Biography
Steven Clarke has been on the faculty of the UCLA Department of Chemistry and Biochemistry since 1978. He is currently a Distinguished Professor of Biochemistry and Director of the UCLA Cellular and Molecular Biology Training Program. 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), the University of Washington (2004-2005), and Vanderbilt University (2015).
Publications
A selected list of publications:
Warmack Rebeccah A, Mansilla Eduardo, Goya Rodolfo G, Clarke Steven G Racemized and Isomerized Proteins in Aging Rat Teeth and Eye Lens Rejuvenation research, 2016; 19(4): 309-17.
Jain Kanishk, Warmack Rebeccah A, Debler Erik W, Hadjikyriacou Andrea, Stavropoulos Peter, Clarke Steven G Protein Arginine Methyltransferase Product Specificity is Mediated by Distinct Active-Site Architectures The Journal of biological chemistry, 2016; .
Lowenson Jonathan D, Shmanai Vadim V, Shklyaruck Denis, Clarke Steven G, Shchepinov Mikhail S Deuteration protects asparagine residues against racemization Amino acids, 2016; 19(4): .
Sherkhanov Saken, Korman Tyler P, Clarke Steven G, Bowie James U Production of FAME biodiesel in E. coli by direct methylation with an insect enzyme Scientific reports, 2016; 6(4): 24239.
Al-Hadid Qais, Roy Kevin, Chanfreau Guillaume, Clarke Steven G Methylation of yeast ribosomal protein Rpl3 promotes translational elongation fidelity RNA (New York, N.Y.), 2016; 22(4): 489-98.
Debler Erik W, Jain Kanishk, Warmack Rebeccah A, Feng You, Clarke Steven G, Blobel Günter, Stavropoulos Pete A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase Proceedings of the National Academy of Sciences of the United States of America, 2016; 113(8): 2068-73.
Al-Hadid Qais, White Jonelle, Clarke Steven Ribosomal protein methyltransferases in the yeast Saccharomyces cerevisiae: Roles in ribosome biogenesis and translation Biochemical and biophysical research communications, 2016; 470(3): 552-7.
Fu Xudong, Chin Randall M, Vergnes Laurent, Hwang Heejun, Deng Gang, Xing Yanpeng, Pai Melody Y, Li Sichen, Ta Lisa, Fazlollahi Farbod, Chen Chuo, Prins Robert M, Teitell Michael A, Nathanson David A, Lai Albert, Faull Kym F, Jiang Meisheng, Clarke Steven G, Cloughesy Timothy F, Graeber Thomas G, Braas Daniel, Christofk Heather R, Jung Michael E, Reue Karen, Huang Jing 2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling Cell metabolism, 2015; 22(3): 508-15.
Yang Yanzhong, Hadjikyriacou Andrea, Xia Zheng, Gayatri Sitaram, Kim Daehoon, Zurita-Lopez Cecilia, Kelly Ryan, Guo Ailan, Li Wei, Clarke Steven G, Bedford Mark T PRMT9 is a type II methyltransferase that methylates the splicing factor SAP145 Nature communications, 2015; 6(27): 6428.
Hadjikyriacou Andrea, Yang Yanzhong, Espejo Alexsandra, Bedford Mark T, Clarke Steven G Unique Features of Human Protein Arginine Methyltransferase 9 (PRMT9) and Its Substrate RNA Splicing Factor SF3B2 The Journal of biological chemistry, 2015; 290(27): 16723-43.
Patananan Alexander N, Budenholzer Lauren M, Pedraza Maria E, Torres Eric R, Adler Lital N, Clarke Steven G The invertebrate Caenorhabditis elegans biosynthesizes ascorbate Archives of biochemistry and biophysics, 2015; 569(27): 32-44.
Patananan Alexander Nikolich, Budenholzer Lauren Michelle, Eskin Ascia, Torres Eric Rommel, Clarke Steven Gerard Ethanol-induced differential gene expression and acetyl-CoA metabolism in a longevity model of the nematode Caenorhabditis elegans Experimental gerontology, 2015; 61(27): 20-30.
Dzialo Maria C, Travaglini Kyle J, Shen Sean, Loo Joseph A, Clarke Steven G A new type of protein lysine methyltransferase trimethylates Lys-79 of elongation factor 1A Biochemical and biophysical research communications, 2014; 455(3-4): 382-9.
Feng You, Hadjikyriacou Andrea, Clarke Steven G Substrate specificity of human protein arginine methyltransferase 7 (PRMT7): the importance of acidic residues in the double E loop The Journal of biological chemistry, 2014; 289(47): 32604-16.
Dzialo Maria C, Travaglini Kyle J, Shen Sean, Roy Kevin, Chanfreau Guillaume F, Loo Joseph A, Clarke Steven G Translational roles of elongation factor 2 protein lysine methylation The Journal of biological chemistry, 2014; 289(44): 30511-24.
Al-Hadid Qais, Roy Kevin, Munroe William, Dzialo Maria C, Chanfreau Guillaume F, Clarke Steven G Histidine methylation of yeast ribosomal protein Rpl3p is required for proper 60S subunit assembly Molecular and cellular biology, 2014; 34(15): 2903-16.
Patananan Alexander N, Capri Joseph, Whitelegge Julian P, Clarke Steven G Non-repair pathways for minimizing protein isoaspartyl damage in the yeast Saccharomyces cerevisiae The Journal of biological chemistry, 2014; 289(24): 16936-53.
