个人简介

Steven Clarke has been on the faculty of the UCLA Department of Chemistry and Biochemistry since 1978. He is currently a Professor of Biochemistry and Director of the UCLA Molecular Biology Institute. He was born in Los Angeles and attended public schools in Altadena and Pasadena, California. He did his undergraduate work at Pomona College in Claremont, majoring in Chemistry and Zoology. During this time, he did undergraduate research at the UCLA Brain Research Institute with Dr. James E. Skinner and Professor Donald Lindsley on neural mechanisms of attention. He was also an NIH fellow in the laboratory of Dr. Peter Mitchell at Glynn Research Laboratories in Bodmin, England studying mitochondrial amino acid transport. He obtained his PhD in Biochemistry and Molecular Biology at Harvard University working as an NSF Fellow with Professor Guido Guidotti on membrane protein-detergent interactions and the identification of the major rat liver mitochondrial polypeptides as enzymes of the urea cycle. He returned to California to do postdoctoral work as a Miller Fellow at the University of California, Berkeley, with Professor Dan Koshland, identifying membrane receptors for bacterial chemotaxis. His research at UCLA has focused on roles of novel protein methyltransferases in aging and biological regulation highlighted by discoveries of the protein L-isoaspartyl repair methyltransferase, the isoprenylcysteine protein methyltransferase, and the protein phosphatase 2A methyltransferase. He has been a visiting scholar at Princeton University (1986-87) and at the University of Washington (2004-2005).

研究领域

Biochemistry/Systems Biology and Biological Regulation/Metabolism/Aging and Development/Chemical Biology

Dr. Clarke has established the paradigm that biological aging is no less than war waged between chemistry and biology. Chemistry represents the spontaneous reactions that degrade biomolecules and biology represents the response of the organism to limit the chemical damage. His laboratory discovered and has characterized a novel pathway that has demonstrated that macromolecular repair is not just for DNA, but for proteins as well! These studies have not only given us a new window to view protein "life" but also suggest that the biological aging process may be closely linked to how well one can keep polypeptides free of spontaneous damage. He has gone on to show that the enzymatic recognition of damage is not limited to DNA and proteins but is a more general response of cells to molecular damage, particularly of crucial metabolites such as cis -aconitate and S -adenosylmethionine. His laboratory has also been in the forefront of identifying new types of methyltransferases that are involved in cellular signaling reactions. His laboratory has discovered enzymes that modify signaling proteins by methylation reactions at C-terminal isoprenylated cysteine residues and leucine residues, as well the first member of the family of protein arginine methyltransferases involved in multiple cellular processes including DNA repair, gene expression, protein translocation, and signaling.

近期论文

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Histidine Methylation of Yeast Ribosomal Protein Rpl3p is Required for Proper 60S Subunit Assembly Al-Hadid,Q., Roy, K., Munroe, W., Dzialo, M.C., Chanfreau, G.F., and Clarke, S.G. (2014) Molecular and Cellular Biology,Aug;34(15):2903-16. Non-Repair Pathways for Minimizing Protein Isoaspartyl Damage in the Yeast Saccharomyces cerevisiae Patananan, A.N., Capri, J., Whitelegge, J.P., and Clarke, S.G. (2014) Journal of Biological Chemistry,Jun 13;289(24):16936-53. A novel small molecule methyltransferase is important for virulence in Candida albican Lissina E, Weiss D, Young B, Rella A, Cheung-Ong K, Del Poeta M, Clarke SG, Giaever G, Nislow C. (2013) ACS Chem Biol. 2013 Dec 20;8(12):2785-93. Mammalian protein arginine methyltransferase 7 (PRMT7) specifically targets RXR sites in lysine-and arginine-rich regions Feng Y, Maity R, Whitelegge JP, Hadjikyriacou A, Li Z, Zurita-Lopez C,Al-Hadid Q, Clark AT, Bedford MT, Masson JY, Clarke SG. (2013) J Biol Chem. 2013 Dec 27;288(52):37010-25. Thermal-Stable Proteins of Fruit of Long-Lived Sacred Lotus Nelumbo nucifera Gaertn var China Antique Shen-Miller, J., Linder, P., Xie, Y., Villa, S., Wooding, K., Clarke, S.G., Loo, R.R.O, and Loo, J.A. (2013) Tropical Plant Biology, 6, 69-84. Brain Proteomics Supports the Role of Glutamate Metabolism and Suggests Other Metabolic Alterations in Protein L-Isoaspartyl Methyltransferase (PIMT)-Knockout Mice Yang,H., Lowenson, J.D., Clarke, S., and Zubarev, R.A. (2013) J. Proteome Research, 12, 4566-4576. An Arabidopsis ATP-Dependent, DEAD-Box RNA Helicase Loses Activity Upon IsoAsp Formation but Is Restored by Protein Isoaspartyl Methyltransferase Nayak, N.R., Putnam, A.A., Addepalli, B., Lowenson, J.D., Chen, T., Jankowsky, E., Perry, S.E., Dinkins, R.D., Limbach, P.A., Clarke, S.G., and Downie, A.B. (2013) Plant Cell, 25, 2573-2586. Circumventing Embryonic Lethality with Lcmt1 Deficiency: Generation of Hypomorphic Lcmt1 Mice with Reduced Protein Phosphatase 2A Methyltransferase Expression and Defects in Insulin Signaling MacKay, K. B., Tu., Y., Young, S. G., and Clarke, S. G. (2013) PLos One, 8,1-11. A Novel Automethylation Reaction in the Aspergillus nidulans LaeA Protein Generates S-Methylmethionine Patananan,A. N., Palmer, J. M., Garvey, G. S., Keller, N. P., and Clarke, S. G. (2013) J. Biol. Chem. 288, 20, 14032-14045. Protein Methylation at the Surface and Buried Deep: Thinking Outside the Histone Box Clarke, S. G. (2013) Trends in Biochemical Sciences, May 2013, 38, 5, 243-252.