Robert A. Lazarus

Robert A. Lazarus (Genentech, South San Francisco, CA, USA)

 Resume: Robert Lazarus has a PhD in Chemistry and has been at Genentech since 1983 and is a Principal Scientist in the Department of Early Discovery Biochemistry. He has worked on a wide variety of projects focused on fundamental and applied aspects of protein engineering to investigate molecular, biochemical and biological aspects of protein/protein and protein/ligand interactions. Areas explored include characterization of proteins involved in cancer biology and inflammation, serine proteases and their inhibitors, DNase I, and application of phage display technologies. He has published almost 100 papers in journals and books and is currently President of the International Proteolysis Society.

Noncanonical Modulators of BACE1 Activity for Alzheimer’s Disease

The formation of b-amyloid plaques is a hallmark of Alzheimer’s Disease (AD). These are formed from fibrillar deposits of Ab peptides, derived from amyloid precursor protein following sequential proteolysis by the b- and g-secretases. Inhibition of the b-secretase BACE1, a membrane-bound aspartic acid protease, is an attractive target as it represents the first step in the pathway. We have identified and characterized different classes of peptides and antibodies that bind to BACE1 using phage display. Biochemical and biological studies as well as structures of both peptide and antibody complexes provide insights into their mechanisms of action and potential for AD.