Lissina Elena, Weiss David, Young Brian, Rella Antonella, Cheung-Ong Kahlin, Del Poeta Maurizio, Clarke Steven G, Giaever Guri, Nislow Corey A novel small molecule methyltransferase is important for virulence in Candida albicans ACS chemical biology, 2013; 8(12): 2785-93.
Feng You, Maity Ranjan, Whitelegge Julian P, Hadjikyriacou Andrea, Li Ziwei, Zurita-Lopez Cecilia, Al-Hadid Qais, Clark Amander T, Bedford Mark T, Masson Jean-Yves, Clarke Steven G Mammalian protein arginine methyltransferase 7 (PRMT7) specifically targets RXR sites in lysine- and arginine-rich regions The Journal of biological chemistry, 2013; 288(52): 37010-25.
Yang Hongqian, Lowenson Jonathan D, Clarke Steven, Zubarev Roman A Brain proteomics supports the role of glutamate metabolism and suggests other metabolic alterations in protein l-isoaspartyl methyltransferase (PIMT)-knockout mice Journal of proteome research, 2013; 12(10): 4566-76.
Shen-Miller J, Lindner Petra, Xie Yongming, Villa Sarah, Wooding Kerry, Clarke Steven G, Loo Rachel R O, Loo Joseph A Thermal-stable proteins of fruit of long-living Sacred Lotus Nelumbo nucifera Gaertn var. China Antique Tropical plant biology, 2013; 6(2-3): .
Nayak Nihar R, Putnam Andrea A, Addepalli Balasubrahmanyam, Lowenson Jonathan D, Chen Tingsu, Jankowsky Eckhard, Perry Sharyn E, Dinkins Randy D, Limbach Patrick A, Clarke Steven G, Downie A Bruce An Arabidopsis ATP-dependent, DEAD-box RNA helicase loses activity upon IsoAsp formation but is restored by PROTEIN ISOASPARTYL METHYLTRANSFERASE The Plant cell, 2013; 25(7): 2573-86.
Mackay Kennen B, Tu Yiping, Young Stephen G, Clarke Steven G Circumventing Embryonic Lethality with Lcmt1 Deficiency: Generation of Hypomorphic Lcmt1 Mice with Reduced Protein Phosphatase 2A Methyltransferase Expression and Defects in Insulin Signaling PloS one, 2013; 8(6): e65967.
Patananan Alexander N, Palmer Jonathan M, Garvey Graeme S, Keller Nancy P, Clarke Steven G A novel automethylation reaction in the Aspergillus nidulans LaeA protein generates S-methylmethionine The Journal of biological chemistry, 2013; 288(20): 14032-45.
Clarke Steven G Protein methylation at the surface and buried deep: thinking outside the histone box Trends in biochemical sciences, 2013; 38(5): 243-52.
Dai Shujia, Ni Wenqin, Patananan Alexander N, Clarke Steven G, Karger Barry L, Zhou Zhaohui Sunny Integrated proteomic analysis of major isoaspartyl-containing proteins in the urine of wild type and protein L-isoaspartate O-methyltransferase-deficient mice Analytical chemistry, 2013; 85(4): 2423-30.
Dhar Surbhi, Vemulapalli Vidyasiri, Patananan Alexander N, Huang Grace L, Di Lorenzo Alessandra, Richard Stephane, Comb Michael J, Guo Ailan, Clarke Steven G, Bedford Mark T Loss of the major Type I arginine methyltransferase PRMT1 causes substrate scavenging by other PRMTs Scientific reports, 2013; 3(1): 1311.
Yang Mei-Ling, Gee Alaric J P, Gee Renelle J, Zurita-Lopez Cecilia I, Khare Shilpi, Clarke Steven G, Mamula Mark J Lupus autoimmunity altered by cellular methylation metabolism Autoimmunity, 2013; 46(1): 21-31.
Young Brian D, Weiss David I, Zurita-Lopez Cecilia I, Webb Kristofor J, Clarke Steven G, McBride Anne E Identification of methylated proteins in the yeast small ribosomal subunit: a role for SPOUT methyltransferases in protein arginine methylation Biochemistry, 2012; 51(25): 5091-104.
Castro Paola V, Khare Shilpi, Young Brian D, Clarke Steven G Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae PloS one, 2012; 7(1): e29984.
Zurita-Lopez Cecilia I, Sandberg Troy, Kelly Ryan, Clarke Steven G Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming Ï-NG-monomethylated arginine residues The Journal of biological chemistry, 2012; 287(11): 7859-70.
MacKay Kennen B, Lowenson Jonathan D, Clarke Steven G Wortmannin reduces insulin signaling and death in seizure-prone Pcmt1-/- mice PloS one, 2012; 7(10): e46719.
Adler Lital N, Gomez Tara A, Clarke Steven G, Linster Carole L A novel GDP-D-glucose phosphorylase involved in quality control of the nucleoside diphosphate sugar pool in Caenorhabditis elegans and mammals The Journal of biological chemistry, 2011; 286(24): 21511-23.
Webb Kristofor J, Al-Hadid Qais, Zurita-Lopez Cecilia I, Young Brian D, Lipson Rebecca S, Clarke Steven G The ribosomal l1 protuberance in yeast is methylated on a lysine residue catalyzed by a seven-beta-strand methyltransferase The Journal of biological chemistry, 2011; 286(21): 18405-13.
Khare Shilpi, Linster Carole L, Clarke Steven G The interplay between protein L-isoaspartyl methyltransferase activity and insulin-like signaling to extend lifespan in Caenorhabditis elegans PloS one, 2011; 6(6): e20850.
Petrossian Tanya C, Clarke Steven G Uncovering the human methyltransferasome Molecular & cellular proteomics : MCP, 2011; 10(1): M110.000976.
