Plenary Keynote Program

Join colleagues from around the world for the Discovery on Target Plenary Keynote Program. Bridging both halves of the event, it's the only time our whole community of drug discovery professionals assembles together to learn about big-picture perspectives, innovative technologies, and thought-provoking trends from luminaries in the field.


James A. WellsPirating Biology to Detect and Degrade Extracellular Proteins
James A. Wells, PhD, Professor, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California, San Francisco
In contrast to intracellular PROTACs, approaches to degrade extracellular proteins are just emerging. I’ll describe our recent progress to harness natural mechanisms such as transmembrane E3 ligases to degrade extracellular proteins using fully genetically encoded bi-specific antibodies we call AbTACs. We have also engineered a peptide ligase which can be tethered to cells to detect proteolysis events and target them with recombinant antibodies for greater selectivity for the tumor microenvironment.

Wells’s group pioneered the engineering of proteins, antibodies, and small molecules that target catalytic, allosteric, and protein-protein interaction sites; technologies including protein phage display, alanine-scanning, engineered proteases for improved hydrolysis, bioconjugations, N-terminomics, disulfide “tethering” (a novel site-directed fragment-based approach for drug discovery); and more recently an industrialized recombinant antibody production pipeline for the proteome. These led to important new insights into protease mechanisms, growth factor signaling, hot-spots in protein-protein interfaces, role of caspases in biology, and more recently to determining how cell surfaces change in health and disease. His team was integral to several protein products, including Somavert for acromegaly, Avastin for cancer, Lifitegrast for dry eye disease, and engineered proteases sold by Pfizer, Genentech, Shire and Genencor, respectively. He is an elected member of the US National Academy of Science, American Association of Arts and Science, and the National Academy of Inventors.

Additional Plenary Keynote Speaker to be Announced