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Salih Wakil
Baylor College of MedicineDepartment: Verna and Marrs McClean Biochemistry and Molecular BiologyAddress: One Baylor Plaza BCMC-S319 Houston, Texas 77030 Phone: 713-798-4783 Fax: 713-796-9438 Email: swakil@bcm.tmc.edu Web: intranet.bcm.tmc.edu/departments/biochemistry.html |
Education
B.Sc. Chemistry, American University of Beirut (1948)
Ph.D. Biochemistry, University of Washington at Seattle (1952)
Honors
1967 Paul Lewis Award, American Chemical Society
1968-1969 John Simon Guggenheim Fellowship
1973 Distinguished Duke Alumnus Award
1985 Chilton Award, The University of Texas Health Science Center, Dallas
1988 The Kuwait Prize, Kuwait Foundation for the Advancement of Sciences
1988-1989 President, Association of Medical School Departments of Biochemistry
1990 Election to the National Academy of Sciences
1990 Distinguished Service Award, Arab American Medical Association
1992 Election to Fellowship in the American Academy of Microbiology
1993 Supelco/American Oil Chemists� Society Research Award
2001 The Michael E. DeBakey Excellence in Research Award
2005 6th Annual Bristol-Myers Squibb Freedom to Discover Award for Distinguished Achievement in Metabolic Research
Research Topic
Structure, Function, and Regulation of the Multifunctional Enzymes, Acetyl-CoA Carboxylase and Fatty Acid Synthase
Research Description
Research is centered around the biosynthesis of fatty acids and its regulation. Two unusually large multifunctional enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), are involved in the synthesis of palmitic acid from acetyl-CoA. Current studies in Dr. Wakil's laboratory concern the human enzymes.
Human ACC is present in two isoforms. The cDNAs of both isoforms have been cloned and sequenced and will be expressed in an appropriate expression system in order to study the structure-function relationships of the isoforms. ACC is highly regulated by both allosteric and covalent modifications, many of which are controlled by hormones such as insulin, glucagon, epinephrine, and growth hormones. The 5�-flanking sequences of the two ACC isoforms will be cloned, and using appropriate reporter gene constructs, the effects of these hormones on the expression of the ACC gene will be studied.
The human FAS is another remarkable multifunctional enzyme. The human FAS cDNA has been expressed, and large enough quantities of the active enzyme have been obtained to study its structure-function. Two promoters that regulate FAS expression were identified by utilizing constructs of the 5�-flanking region with luciferase as a reporter gene. The activities of the two promoters and their interaction are under investigation.
Selected Publications
- Abu-Elheiga, L., Oh, W., Kordari, P. and Wakil S.J. (2003). ACC2 mutant mice are protected against obesity and diabetes induced by high fat high carbohydrate diets. Proc. Natl. Acad. Sci. USA. 100: 10207-10212.
- Jianqiang, M., Chirala, S.S. and Wakil, S.J. (2003). Human acetyl-CoA carboxylase 1 gene: Presence of three promoters and heterogeneity at the 5’-untranslated mRNA region. Proc. Natl. Acad. Sci. USA. 100: 7515-7520.
- Al Feel, W., DeMar, J.C. and Wakil, S.J. (2003). A Saccharomyces cerevisiae mutant strain defective in acetyl-CoA carboxylase arrests at the G2/M phase of the cell cycle. Proc. Natl. Acad. Sci. USA. 100: 3095-3100.
- Brink, J., Ludtke S.J., Yang, C., Gu, Z., Wakil, S.J. and Chiu, W. (2002). Quaternary structure of human fatty acid synthase by electron cryomicroscopy. Proc. Natl. Acad. Sci. USA. 99: 138-143.
- Chirala, S.S., Jayakumar, A., Gu, Z. and Wakil, S.J. (2001). Human fatty acid synthase: Role of interdomain in the formation of catalytically active synthase dimer. Proc. Natl. Acad. Sci. USA 98: 3104-3108.
- Abu-Elheiga, L., Matzuk, M.M., Abo-Hashema, K. A. H. and Wakil, S.J. (2001). Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291: 5513: 2613-2616.
- Abu-Elheiga, L., Brinkley, W.R., Zhong, L., Chirala, S.S., Woldegiorgis G., and Wakil, S.J. (2000). The subcellular localization of acetyl-CoA carboxylase 2. Proc. Natl. Acad. Sci. USA 97: 1444-1449.
- Xiong, S., Chirala, S.S., and Wakil, S.J. (2000). Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites. Proc. Natl. Acad. Sci. USA 97: 3948-3953.
- Xiong, S., Chirala, S.S., Hsu, M.H. and Wakil, S.J. (1998). Identification of thyroid hormone response elements in the human fatty acid synthase promoter. Proc. Natl. Acad. Sci. USA 95: 12260-12265.
Lab Members
Lab Photos
Last edited on: August 20, 2009