Webb Kristofor J, Zurita-Lopez Cecilia I, Al-Hadid Qais, Laganowsky Arthur, Young Brian D, Lipson Rebecca S, Souda Puneet, Faull Kym F, Whitelegge Julian P, Clarke Steven G A novel 3-methylhistidine modification of yeast ribosomal protein Rpl3 is dependent upon the YIL110W methyltransferase The Journal of biological chemistry, 2010; 285(48): 37598-606.
Lipson Rebecca S, Webb Kristofor J, Clarke Steven G Two novel methyltransferases acting upon eukaryotic elongation factor 1A in Saccharomyces cerevisiae Archives of biochemistry and biophysics, 2010; 500(2): 137-43.
Vinci Chris R, Clarke Steven G Homocysteine methyltransferases Mht1 and Sam4 prevent the accumulation of age-damaged (R,S)-AdoMet in the yeast Saccharomyces cerevisiae The Journal of biological chemistry, 2010; 285(27): 20526-31.
Webb Kristofor J, Lipson Rebecca S, Al-Hadid Qais, Whitelegge Julian P, Clarke Steven G Identification of protein N-terminal methyltransferases in yeast and humans Biochemistry, 2010; 49(25): 5225-35.
Fisk John C, Zurita-Lopez Cecilia, Sayegh Joyce, Tomasello Danielle L, Clarke Steven G, Read Laurie K TbPRMT6 is a type I protein arginine methyltransferase that contributes to cytokinesis in Trypanosoma brucei Eukaryotic cell, 2010; 9(6): 866-77.
Vinci Chris R, Clarke Steven G Yeast, plants, worms, and flies use a methyltransferase to metabolize age-damaged (R,S)-AdoMet, but what do mammals do? Rejuvenation research, 2010; 13(2-3): 362-4.
Petrossian Tanya, Clarke Steven Bioinformatic Identification of Novel Methyltransferases Epigenomics, 2009; 1(1): 163-175.
Khare Shilpi, Gomez Tara, Linster Carole L, Clarke Steven G Defective responses to oxidative stress in protein l-isoaspartyl repair-deficient Caenorhabditis elegans Mechanisms of ageing and development, 2009; 130(10): 670-80.
Lakowski Ted M, Zurita-Lopez Cecilia, Clarke Steven G, Frankel Adam Approaches to measuring the activities of protein arginine N-methyltransferases Analytical biochemistry, 2009; .
Petrossian, T. C., and Clarke, S. G. Bioinformatic Identification of Novel Methyltransferases Epigenomics, 2009; 1: 163-175.
Fisk John C, Sayegh Joyce, Zurita-Lopez Cecilia, Menon Sarita, Presnyak Vladimir, Clarke Steven G, Read Laurie K A type III protein arginine methyltransferase from the protozoan parasite Trypanosoma brucei The Journal of biological chemistry, 2009; 284(17): 11590-600.
Petrossian Laurie K, Clarke Laurie K Multiple motif scanning to identify methyltransferases from the yeast proteome Molecular & cellular proteomics : MCP, 2009; 284(17): .
Bedford Mark T, Clarke Steven G Protein arginine methylation in mammals: who, what, and why Molecular cell, 2009; 33(1): 1-13.
Gomez Tara A, Banfield Kelley L, Clarke Steven G The protein L-isoaspartyl-O-methyltransferase functions in the Caenorhabditis elegans stress response Mechanisms of ageing and development, 2008; 129(12): 752-8.
Linster Carole L, Clarke Steven G L-Ascorbate biosynthesis in higher plants: the role of VTC2 Trends in plant science, 2008; 13(11): 567-73.
Sayegh Joyce, Clarke Steven G Hsl7 is a substrate-specific type II protein arginine methyltransferase in yeast Biochem. Biophys. Res. Commun, 2008; 372(4): 811-5.
Banfield Kelley L, Gomez Tara A, Lee Wendy, Clarke Steven, Larsen Pamela L Protein-repair and hormone-signaling pathways specify dauer and adult longevity and dauer development in Caenorhabditis elegans The journals of gerontology. Series A, Biological sciences and medical sciences, 2008; 63(8): 798-808.
Dumlao Darren S, Hertz Nicholas, Clarke Steven Secreted 3-isopropylmalate methyl ester signals invasive growth during amino acid starvation in Saccharomyces cerevisiae Biochemistry, 2008; 47(2): 698-709.
Sayegh Joyce, Webb Kristofor, Cheng Donghang, Bedford Mark T, Clarke Steven G Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain J. Biol. Chem, 2007; 282(50): 36444-53.
Gomez Tara A, Clarke Steven G Autophagy and insulin/TOR signaling in Caenorhabditis elegans pcm-1 protein repair mutants Autophagy, 2007; 3(4): 357-9.
Linster Carole L, Gomez Tara A, Christensen Kathryn C, Adler Lital N, Young Brian D, Brenner Charles, Clarke Steven G Arabidopsis VTC2 encodes a GDP-L-galactose phosphorylase, the last unknown enzyme in the Smirnoff-Wheeler pathway to ascorbic acid in plants J. Biol. Chem, 2007; 282(26): 18879-85.
Vinci Chris R, Clarke Steven G Recognition of age-damaged (R,S)-adenosyl-L-methionine by two methyltransferases in the yeast Saccharomyces cerevisiae J. Biol. Chem, 2007; 282(12): 8604-12.
Gomez Tara A, Banfield Kelley L, Trogler Dorothy M, Clarke Steven G The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity and autophagy Developmental biology, 2007; 303(2): 493-500.
