Brian Shoichet, PhD
|School||UCSF School of Pharmacy|
|Address||1700 4th St|
San Francisco CA 94158
|University of California, San Francisco||Ph.D.||1991|| Graduate Division (Pharmaceutical Chemistry)|
||1996||Damon Runyon-Walter Winchell Cancer Research Fellow|
||1999||Career Development Award|
|National Science Foundation||1998
|Northwestern University||2001||Dean’s Award for Teaching Excellence|
|University of Ottawa||2004||Astra Lectureship|
||2007||Novartis Chemistry Lecturer (Cambridge, Basel, Vienna, Horsham, Tsukuba, Emeryville)|
|2008||Swiss Universities 3e Cycle en Chimie (Lausanne, Bern, Friborg, Geneva)|
|Yale University||2009||Abbott Lectureship|
|2011||Society for Biomolecular Sciences Accomplishment Award|
|University of Michigan||2011||Topliss Lectureship|
The Shoichet lab seeks to discover chemical reagents that can illuminate biological problems. A longstanding effort to do so is by exploiting protein structures to predict new reagents and therapeutic leads (structure-based ligand discovery). Two ongoing projects are 1. Developing new computational methods for ligand discovery and 2. Applying these to G-Protein Coupled Receptors (GPCRs), which are the single largest family of signaling receptors in human cells.
Allied with this effort is an experimental research program that 3. Tests the new methods in well-controlled systems, determining x-ray crystal structures and measuring binding thermodynamics. The experimental program has led to unexpected discoveries, including the observation that many drugs and reagents can form colloidal aggregates in solution. This has led us to investigate 4. How the physical organic chemistry of drugs affects their behavior in vitro and in vivo, influencing drug delivery and formulation.
A new effort turns the entire structural view on its head, 5. Developing computational methods to relate receptors by the similarity of their ligands, rather than by protein sequence or structure. This changes pharmacological relationships dramatically—targets that would normally be considered sequence neighbors are pushed far apart (because their ligands are dissimilar), whereas other targets that supposedly have nothing to do with one another become neighbors (because their ligands are very similar). Since the new relationships are articulated by ligands, they may be directly tested both on isolated receptors and, increasingly, against model whole organisms, such as zebra fish, C. elegans and mice. This project seeks to discover the integrated chemical circuits through which drugs and reagents affect whole organisms. "
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