The candidate has a Ph.D. in Biophysics and has completed clinical training in cardiology. He is now pursuing basic research with a long-term career goal of being an independent investigator. The candidate's mentor is Professor Stuart Schreiber of the Department of Chemical Biology at Harvard University. The Schreiber laboratory is a world leader in using chemistry to understand biological processes; the candidate hopes to advance his training in chemistry and chemical genetics while studying vascular development. Improper regulation of new blood vessel growth contributes to the pathophysiology of illnesses such as heart disease and cancer. Recent descriptions of bone marrow-derived and circulating endothelial progenitor cells have rekindled interest in how endothelial precursors become incorporated into post-natal vessels. This behavior is reminiscent of how embryonic endothelial precursors (angioblasts) coalesce to form the early vessels of the vertebrate embryo. Thus, studies of embryonic vascular development may inform our understanding of post-natal vessel formation. The zebrafish mutant gridlock features abnormal development of the aorta and resembles aortic coarctation in humans. A small molecule GS4012 has been identified that suppresses the gridlock phenotype and also increases VEGF expression in zebrafish and cultured HUVECs. This proposal seeks to (i) determine the mechanism of GS4012's in vivo suppression of the gridlock phenotype, (ii) use HUVECs as a model system to dissect signaling pathways modulated by GS4012, and (iii) identify its target protein using an affinity purification approach. By elucidating the mechanism of action of GS4012, we hope to identify signaling pathways important for embryonic vascular development and post-natal angiogenesis. This may in turn lead to novel therapies for ischemic vascular disease and other important conditions.
| Chong, Nelson W; Koekemoer, Andrea L; Ounzain, Samir et al. (2012) STARS is essential to maintain cardiac development and function in vivo via a SRF pathway. PLoS One 7:e40966 |
| Shaw, Stanley Y; Brettman, Ari D (2011) Phenotyping patient-derived cells for translational studies in cardiovascular disease. Circulation 124:2444-55 |
| Shaw, Stanley Y; Blodgett, David M; Ma, Maggie S et al. (2011) Disease allele-dependent small-molecule sensitivities in blood cells from monogenic diabetes. Proc Natl Acad Sci U S A 108:492-7 |
| Tassa, Carlos; Duffner, Jay L; Lewis, Timothy A et al. (2010) Binding affinity and kinetic analysis of targeted small molecule-modified nanoparticles. Bioconjug Chem 21:14-9 |
| Kelly, Kimberly A; Shaw, Stanley Y; Nahrendorf, Matthias et al. (2009) Unbiased discovery of in vivo imaging probes through in vitro profiling of nanoparticle libraries. Integr Biol (Camb) 1:311-7 |
| Shaw, Stanley Y; Westly, Elizabeth C; Pittet, Mikael J et al. (2008) Perturbational profiling of nanomaterial biologic activity. Proc Natl Acad Sci U S A 105:7387-92 |