Villa Sarah T, Xu Qilong, Downie A Bruce, Clarke Steven G Arabidopsis Protein Repair L-Isoaspartyl Methyltransferases: Predominant Activities at Lethal Temperatures Physiologia plantarum, 2006; 128(4): 581-592.
Clarke Steven G 16 Inhibition of mammalian protein methyltransferases by 5′-methylthioadenosine (MTA): A mechanism of action of dietary same? The Enzymes, 2006; 24(2): 467-93.
Farrar Christine E, Huang Christine S, Clarke Steven G, Houser Carolyn R Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice The Journal of comparative neurology, 2005; 493(4): 524-37.
Porras-Yakushi Tanya R, Whitelegge Julian P, Miranda Tina Branscombe, Clarke Steven A novel SET domain methyltransferase modifies ribosomal protein Rpl23ab in yeast The Journal of biological chemistry, 2005; 280(41): 34590-8.
Lee Jaeho, Sayegh Joyce, Daniel Jeremy, Clarke Steven, Bedford Mark T PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family The Journal of biological chemistry, 2005; 280(38): 32890-6.
Farrar Christine, Houser Carolyn R, Clarke Steven Activation of the PI3K/Akt signal transduction pathway and increased levels of insulin receptor in protein repair-deficient mice Aging cell, 2005; 4(1): 1-12.
Miranda Tina Branscombe, Miranda Mark, Frankel Adam, Clarke Steven PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity The Journal of biological chemistry, 2004; 279(22): 22902-7.
Clarke Steven Aging as war between chemical and biochemical processes: protein methylation and the recognition of age-damaged proteins for repair Ageing research reviews, 2003; 2(3): 263-85.
Young Stephen G, Clarke Steven G, Bergoc Martin O, Phillips Mark, Fong Loren G 10 Genetic approaches to understanding the physiologic importance of the carboxyl methylation of isoprenylated proteins The Enzymes, 2006; 24(3): 273-301.
Stetler April, Winograd Claudia, Sayegh Joyce, Cheever Anne, Patton Erin, Zhang Xing, Clarke Steven, Ceman Stephanie Identification and characterization of the methyl arginines in the fragile X mental retardation protein Fmrp Human molecular genetics, 2006; 15(1): 87-96.
Linster Carole L, Adler Lital N, Webb Kristofor, Christensen Kathryn C, Brenner Charles, Clarke Steven G A second GDP-L-galactose phosphorylase in arabidopsis en route to vitamin C. Covalent intermediate and substrate requirements for the conserved reaction The Journal of biological chemistry, 2008; 283(27): 18483-92.
Hadjikyriacou Andrea, Clarke Steven G Caenorhabditis elegans PRMT-7 and PRMT-9 Are Evolutionarily Conserved Protein Arginine Methyltransferases with Distinct Substrate Specificities Biochemistry, 2017; 56(20): 2612-2626.
Miranda Tina Branscombe, Webb Kristofor J, Edberg Dale D, Reeves Raymond, Clarke Steven Protein arginine methyltransferase 6 specifically methylates the nonhistone chromatin protein HMGA1a Biochemical and biophysical research communications, 2005; 336(3): 831-5.
Alfaro Joshua F, Gillies Laura A, Sun He G, Dai Shujia, Zang Tianzhu, Klaene Joshua J, Kim Byung Ju, Lowenson Jonathan D, Clarke Steven G, Karger Barry L, Zhou Zhaohui Sunny Chemo-enzymatic detection of protein isoaspartate using protein isoaspartate methyltransferase and hydrazine trapping Analytical chemistry, 2008; 80(10): 3882-9.
Lipson Rebecca S, Clarke Steven G S-adenosylmethionine-dependent protein methylation in mammalian cytosol via tyrphostin modification by catechol-O-methyltransferase The Journal of biological chemistry, 2007; 282(42): 31094-102.
Kafková Lucie, Debler Erik W, Fisk John C, Jain Kanishk, Clarke Steven G, Read Laurie K The Major Protein Arginine Methyltransferase in Trypanosoma brucei Functions as an Enzyme-Prozyme Complex The Journal of biological chemistry, 2017; 292(6): 2089-2100.
Pasternack Deborah A, Sayegh Joyce, Clarke Steven, Read Laurie K Evolutionarily divergent type II protein arginine methyltransferase in Trypanosoma brucei Eukaryotic cell, 2007; 6(9): 1665-81.
Caslavka Zempel Katelyn E, Vashisht Ajay A, Barshop William D, Wohlschlegel James A, Clarke Steven G Determining the Mitochondrial Methyl Proteome in Saccharomyces cerevisiae using Heavy Methyl SILAC Journal of proteome research, 2016; 15(12): 4436-4451.
Clarke Steven Gerard HIV protease inhibitors and nuclear lamin processing: getting the right bells and whistles Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(35): 13857-8.
Zou Yan, Webb Kristofor, Perna Avi D, Zhang Qingchun, Clarke Steven, Wang Yinsheng A mass spectrometric study on the in vitro methylation of HMGA1a and HMGA1b proteins by PRMTs: methylation specificity, the effect of binding to AT-rich duplex DNA, and the effect of C-terminal phosphorylation Biochemistry, 2007; 46(26): 7896-906.
Urzica Eugen I, Casero David, Yamasaki Hiroaki, Hsieh Scott I, Adler Lital N, Karpowicz Steven J, Blaby-Haas Crysten E, Clarke Steven G, Loo Joseph A, Pellegrini Matteo, Merchant Sabeeha S Systems and trans-system level analysis identifies conserved iron deficiency responses in the plant lineage The Plant cell, 2012; 24(10): 3921-48.
