My research in the Garcia Lab is focused on understanding the molecular mechanisms that drive Notch signaling. The Notch pathway is a cell-to-cell communication system that plays a central role in cell fate determination and cancer. Notch receptors transduce signals upon engagement with ligands Jagged or Delta-like (DLL). Until recently, structural information describing Notch-ligand complexes was unobtainable due to their intrinsically low binding affinity. We overcame this obstacle by using directed evolution to affinity-mature the Notch-DLL interaction, which allowed us to capture a stable complex for crystallization. The resulting structure explains the role of essential Notch regulatory mechanisms such as tuning of receptor specificity by O-linked glycans. We are now using this newly acquired structural information to develop novel Notch agonists and antagonists to treat cancer.
Honors & Awards
Irvington Postdoctoral Fellowship, Cancer Research Institute (July 2013-present)
Stanford Immunology Training Grant (T32), NIH (April 2013-June 2013)
Woodrow Wilson Fellowship, Johns Hopkins University (2001-2005)
Bachelor of Arts, Johns Hopkins University (2005)
Doctor of Philosophy, Washington University (2012)
Chris Garcia, Postdoctoral Faculty Sponsor