Chaitan Khosla
Chaitan Khosla
Director, ChEM-H, Wells H. Rauser and Harold M. Petiprin Professor in the School of Engineering and Professor of Chemistry and, by courtesy, of Biochemistry
Antibiotic biosynthesis and engineering; chemical foundations of inflammation
About
Research in this laboratory focuses on problems where deep insights into enzymology and metabolism can be harnessed to improve human health.
For the past two decades, we have studied and engineered enzymatic assembly lines called polyketide synthases that catalyze the biosynthesis of structurally complex and medicinally fascinating antibiotics in bacteria. An example of such an assembly line is found in the erythromycin biosynthetic pathway. Our current focus is on understanding the structure and mechanism of this polyketide synthase. At the same time, we are developing methods to decode the vast and growing number of orphan polyketide assembly lines in the sequence databases.
For more than a decade, we have also investigated the pathogenesis of celiac disease, an autoimmune disorder of the small intestine, with the goal of discovering therapies and related management tools for this widespread but overlooked disease. Ongoing efforts focus on understanding the pivotal role of transglutaminase 2 in triggering the inflammatory response to dietary gluten in the celiac intestine.
Appointments
Professor, Chemical Engineering
Professor, Chemistry
Professor (By courtesy), Biochemistry
Member, Bio-X
Member, Maternal & Child Health Research Institute (MCHRI)
Member, Stanford Cancer Institute
Director, Stanford ChEM-H
Member, Wu Tsai Neurosciences Institute
Honors & Awards
Member, National Academy of Sciences (2020)
Arthur C. Cope Scholar Award, American Chemical Society (2009)
Member, National Academy of Engineering (2009)
Professional Progress Award, American Institute of Chemical Engineers (2008)
Member, American Academy of Arts and Sciences (2007)
Fellow, American Association for the Advancement of Science (2006)
Pure Chemistry Award, American Chemical Society (2000)
Alan T. Waterman Award, National Science Foundation (1999)
Eli Lilly Award in Biological Chemistry, American Chemical Society (1999)
Allan P. Colburn Award, American Institute of Chemical Engineers (1997)
Boards, Advisory Committees, Professional Organizations
Board Member, Protagonist Pharmaceuticals (2014 - Present)
Scientific Policy Committee Member, SLAC National Accelerator Laboratory (2014 - Present)
Professional Education
Postdoc, John Innes Centre, U.K., Genetics (1992)
PhD, California Institute of Technology, Chemical Engineering (1990)
Featured Publications
Lowry, B., Li, X., Robbins, T., Cane, D. E., & Khosla, C. (2016). A Turnstile Mechanism for the Controlled Growth of Biosynthetic Intermediates on Assembly Line Polyketide Synthases. ACS Central Science, 2(1), 14–20.
Edwards, A. L., Matsui, T., Weiss, T. M., & Khosla, C. (2014). Architectures of Whole-Module and Bimodular Proteins from the 6-Deoxyerythronolide B Synthase. JOURNAL OF MOLECULAR BIOLOGY, 426(11), 2229–45.
Morón, B., Verma, A. K., Das, P., Taavela, J., Dafik, L., DiRaimondo, T. R., … Makharia, G. K. (2013). CYP3A4-Catalyzed Simvastatin Metabolism as a Non-Invasive Marker of Small Intestinal Health in Celiac Disease. American Journal of Gastroenterology, 108(8), 1344–1351.
Kloeck, C., Herrera, Z., Albertelli, M., & Khosla, C. (2014). Discovery of Potent and Specific Dihydroisoxazole Inhibitors of Human Transglutaminase 2. JOURNAL OF MEDICINAL CHEMISTRY, 57(21), 9042–9064.
Lowry, B., Robbins, T., Weng, C.-H., O'Brien, R. V., Cane, D. E., & Khosla, C. (2013). In vitro reconstitution and analysis of the 6-deoxyerythronolide B synthase. Journal of the American Chemical Society, 135(45), 16809–12.
Deans, R. M., Morgens, D. W., Okesli, A., Pillay, S., Horlbeck, M. A., Kampmann, M., … Bassik, M. C. (2016). Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification. NATURE CHEMICAL BIOLOGY, 12(5), 361-?