McBride Anne E, Zurita-Lopez Cecilia, Regis Anthony, Blum Emily, Conboy Ana, Elf Shannon, Clarke Steven Protein arginine methylation in Candida albicans: role in nuclear transport Eukaryotic cell, 2007; 6(7): 1119-29.
Urzica Eugen I, Adler Lital N, Page M Dudley, Linster Carole L, Arbing Mark A, Casero David, Pellegrini Matteo, Merchant Sabeeha S, Clarke Steven G Impact of oxidative stress on ascorbate biosynthesis in Chlamydomonas via regulation of the VTC2 gene encoding a GDP-L-galactose phosphorylase The Journal of biological chemistry, 2012; 287(17): 14234-45.
Lissina Elena, Young Brian, Urbanus Malene L, Guan Xue Li, Lowenson Jonathan, Hoon Shawn, Baryshnikova Anastasia, Riezman Isabelle, Michaut Magali, Riezman Howard, Cowen Leah E, Wenk Markus R, Clarke Steven G, Giaever Guri, Nislow Corey A systems biology approach reveals the role of a novel methyltransferase in response to chemical stress and lipid homeostasis PLoS genetics, 2011; 7(10): e1002332.
Porras-Yakushi Tanya R, Whitelegge Julian P, Clarke Steven Yeast ribosomal/cytochrome c SET domain methyltransferase subfamily: identification of Rpl23ab methylation sites and recognition motifs The Journal of biological chemistry, 2007; 282(17): 12368-76.
Rust Heather L, Zurita-Lopez Cecilia I, Clarke Steven, Thompson Paul R Mechanistic studies on transcriptional coactivator protein arginine methyltransferase 1 Biochemistry, 2011; 50(16): 3332-45.
Butler Jill S, Zurita-Lopez Cecilia I, Clarke Steven G, Bedford Mark T, Dent Sharon Y R Protein-arginine methyltransferase 1 (PRMT1) methylates Ash2L, a shared component of mammalian histone H3K4 methyltransferase complexes The Journal of biological chemistry, 2011; 286(14): 12234-44.
Vigneswara Vasanthy, Lowenson Jonathan D, Powell Claire D, Thakur Matthew, Bailey Kevin, Clarke Steven, Ray David E, Carter Wayne G Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme The Journal of biological chemistry, 2006; 281(43): 32619-29.
Porras-Yakushi Tanya R, Whitelegge Julian P, Clarke Steven A novel SET domain methyltransferase in yeast: Rkm2-dependent trimethylation of ribosomal protein L12ab at lysine 10 The Journal of biological chemistry, 2006; 281(47): 35835-45.
Chen Tingsu, Nayak Nihar, Majee Susmita Maitra, Lowenson Jonathan, Schäfermeyer Kim R, Eliopoulos Alyssa C, Lloyd Taylor D, Dinkins Randy, Perry Sharyn E, Forsthoefel Nancy R, Clarke Steven G, Vernon Daniel M, Zhou Zhaohui Sunny, Rejtar Tomas, Downie A Bruce Substrates of the Arabidopsis thaliana protein isoaspartyl methyltransferase 1 identified using phage display and biopanning The Journal of biological chemistry, 2010; 285(48): 37281-92.
Yang Mei-Ling, Doyle Hester A, Gee Renelle J, Lowenson Jonathan D, Clarke Steven, Lawson Brian R, Aswad Dana W, Mamula Mark J Intracellular protein modification associated with altered T cell functions in autoimmunity Journal of immunology (Baltimore, Md. : 1950), 2006; 177(7): 4541-9.
Lipson Rebecca S, Webb Kristofor J, Clarke Steven G Rmt1 catalyzes zinc-finger independent arginine methylation of ribosomal protein Rps2 in Saccharomyces cerevisiae Biochemical and biophysical research communications, 2010; 391(4): 1658-62.
Webb Kristofor J, Laganowsky Arthur, Whitelegge Julian P, Clarke Steven G Identification of two SET domain proteins required for methylation of lysine residues in yeast ribosomal protein Rpl42ab The Journal of biological chemistry, 2008; 283(51): 35561-8.
Miranda Tina Branscombe, Sayegh Joyce, Frankel Adam, Katz Jonathan E, Miranda Mark, Clarke Steven Yeast Hsl7 (histone synthetic lethal 7) catalyses the in vitro formation of omega-N(G)-monomethylarginine in calf thymus histone H2A The Biochemical journal, 2006; 395(3): 563-70.
Biography
Professor Koehler has been a faculty member in the Department of Chemistry and Biochemistry since 1999. She came to UCLA after doing post-doctoral research in the laboratory of Dr Gottfried Schatz at the Biozentrum, Basel, Switzerland. Her research characterized a new protein import pathway in the mitochondrion and linked a defect in protein import with the inherited disease deafness-dystonia syndrome. Dr. Koehler completed her graduate studies at Iowa State University, characterizing the inheritance of mitochondrial DNA during her M.S. studies and studying dimorphism in Saccharomyces cerevisiae . Dr. Koehler is a former Damon Runyon Scholar and current Established Investigator of the American Heart Association. Dr. Koehler is an Associate Editor for Current Genetics . She has been a member of the Molecular Biology Institute, Jonsson Cancer Center, and the Brain Research Institute since 1999. Her current research focuses on developing vertebrate models for mitochondrial diseases as well as using yeast for mechanistic studies on mitochondrial biogenesis.
