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| Research Domain： |
Bioorganic and Biophysical Chemistry |
| Keyword： |
Chaitan S. Khosla |
| Research Production： |
Research interests in this laboratory lie at the interface of protein 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 the biosynthesis of new, pharmaceutically relevant natural products. Examples of natural products that have been studied in our laboratory include anthraquinones such as R1128 (a selective estrogen receptor antagonist) and macrolides such as erythromycin, rifamycin (both antibacterials), and epothilone (anti-tumor agent). Most of our current efforts focus on obtaining higher resolution insights into polyketide synthase structure and mechanism, and on translating these insights into next generation tools for combinatorial biosynthesis. In particular we are interested in dissecting and manipulating two features of these multifunctional enzymes - the relative influence of protein-substrate interactions and protein-protein interactions on the specificity of each step in the overall catalytic cycle, and the highly controlled incorporation of building blocks in each round of chain extension. At the same time we also continue to develop new technologies for heterologous production of polyketides in E. coli. Finally, given the rich biology associated with polyketides, occasionally we also probe the biological properties of natural and "unnatural" natural products.
More recently, we have undertaken a project aimed at understanding and modulating the chemistry and biology of Celiac Sprue, an HLA-DQ2 associated immune disorder of the gastrointestinal tract. Celiac Sprue is an increasingly diagnosed enteropathy that is induced by dietary exposure to gluten from common food grains such as wheat, rye and barley. Notwithstanding the seriousness of the disorder, little is known about the mechanistic underpinnings of this disease. No therapeutic agents are available to counter the toxic effects of the culprit cereals, and the only treatment for Celiac sprue involves a lifelong adherence to a strict gluten-free diet. Our goals are to understand the biochemical basis of Celiac Sprue, and to translate these insights into pharmacological agents that could allow patients to safely re-incorporate these otherwise nutritious and extremely common food grains into their diet. Specifically we are exploring three therapeutic approaches: (i) peptidase therapy for rapid detoxification of proteolytically stable immunogenic epitopes in gluten; (ii) small molecule inhibitors of tissue transglutaminase, the predominant disease associated auto-antigen that regioselectively unmasks the immunogenicity of gluten peptides; and (iii) small molecule agents that selectively inhibit HLA-DQ2 mediated gluten epitope presentation to T-helper cells.
B.Tech., 1985, Indian Institute of Technology, Ph.D., 1990, California Institute of Technology; Postdoctoral, John Innes Centre, U.K., 1990-91;
Dreyfus New Investigator Award, 1991; NSF Young Investigator Award, 1994-99; Packard Fellowship for Science and Engineering, 1994-99; AIChE Allan P. Colburn Award, 1997; ACS Lilly Award in Biological Chemistry, 1999; NSF Alan T. Waterman Award, 1999; ACS Pure Chemistry Award, 2000; Caltech Distinguished Alumni Award, 2000 |
| Remarks： |
Department of Chemical Engineering
Keck Science Building, Room389
723-6538
Email:khosla@stanford.edu
Website:http://www.stanford.edu/dept/chemistry/faculty/khosla/ |
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Promulgator Info |
| Full name: |
administrator |
| Country: |
CN |
| City: |
Dalian |
| Company Name: |
teloon Soft Strategy Co.,LTD |
| Homepage: |
http://www.hqsq.net |
| E-mail: |
reply |
| Phone: |
86-411-82811662 |
| Fax: |
86-411-82819667 |
| Company Address: |
26 Renmin Road ,Dalian China |
| Zip/Postal Code: |
116001 |
| Introduction: |
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