Professor Mark Grinstaff and postdoctoral scientist, Dr. Aaron Colby, have received a 2015 Ignition Award from the BU Office of Technology Development to develop a nanoparticle-based drug delivery system for the treatment of mesothelioma. Mesothelioma is a rare form of cancer that develops from cells of the mesothelium, the protective lining that covers many of the internal organs of the body.
The purpose of the Ignition Awards program is to validate early-stage projects with clear commercial and medical potential. This project was selected because, to date, there is no effective cure for mesothelioma and there is no way to prevent local recurrence. In this research, the Grinstaff group is developing a novel nanoparticle-based drug delivery system for localizing intraperitoneally administered chemotherapy directly to the site of established disease that remains following surgical resection procedures. The result is increased tumor-tissue drug concentrations and, subsequently, reduced recurrence and improved patient survival.
Since its establishment in 2007, the Ignition Awards Program has funded 46 project. Of these projects, 10 have been developed by Chemistry faculty.
We are happy to announce that Arturo José Vegas will be joining the Department on July 1 as Assistant Professor. His research will aim to develop novel targeting therapeutics and delivery systems for selective cancer chemotherapy, immunomodulation, and diabetic immunosuppression. At the same time, the Vegas laboratory will create a general and systematic approach to developing targeted therapeutic carriers for treating multiple human diseases.
Arturo Vegas brings his unique training and experience in integrating chemistry and the biomedical sciences to come to bear on key challenges in medicine. He received his Ph.D. from Harvard University (2008) working with Professor Stuart Schreiber (Department of Chemistry & Chemical Biology). In the Schreiber laboratory, he adapted synthetic chemistry pathways developed in studies of diversity-oriented synthesis (DOS) to new pathways with clinical impact for cancer treatments aimed at targeting chromatin-modifying enzymes in human cells.
His postdoctoral training was in the laboratories of Professor Robert S. Langer and Professor Daniel G. Anderson both at the David H. Koch Institute for Integrative Cancer Research at MIT and Children’s Hospital Boston. Dr. Vegas’ research exploited the potential of chemical discovery in biomedical research. He applied chemical methods to modify polymers used in the encapsulation of islets, which is a promising approach for the treatment of type-1 diabetes. As a synthetic chemist, he prepared multiple libraries and unique chemical entities to facilitate siRNA delivery, a technology that is actively being explored for cancer treatment.
Dr. Vegas is already co-author on 20 publications and co-inventor of 8 patent applications as he begins his independent career at Boston University. He is also the Scientific Co-Founder of Preceres LLC (December 2013). His research was featured in Nature Medicine’s “Encapsulate This” (2014). As an educator, he was a multiple-year recipient of Harvard University’s “Distinction in Teaching” Award.
The College of Engineering has honored interdisciplinary scientist, Professor Mark Grinstaff (Chemistry, BME, MSE, MED), with the inaugural Charles DeLisi Award and Distinguished Lecture. Professor Grinstaff will present the Lecture on Thursday, April 2 at 4 p.m. in the Photonics Colloquium Room (PHO 906). In the lecture, “Clinically Informed Biomaterial Design and Engineering,” he will explore how over the past two decades, he and his students have translated ideas from the laboratory into new devices and materials for clinical applications.
The award – established by a generous gift by Professor and Dean Emeritus Charles DeLisi, widely considered the father of the Human Genome Project – is in recognition of Mark Grinstaff’s significant contributions to his field, both as an academic researcher and as an entrepreneur who has co-founded four companies that are translating his ideas into clinical products. In addition to his joint appointments in Chemistry and Biomedical Engineering, Professor Grinstaff directs the Center for Nanoscience and Nanobiotechnology (CNN) and an NIH-funded Translational Research in Biomaterials Training program, and is the inaugural College of Engineering Distinguished Professor of Translational Research and inaugural recipient of the Innovator of the Year Award from BU’s Office of Technology Development. He was also named a College of Engineering Distinguished Faculty Fellow and a Kern Faculty Fellow.
The Grinstaff laboratory, which is currently comprised of more than 20 graduate students and postdoctoral fellows, is funded by the National Institutes of Health, National Science Foundation, The Wallace H. Coulter Foundation, Advanced Energy Consortium, the Center for Integration of Medicine & Innovative Technology, and other agencies. They have advanced several major biomaterials that range from a joint lubricant that could bring longer- lasting relief to millions of osteoarthritis sufferers, to a highly absorbent hydrogel that not only seals wounds, but can later be dissolved and gently removed.