Publications
A selected list of publications:
Dabir Deepa V, Hasson Samuel A, Setoguchi Kiyoko, Johnson Meghan E, Wongkongkathep Piriya, Douglas Colin J, Zimmerman Johannes, Damoiseaux Robert, Teitell Michael A, Koehler Carla M A small molecule inhibitor of redox-regulated protein translocation into mitochondria Developmental cell, 2013; 25(1): 81-92.
Arango Nelson Alexander, Li Li, Dabir Deepa, Nicolau Fotini, Pieretti-Vanmarcke Rafael, Koehler Carla, McCarrey John R, Lu Naifang, Donahoe Patricia K Meiosis I arrest abnormalities lead to severe oligozoospermia in meiosis 1 arresting protein (M1ap)-deficient mice Biology of reproduction, 2013; 88(3): 76.
Zhang Jin, Nuebel Esther, Daley George Q, Koehler Carla M, Teitell Michael A Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal Cell stem cell, 2012; 11(5): 589-95.
Bourens Myriam, Dabir Deepa V, Tienson Heather L, Sorokina Irina, Koehler Carla M, Barrientos Antoni Role of twin Cys-Xaa9-Cys motif cysteines in mitochondrial import of the cytochrome C oxidase biogenesis factor Cmc1 The Journal of biological chemistry, 2012; 287(37): 31258-69.
Claypool Steven M, Koehler Carla M The complexity of cardiolipin in health and disease Trends in biochemical sciences, 2012; 37(1): 32-41.
Claypool Steven M, Whited Kevin, Srijumnong Santi, Han Xianlin, Koehler Carla M Barth syndrome mutations that cause tafazzin complex lability The Journal of cell biology, 2011; 192(3): 447-62.
Curado Silvia, Ober Elke A, Walsh Susan, Cortes-Hernandez Paulina, Verkade Heather, Koehler Carla M, Stainier Didier Y R The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model Disease models & mechanisms, 2010; 3(7-8): 486-95.
Zaltsman Yehudit, Shachnai Liat, Yivgi-Ohana Natalie, Schwarz Michal, Maryanovich Maria, Houtkooper Riekelt H, Vaz Frédéric Maxime, De Leonardis Francesco, Fiermonte Giuseppe, Palmieri Ferdinando, Gillissen Bernhard, Daniel Peter T, Jimenez Erin, Walsh Susan, Koehler Carla M, Roy Soumya Sinha, Walter Ludivine, Hajnóczky György, Gross Atan MTCH2/MIMP is a major facilitator of tBID recruitment to mitochondria Nature cell biology, 2010; 12(6): 553-62.
Hasson Samuel A, Damoiseaux Robert, Glavin Jenny D, Dabir Deepa V, Walker Scott S, Koehler Carla M Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocation Proceedings of the National Academy of Sciences of the United States of America, 2010; 107(21): 9578-83.
Tienson Heather L, Dabir Deepa V, Neal Sonya E, Loo Rachel, Hasson Samuel A, Boontheung Pinmanee, Kim Sung-Kun, Loo Joseph A, Koehler Carla M Reconstitution of the mia40-erv1 oxidative folding pathway for the small tim proteins Molecular biology of the cell, 2009; 20(15): 3481-90.
Lu, G., H. Sun, P. Korge, C. M. Koehler, J. N. Weiss, and Y. Wang Functional characterization of a mitochondrial Ser/Thr protein phosphatase in cell death regulation Methods Enzymol, 2009; 457: 255-273.
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Chacinska A., C. M. Koehler, D. Milenkovic, T. Lithgow, and N. Pfanner Importing mitochondrial proteins: machineries and mechanisms Cell, 2009; 138: 628-644.
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Tienson, H. L., D. V. Dabir, S. E. Neal, R. Loo, S. A. Hasson, P. Boontheung, S.-K. Kim, J. A. Loo, and C. M. Koehler Reconstitution of the Mia40-Erv1 oxidative folding pathway for the small Tim proteins Mol. Biol. Cell, 2009; 20: 3481-3490.
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Koehler, C. M. and H. L. Tienson Redox regulation of protein folding in the mitochondrial intermembrane space Biochim Biophys Acta, 2009; 1793: 139-145.
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Koehler Carla M, Tienson Heather L Redox regulation of protein folding in the mitochondrial intermembrane space Biochimica et biophysica acta, 2009; 1793(1): 139-45.
Claypool Steven M, Boontheung Pinmanee, McCaffery J Michael, Loo Joseph A, Koehler Carla M The cardiolipin transacylase, tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome Molecular biology of the cell, 2008; 19(12): 5143-55.
Beverly Kristen N, Sawaya Michael R, Schmid Einhard, Koehler Carla M The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23 Journal of molecular biology, 2008; 382(5): 1144-56.
Claypool Steven M, Oktay Yavuz, Boontheung Pinmanee, Loo Joseph A, Koehler Carla M Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane The Journal of cell biology, 2008; 182(5): 937-50.
Walsh Susan, Koehler Carla M Gazing at translocation in the mitochondrion Cell, 2008; 134(3): 382-3.
Gebert, N., A. Chacinska, K. Wagner, B. Guiard, C. M. Koehler, P. Rehling, N. Pfanner, and N. Wiedemann Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase EMBO Rep, 2008; 9: 548-554.
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Claypool, S. M., Y. Oktay, P. Boontheung, J. A. Loo, and C. M. Koehler Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane J. Cell Biol, 2008; 182: 937-950.
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Walsh, S. and C. M. Koehler Gazing at translocation in the mitochondrion Cell, 2008; 134: 382-383.
