School of Medicine
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A Dale Kaiser
Jack, Lulu and Sam Willson Professor of Biochemistry, Emeritus
Current Research and Scholarly Interests How are genes regulated to construct a developmental program? How do signals received from other cells change the program and coordinate it for multicellular development? The approach taken by our laboratory group to answer these questions utilizes biochemistry and genetics; genetics to isolate mutants that have particular defects in development and biochemistry to determine the molecular basis of the defects. We study swarming in Myxococcus xanthus that builds fruiting bodies.
Wells H. Rauser and Harold M. Petiprin Professor in the School of Engineering and Professor of Chemistry and, by courtesy, of Biochemistry
Current Research and Scholarly Interests Research interests in this laboratory lie at the interface of chemistry and medicine.
For the past several years, we have investigated the catalytic mechanisms of modular megasynthases such as polyketide synthases, with the concomitant goal of harnessing their programmable chemistry for preparing new antibiotics. Recent accomplishments include methods for heterologous production of polyketides; genetically reprogrammed biosynthesis of anthraquinones and polypropionates; and chemo-biosynthesis of new polyketides not readily affordable by synthetic or biological methods alone. These methodologies are already finding practical use. At the same time, we have placed a major emphasis on the biochemistry and structural biology of these giant protein assemblies. Fundamental insights into assembly line biosynthetic mechanisms have emerged, including the finding that protein-protein interactions play a central role in intermodular communications. In turn, these insights are highlighting opportunities for enhancing the efficiency of biosynthetic engineering. Over the next decade we envision that the predictive power of polyketide biosynthetic engineering will mature analogous to current protein engineering capabilities.
More recently, we have investigated the pathogenesis of celiac sprue, an HLA-DQ2 associated autoimmune disease of the small intestine that is induced by exposure to gluten from foodgrains such as wheat, rye and barley. Within the past few years, we have explored three potential therapeutic strategies for this widespread but overlooked disease. By dissecting the unique chemical features of gluten, we discovered an intimate link between proteolytic stability and immunotoxicity of gluten, and translated this knowledge into the design of an oral enzyme therapy for the disease. At the same time, we have synthesized and evaluated mechanism-based inhibitors of human transglutaminase 2, the predominant disease associated auto-antigen. Finally, our structural and mechanistic dissection of HLA-DQ2 has been used to design, synthesize and evaluate gluten peptide analogues that selectively inhibit disease associated T cells. We remain committed to the vision that, within the next decade, safe and effective drugs will start having measurable impact on the health of celiac sprue patients.
Peter S. Kim
Virginia and D. K. Ludwig Professor of Biochemistry
Current Research and Scholarly Interests We are studying the mechanism of viral membrane fusion and its inhibition by drugs and antibodies. We use the HIV envelope protein (gp120/gp41) as a model system. Some of our studies are aimed at creating an HIV vaccine. We are also characterizing protein surfaces that are referred to as "non-druggable". These surfaces are defined empirically based on failure to identify small, drug-like molecules that bind to them with high affinity and specificity.
Professor of Biochemistry
Current Research and Scholarly Interests - Lung development and stem cells
- Neural circuit of breathing
- Lung diseases including lung cancer
- New genetic model organisms for medicine