The National Science Foundation’s on line magazine, Science Nation, is featuring a video entitled “Biophotonics poised to make major breakthroughs in medicine.”
Focusing on the Boston University Center for Biophotonic Sensors and Systems (CBSS), the video shows how engineers and scientists collaborate with industry to realize the potential of light waves in the diagnosis and treatment of disease. Among the scientific work highlighted is that of Chemistry professor, Larry Ziegler, and his group who are working with the company, BioTools, to develop a test that uses lasers to diagnose a bacterial infection accurately and quickly.
“Science Nation” is a video series commissioned by the NSF Office of Legislative and Public Affairs. The series is distributed throughout the world, including to LiveScience.com and other media outlets on the Internet, the PBS Newshour Science page, local community TV stations in the U.S. via TelVue Connect Media Exchange, Voice of America for international broadcast distribution, the NSF STEM video portal Science360, the Knowledge Network video stream and Roku channel, and K-12 content distributors in the U.S. and abroad. Some episodes also appear in the nationally-distributed PBS documentary series This American Land.
The Schlumberger Foundation Faculty for the Future Fellowship funds women from emerging economies for advanced post‐graduate study in the fields of science, technology, engineering and mathematics (STEM) in the finest universities for their discipline overseas with the long term goal of addressing the worldwide gender gap in STEM disciplines. A highly competitive program, the Foundation selects talented female scientists with the potential to become future leaders, change agents, and policy makers in their home regions. In 2012, Dr. Laura Dominguez, a native of Mexico, received a Schlumberger Foundation postdoctoral fellowship and selected the Straub group under the leadership of Professor John Straub as the site of her training and research. In the Straub lab, the objective of Laura’s postdoctoral work was to exploit the growing power of computer simulations to help understand the causes and mechanism of protein aggregation inside cells. Knowledge of the detailed process of protein aggregation is crucial for understanding the development of illnesses such as amyloidosis and neurodegenerative disease, how and why aggregation occurs, and what could be done to prevent it.
Completing her fellowship in 2014 with five publications with the Straub group, Dr. Dominguez attended the Schlumberger forum in November 2014 where, in Laura’s words, she had “the opportunity to hear a lot about the diverse research and experiences from other women mainly from Africa, Eastern Europe and Asia.” While the agenda called for an end of the forum at 5 pm each day, the enthusiastic participants continued their discussions well past midnight, sharing their views on the talks given by distinguished representatives from UNICEF, as well as successful women in the sciences and technology. Dr. Dominguez facilitated the timely discussion on “Poverty & STEM.”
Laura Dominguez studied chemistry at the Universidad Nacional Autónoma de México (UNAM) in Mexico City as an undergraduate and received a Masters degree in Biochemistry from that institution. Her career goal was always to become a Professor at UNAM, which she proudly considers to be the most prestigious university in Mexico. Thanks to her education and continued excellent training in the Straub group as a Schlumberger postdoctoral fellow, that is exactly what Dr. – now Professor -‐ Dominguez has accomplished.
The National Institutes of Health (NIH) has awarded a 4-year grant to computational chemists, Professor John Straub and his colleague at the University of Maryland (UMD), Professor Devarajan (Dave) Thirumulai, on “Probing the role of membrane and cholesterol on APP‐C99 structure and dynamics.” Protein aggregation in the brain is linked to Alzheimer’s Disease (AD). This neurodegenerative disorder accounts for nearly 50 percent of all cases of senile dementia, is the third leading cause of death in the elderly population, and – devastatingly ‐ is presently incurable. Familial mutations in the Amyloid Precursor Protein (APP), from which the amyloid β (Aβ) protein associated with AD is derived, have been linked with the early onset of amyloid disease.
This computational and theoretical research collaboration between the Straub and Thirumalai groups, augmented by synergistic experimental research collaborations, will explore the structure and dynamics of the 99 amino acid transmembrane fragment of APP (APP‐C99) in membrane environments. This work will have high impact because it has the potential to answer outstanding questions in the field that remain unresolved as a result of conflicting conclusions of experimental studies. By providing novel insights into the dependence of APP structure on familial AD mutations, membrane composition, and interactions with cholesterol, the work will advance the ability to develop preventive or early stage therapeutics for AD.