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Beverly, K. N., M, R. Sawaya, E. Schmid, and C. M. Koehler The Tim8-Tim13 complex has multiple substrate binding sites and binds cooperatively to Tim23 J. Mol. Biol, 2008; 382: 1144-1156.
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Claypool, S. M., P. Boontheung, J. M. McCaffery, J. A. Loo, and C. M. Koehler The cardiolipin transacylase, Tafazzin, associates with two distinct respiratory components providing insight into Barth syndrome Mol. Biol. Cell, 2008; 19: 5143-5155.
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Dabir Deepa V, Leverich Edward P, Kim Sung-Kun, Tsai Frederick D, Hirasawa Masakazu, Knaff David B, Koehler Carla M A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1 The EMBO journal, 2007; 26(23): 4801-11.
Hwang David K, Claypool Steven M, Leuenberger Danielle, Tienson Heather L, Koehler Carla M Tim54p connects inner membrane assembly and proteolytic pathways in the mitochondrion The Journal of cell biology, 2007; 178(7): 1161-75.
Lu G., Ren S., Korge P., Choi J., Dong Y., Weiss J., Koehler C., Chen J.N., Wang Y. A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development Genes Dev, 2007; 21: 784-796.
Dabir, D. V., E. P. Leverich, S.-K. Kim, F. D. Tsai, M. Hirasawa, D. B. Knaff, and C. M. Koehler A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1, EMBO J, 2007; 26: 4801-4811.
Sediva, A., C. I. E. Smith, A. C. Asplund, J. Hadac, A. Janda, J. Zeman, H. Hansikova; L. Dvorakova, L. Mrazova, S. Velbri, C. Koehler, K. Roesch, K. E. Sullivan, T. Futatani, H. Ochs Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L and DRP2 genes, J. Clin. Immunol. , 2007; 27: 640-646.
Chen, H.-W., C. M. Koehler, and M. A. Teitell Human polynucleotide phosphorylase: Location matters, Trends Cell Biol, 2007; 17: 600-608.
Stuart, R.A. and C.M. Koehler In Vitro Analysis of Yeast Mitochondrial Protein Import, In Morgan, K. (ed.) Current Protocols in Cell Biology, 2007; 11.19.1-11.19.20.
French S.W., Dawson D.W., Chen H.W., Rainey R.N., Sievers S.A., Balatoni C.E., Wong L., Troke J.J., Nguyen M.T., Koehler C.M., Teitell M.A. The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity Cancer Letts, 2007; 248: 198-210.
Oktay, Y., R.N.Rainey, and C.M. Koehler The function of TIM22 in the insertion of inner membrane proteins in mitochondria, Dalbey, R.E., Koehler, C.M., and Tamanoi, F. (eds.) The Enzymes: Molecular Machines Involved in Protein Transport across Membrane, 2007; 25: 367-386.
Hwang, D. K., S. M. Claypool, H. D. Tienson, D. Leuenberger, C. M. Koehler Tim54p mediates assembly of the i-AAA protease Yme1p, J. Cell Biol. , 2007; 178: 1161-75.
Claypool Steven M, McCaffery J Michael, Koehler Carla M Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins The Journal of cell biology, 2006; 174(3): 379-90.
Rainey R.N., Glavin J.D., Chen H.W., French S.W., Teitell M.A., Koehler C.M. A new function in translocation for the mitochondrial i-AAA protease Yme1: import of polynucleotide phosphorylase into the intermembrane space Mol. Cell. Biol, 2006; 26(22): 8488-8497.
Chen, H.W., Rainey, R.N., Balatoni C.E., Dawson D.W., Troke J.J., Wasiak S., Hong J.S., McBride H.M., Koehler C.M., Teitell M.A., French S.W. Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis Mol. Cell. Biol, 2006; 26(22): 8475-8487.
Claypool, S.M., McCaffery, J.M., Koehler, C.M. Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins, J. Cell Biol, 2006; 184: 379-390.
Koehler, C.M., Beverly, K.N., Leverich, E.P. Redox Pathways of the Mitochondrion, Antioxid. Redox. Signal, 2006; 8: 813-822.
Claypool SM, Koehler CM Hereditary spastic paraplegia: respiratory choke or unactivated substrate? Cell. , 2005; 123(2): 183-5.
Claypool Steven M, Koehler Carla M Hereditary spastic paraplegia: respiratory choke or unactivated substrate? Cell, 2005; 123(2): 183-5.
Likic VA, Perry A, Hulett J,Derby M, Traven A, Waller RF, Keeling PJ, Koehler CM, Curran SP, Gooley PR and Lithgow T Patterns that define the four domains conserved in known and novel isoforms of the protein import receptor Tom20 J. Mol. Biol, 2005; 347: 81-93.
Koehler CM, Hwang DK Protein translocation across membranes, Encyclopedia of Molecular Cell Biology and Molecular Medicine, 2005; 11: 287-308.
Curran SP, Leverich EP, Koehler CM, Larsen PL Defective mitochondrial protein translocation precludes normal Caenorhabditis elegans development The Journal of biological chemistry. , 2004; 279(52): 54655-62.
Curran SP, Leuenberger D, Leverich EP, Hwang DK, Beverly KN, Koehler CM The role of Hot13p and redox chemistry in the mitochondrial TIM22 import pathway The Journal of biological chemistry. , 2004; 279(42): 43744-51.
Curran SP and Koehler CM Mitochondrial biogenesis. Protein import into and across the inner membrane, Topics in Current Genetics: Mitochondrial Function and Biogenesis, 2004; 8: 59-80.
Koehler CM New developments in mitochondrial assembly Annual review of cell and developmental biology. , 2004; 20: 309-35.
