Please join us for the third Michael Jaharis Symposium, with speaker Dr. Jim Wells from the University of California, SF, presenting his talk: “Pirating Biology to Probe and Attack the Cancer Surfaceome”
Join us afterwards in the Ford Hive Annex for a reception with refreshments.
Abstract:
The cell surface proteome (surfaceome) is a major hub for cellular communication and a primary source of drug targets, especially for biologics. Dr. Wells’ lab is interested in developing proteomic means to probe how the surfaceome changes in health and disease, especially cancer. Such changes involve alteration in protein expression and post-translational modifications such as proteolysis. He will describe new engineered tools they have built to probe the surfaceome changes that occur when oncogenes are expressed in isogenic cell lines to identify targets of interest. They then target proteins either upregulated, proteolyzed, or both with recombinant antibodies derived by phage display to be used as validation tools and potential therapeutic leads.
Bio:
Jim Wells received his BA degrees in biochemistry and psychology from the University of California, Berkeley, and a PhD in biochemistry from Washington State University with Ralph Yount. He completed his postdoctoral studies at Stanford University School of Medicine with George Stark. He began his independent research career as a cofounding member of the Protein Engineering Department at Genentech. At Genentech, Wells and his group pioneered “gain-of-function engineering” of enzymes (such as subtilisin), growth factors (hGH), and antibodies by site-directed mutagenesis and protein phage display. Several biologic products derived directly from these efforts including Pegvisomat (Somavert), an engineered growth hormone antagonist for treatment of acromegaly; humanization of the Bevacizumab (Avastin), a VEGF antagonist for treating cancers; and engineered proteases sold in laundry detergents today.
Wells then cofounded Sunesis Pharmaceuticals, where he was CSO and president. At Sunesis, the group developed a novel technology for site-directed fragment-based drug discovery, Tethering®, and applied it to cancer targets. They were among the first to develop potent small molecules to protein interfaces and cryptic allosteric sites considered undruggable. Several of the compounds discovered with Tethering are now in clinical development. They also discovered the anti-inflammatory drug Lifitegrast, which was subsequently developed by SarCODE and is now sold by Shire for dry eye syndrome.
In 2005, Wells joined the faculty of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology at UCSF. He founded the Small Molecule Discovery Center and served as chair of Pharmaceutical Chemistry. He has cofounded several other companies, most recently EpiBiologics, which is focused on developing extracellular degraders to remove disease causing proteins.
The Wells Lab now investigates how cell surface proteomes change in health and disease by applying mass spectrometry and protein and antibody engineering to understand and disrupt human-disease-associated signaling processes. Cell surface proteomics is the study of cell surface proteins or “the surfaceome,” which is essential to understand how expression levels and post-translational modifications change from healthy to diseased cells. More than 70 percent of modern pharmaceuticals target cell surface proteins. For this reason, proteomic profiling of cell surface proteins has become increasingly popular and conducive to the discovery of new biomarkers and drug targets. The Wells Lab uses cutting-edge proteomics and gene silencing to understand how and why the cell surfaceome is remodeled in diseases like cancer. They then employ an industrialized phage-antibody platform to build antibodies to detect, modulate, and attack disease-related surface proteins on cells and in animals.
Wells is the recipient of a number of societal awards including being elected member of the National Academy of Sciences, the National Academy of Inventors, and the American Association for the Advancement of Sciences.
