Bob Lazarus

Principal Scientist, Early Discovery Biochemistry

POSTDOC MENTOR

"Genentech has been an incredibly exciting place to work. I love the opportunity to tackle complex biochemical, biological and medical problems in a multidisciplinary environment where I can collaborate with expert scientists with such diverse backgrounds. Great science, great people.”"

• 31
  years at Genentech
• 10
  publications (2010-12)

I started working at Genentech in 1983 after my PhD and postdoctoral studies in bioorganic chemistry and mechanistic enzymology. I initially worked on biocatalysis (bioconversion to make vitamin C) followed by GP IIbIIIa antagonists from naturally occurring proteins as platelet aggregation inhibitors. I then developed interests in protein-protein interactions, DNase I enzymology, peptide and protein scaffolds and protein engineering technologies to interrogate key biological pathways with activators or inhibitors. I have focused on proteases, pseudoproteases and other targets using protein/peptide structure and function to guide molecular and diversity approaches within a multidisciplinary group generating tools for drug development in diverse biological areas.

• My Focus

  My lab works on fundamental and applied aspects of protein engineering in order to investigate molecular, biochemical and biological aspects of protein/protein and protein/ligand interactions. My goal is to understand biochemical and biological mechanisms and to develop specific agonists or antagonists as tools for specific intervention in the biological pathway of interest. I also have interests in studying allosteric enzyme inhibitors and exosites as alternatives to traditional inhibitors and active sites.

  General areas of interest include characterization of proteins involved in various pathways of cancer biology and inflammation, infectious disease, neurobiology, serine proteases and pseudoproteases, deoxyribonucleases, and application of diversity technologies such as phage display. My lab utilizes peptides, proteins and protein scaffolds as molecular tools and various technologies to study these interactions. Specific systems include HGF/Met, BACE1, Hedgehog, MSP/RON, DNase I and Factor VIIa.

• Publications

  • The Structure of Human DNase I Bound to Magnesium and Phosphate Ions Points to a Catalytic Mechanism Common to Members of the DNase I-like Superfamily

    Biochemistry, 2012, ISSN:

    Parsiegla, Goetz; Noguere, Christophe; Santell, Lydia; Lazarus, Robert; Bourne, Yves;

     View on PubMed

  • Proteolytic activation of pro-macrophage-stimulating protein by hepsin

    Molecular Cancer Research, 29 Aug 2011, ISSN: 1557-3125.

    Ganesan, Rajkumar; Kolumam, Ganesh A; Lin, S Jack; Xie, Ming Hong; Santell, Lydia; Wu, Thomas D; Lazarus, Robert A; Chaudhuri, Amitabha; Kirchhofer, Daniel

     View on PubMed

  • A Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-β Production in Vivo.

    Science Translational Medicine, 2011, ISSN: 1946-6234

    Atwal, J.K.; Chen, Y.; Chiu, C.; Mortensen, D.L.; Meilandt, W.J.; Liu, Y.; Heise, C.E.; Hoyte, K.; Luk, W.; Lu, Y.; Peng, K.; Wu, P.; Rouge, L.; Zhang, Y.; Lazarus, R.A.; Scearce-Levie, K.; Wang, W.; Wu, Y.; Tessier-Lavigne, M.; Watts, R.J.

     View on PubMed

  • Allosteric Peptide Activators of Pro-Hepatocyte Growth Factor Stimulate Met Signaling.

    The Journal of Biological Chemistry, 2010, ISSN: 0021-9258

    Landgraf, K.E.; Santell, L.; Billeci, K.L.; Quan, C.; Young, J.C.; Maun, H.R.; Kirchhofer, D.; Lazarus, R.A.

  • Interactions between Hedgehog proteins and their binding partners come into view.

    Genes & Development, 2010, ISSN: 0890-9369

    Beachy, P.; Hymowitz, S.; Lazarus, R.; Leahy, D.; Siebold, C.;

  • Pseudo-active sites of protease domains: HGF/Met and Sonic hedgehog signaling in cancer.

    Biological Chemistry, 2010, ISSN: 1437-4315

    Maun, H.; Kirchhofer, D.; Lazarus, R.

  • Hedgehog Pathway Antagonist 5E1 Binds Hedgehog at the Pseudo-active Site.

    The Journal of Biological Chemistry, 2010, ISSN: 1083-351X

    Maun, H.; Wen, X.; Lingel, A.; de Sauvage, F.; Lazarus, R.; Scales, S.; Hymowitz, S.

  • Bi-directional SIFT predicts a subset of activating mutations.

    PLoS ONE, 2009, ISSN: 1932-6203

    Lee, W.; Zhang, Y.; Mukhyala, K.; Lazarus, R.A.; Zhang, Z.

  • The structure of SHH in complex with HHIP reveals a recognition role for the SHH pseudo-active site in signaling.

    Nature Structural & Molecular Biology, 2009, ISSN: 1545-9985

    Bosanac, I.; Maun, H.R.; Scales, S.J.; Wen, X.; Lingel, A.; Bazan, J.F.; de Sauvage, F.J.; Hymowitz, S.G.; Lazarus, R.A.

  • Noncompetitive inhibition of hepatocyte growth factor-dependent Met signaling by a phage-derived peptide

    Journal of Molecular Biology, 2009, ISSN: 0022-2836

    Tam, E.M.; Runyon, S.T.; Santell, L.; Quan, C.; Yao, X.; Kirchhofer, D.; Skelton, N.J.; Lazarus, R.A.

• Education
  • The Pennsylvania State University, Chemistry, Ph.D. – 1979
  • The Pennsylvania State University, Postdoctoral Research – 1979-1982
  • Lehigh University, Chemistry, B.S. – 1974