Jim has pioneered the engineering of proteins, antibodies, and small molecules that target catalytic, allosteric, and protein-protein interaction sites. He innovated 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 and protein-Seq. These lead to important new insights into protease mechanisms, growth factor signaling, hot-spots in protein-protein interfaces, role of caspases in biology, and more recently determining how cell surfaces change in health and disease. He was an integral part of teams that engineered several protein products sold by biotechnology companies today including Genentech (Avastin), Genencor (engineered proteases), and Pfizer (Somavert). He joined Genentech in 1982 as one of the founding members of the Protein Engineering Department, Founded Sunesis Pharmaceuticals in 1998 and joined UCSF in 2005 now as Professor and former Chair of Pharmaceutical Chemistry. In 1999 he was elected member of the National Academy of Sciences, 2015 elected member in the American Association of Arts and Sciences, and 2016 the National Academy of Inventors.