A publication from the research group of Professor Adrian Whitty has been selected by the Journal of Biological Chemistry (JBC) as “Paper of the Week.” This distinction is conferred upon JBC papers that the Associate Editors and Editorial Board Members consider to represent the “top 2% of JBC papers in overall importance.” The paper, “Quantitative Analysis of Receptor Tyrosine Kinase-Effector Coupling at Functionally Relevant Stimulus Levels,” provides a rare, quantitative view of how activation of a growth factor receptor is linked to signaling and function. The work is significant because it sheds new light on some of the factors that determine what concentration of growth factor is required to achieve a functional response, and how this functional sensitivity relates to the dose-response behavior observed for receptor activation and for intracellular signaling events. The paper also shows that experiments done using high ligand concentrations can obscure quantitative features of receptor signaling. The journal will publish a profile of the paper’s first author, 5th year graduate student Simin Li (pictured). Other Whitty group investigators who contributed to the work include Dr. Devayani Bhave and Dr. Thomas Riera (former Postdoctoral Fellows), Jennifer Chow and Mariya Atanasova (graduate students), Simone Rauch (undergraduate student), and Dr. Richard Cate (Visiting Scientist).
The high-impact science journal, Nature Chemistry, has published a paper by Professor John A. Porco, Jr., and his colleagues reporting on “Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer” (2 February 2015). Rugulotrosin A is a symmetric dimer isolated from an uncharacterised species of Penicillium. The compound displays significant antibacterial activity against a wide range of Gram positive bacteria. Investigating this important compound, the project was conceived by former Porco Group graduate student, Dr. Tian Qin (now a Postdoctoral Associate in the Baran Laboratory at Scripps Research Institute) and Professor Porco. Collaborators for the project included Professor Richard P. Johnson and his colleague Sarah L. Skrabe-Joiner at the University of New Hampshire (Durham, NH) who performed computational studies and Professor Robert J. Capon and Dr. Zeinab Khalil of the Institute of Molecular Bioscience at the University of Queensland (Australia) who carried out natural extract comparisons and biological studies.
Overall, the project team developed a concise, atropselective approach to rugulotrosin A and stereoisomers through point-to-axial chirality transfer which facilitated determination of the absolute configuration of rugulotrosin A. Computational studies modelling the geometry of intermediate diaryl Pd(II) complexes provided a rationale for the atropselectivity observed in the key Suzuki dimerization. Through HPLC analysis of fungal extracts and synthetic samples, it was determined that Penicillium nov. sp. (MST-F8741) generates rugulotrosin A in an atropselective manner. Moreover, the atropisomers and enantiomers of rugulotrosin A were found to have different activities against Gram-positive bacteria, illustrating the importance of stereochemistry on target selectivity.
The cornerstone of organic synthesis is the development of novel chemical methodology that addresses key limitations in efficiency and reactivity. These synthetic methodologies are best demonstrated in the synthesis of biologically relevant molecules such as current drugs and compounds of study. The goal of this 5-year NIH-funded research program being conducted by Professor Scott Schaus and his Group is to develop operationally simple, highly effective methods for constructing building blocks using boron-containing carbon compounds.
The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. The Schaus Research Laboratory will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. The majority of top selling drugs are sold as a single enantiomer or isomer. The asymmetric construction of pharmaceuticals becomes increasingly more challenging. As it becomes a greater health concern, so will the need for novel methods and chemical substances that prevent and treat human disease.
The newly configured Center for Molecular Discovery (CMD) builds on the legacy of Boston University’s NIH-funded Center of Excellence, the Center for Chemical Methodology and Library Development (2002-2007 and 2008-2013) to create a new functional core with a focus on the development of small molecule probes and therapeutic leads.
Integrating its small molecule screening collection and medicinal chemistry capabilities with the efforts of high-impact researchers in the biomedical field, the CMD is an enabling core resource for advancing translational science at Boston University.
The CMD will continue to engage in high-throughput screening (HTS) and medicinal chemistry collaborations with external researchers as part of the Chemical Library Consortium (CLC) network formed by the CMLD. The Center has new and ongoing collaborations with several research groups on the BU Charles River Campus, the BU School of Medicine, and the National Emerging Infectious Diseases Laboratories. While some of these collaborations are in early stages, others have progressed to the point of early proposal development, proposal submission, and extramural funding. The CMD has also developed collaborations with companies (e.g., Cubist, AstraZeneca, and Vertex) and scientists at other research universities to further leverage its compound collection.