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Robert Lazarus Principal Scientist: Protein Engineering |
"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. General areas of interest include characterization of proteins involved in various pathways of cancer biology and inflammation, enzymology of serine proteases, protease inhibitors, deoxyribonucleases, and application of diversity technologies such as phage display. My lab utilizes proteins, peptides and antibodies as molecular tools and a variety of technologies to study these interactions. I also have interests in studying allosteric enzyme inhibitors as alternatives to traditional active site inhibitors. 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 work within an interdisciplinary group integrating technologies from protein engineering including molecular biology, protein expression/purification from E. coli, insect or mammalian cells, site-directed mutagenesis, enzyme kinetics, ELISA, surface plasmon resonance, phage display, protein biochemistry, structural biology and cell biology.
Specific projects have focused on understanding the mechanism of HGF/Met receptor tyrosine kinase signal transduction implicated in tumorigenesis and metastasis, investigating protein/protein interactions in the Hedgehog pathway of developmental biology and cancer, type II transmembrane serine proteases and prolyl peptidases linked to cancer, engineering improved versions of DNase I with increased enzymatic activity for cystic fibrosis, developing exosite inhibitors of coagulation Factor VIIa as protease inhibitors and anticoagulants, exploring Kunitz domains as scaffolds for protease inhibition, characterizing GPIIb-IIIa integrin antagonists from snake venoms and leeches as platelet aggregation inhibitors and microbial pathway engineering for bioconversion of glucose to vitamin C."