. We hope that these studies will define new pathways that are deregulated in inflammatory and autoimmune diseases, leading to new therapies
Chen Yang, MD
Inspired by the hierarchically organized axon bundles in the spinal cord white matter, we propose a nanoladder scaffold, composed of micrometer-wide fibers to provide directional guidance to the regenerated neurons, and nanometer-scale protrusions on each fiber serving as topographical cues to stimulate neurite outgrowth and synapse formation. We aim at developing a silk-based 3D nanoladder scaffold and demonstrate its efficacy in promoting axonal outgrowth and regeneration in a directional manner to promote functional restoration after spinal cord injuries.