Leuenberger D, Curran SP and Koehler CM Structure, bioenergetics, and biogenesis of mitochondria, The Biogenesis of Cellular Organelles, 2004; 138-163.
Roesch K, Hynds PH, Varga R, Tranebjaerg L and Koehler CM The calcium-binding apartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex Hum. Mol. Gen, 2004; 13: 2101-2111.
Koehler CM The small Tim proteins and the twin Cx3C motif Trends in biochemical sciences. , 2004; 29(1): 1-4.
Koehler CM Import and assembly, Genetics of Mitochondrial Diseases, 2003; 47-68.
Dyall SD, Lester DC, Schneider RE, Delgadillo-Correa MG, Plumper E, Martinez A, Koehler CM, Johnson PJ Trichomonas vaginalis Hmp35, a putative pore-forming hydrogenosomal membrane protein, can form a complex in yeast mitochondria J. Biol. Chem, 2003; 278: 30548-30461.
van der Bliek AM, Koehler CM A mitochondrial rhomboid protease Developmental cell. , 2003; 4(6): 769-70.
Leuenberger D, Curran SP, Wong D, Koehler CM The role of Tim9p in the assembly of the TIM22 import complexes Traffic (Copenhagen, Denmark) , 2003; 4(3): 144-52.
Curran SP, Leuenberger D, Schmidt E, Koehler CM The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins The Journal of cell biology. , 2002; 158(6): 1017-27.
Roesch K, Tranejaerg L, Koehler CM How do defects in mitochondrial protein import lead to deafness, 19th Danavox Symposium: Genetics and the function of the auditory system. , 2002; 19: 139-154.
Roesch K, Curran SP, Tranebjaerg L and Koehler CM Human deafness dystonia syndrome is caused by a defect in asssembly of the DDP1/TIMM8a-TIMM13 complex Hum. Mol. Gent, 2002; 11: 477-486.
Curran SP, Leuenberger D, Oppliger W, Koehler CM The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier The EMBO journal. , 2002; 21(5): 942-53.
Murphy MP, Leuenberger D, Curran SP, Oppliger W and Koehler CM The essential function of the small tim proteins in the tim22 import pathway does not depend on formation of the soluble 70-kilodalton complex Mol. Cell. Biol, 2001; 21: 6132-6138.
Renold A, Koehler CM and Murphy MP Mitochondrial import of the long and short isoforms of human uncoupling protein 3 FEBS Lett, 2000; 465: 135-140.
Koehler CM Protein translocation pathways of the mitochondrion FEBS Lett, 2000; 476(1-2): 27-31.
Dyall SM, Koehler CM, Delgadillo MG, Bradley PJ, Plumper E, Leuenberger D, Turck CW and Johnson PJ The presence of mitochondria carrier in the hydrogenosomal membranes: conservation of membrane targeting pathways indicated a progenitor organelle gave rise to hydrogenosomes and mitochondria Mol. Cell. Biol, 2000; 20: 2488-2497.
Koehler CM, Murphy MP, Bally NA, Oppliger W, Dolfini L, Junne T and Or E Tim18p, a novel subunit of the inner membrane complex that mediates protein import into the yeast mitochondrial inner membrane Mol. Cell. Biol, 2000; 20: 1187-1193.
Patterson SD, Spahr CS, Daugas E, Susin SA, Irinopoulou T, Koehler C, Kroemer G Mass spectrometric identification of proteins released from mitochondria undergoing permeability transition Cell death and differentiation. , 2000; 7(2): 137-44.
Koehler CM, Merchant S, Schatz G How membrane proteins travel across the mitochondrial intermembrane space Trends in biochemical sciences. , 1999; 24(11): 428-32.
Leuenberger D, Bally NA, Schatz G, Koehler CM Different import pathways through the mitochondrial intermembrane space for inner membrane proteins The EMBO journal. , 1999; 18(17): 4816-22.
Koehler CM, Leuenberger D, Merchant S, Renold A, Junne T and Schatz G Human deafness dystonia syndrome is a mitochondrial disease Proc. Natl. Acad. Sci. (USA), 1999; 96: 2141-2146.
Komiya T, Rospert S, Koehler CM, Looser R, Schatz G, and Mihara K Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: Evidence for the “acid chain” hypothesis, EMBO J, 1998; 17: 3886-3898.
Koehler CM, Merchant S, Oppliger W, Schmid K, Jarosch E, Dolfini L, Junne T, Schatz G and Tokatlidis K Tim9p, an essential partner of Tim10p for the import of mitochondrial carriers EMBO J, 1998; 17: 6477-6486.
Koehler CM, Jarosch E, Tokatlidis K, Schmid K, Schweyen RJ, Schatz G Import of mitochondrial carriers mediated by essential proteins of the intermembrane space Science. , 1998; 279(5349): 369-73.
Koehler CM, Myers AM Serine-threonine protein kinase activity of Elm1p, a regulator of morphologic differentiation in Saccharomyces cerevisiae FEBS letters. , 1997; 408(1): 109-14.
Blacketer MJ, Koehler CM, Coats SG, Myers AM, Madaule P Regulation of dimorphism in Saccharomyces cerevisiae: involvement of the novel protein kinase homolog Elm1p and protein phosphatase 2A Molecular and cellular biology. , 1993; 13(9): 5567-81.
Koehler CM, Lindber GL, BrownDR, Beitz DC, Freeman AE, Mayfield JE and Myers AM Replacement of bovine mitochondrial DNA by a sequence variant within a single generation, Genetics, 1991; 129: 247-255.
Biography
During his graduate and postdoctoral work with Harden McConnell at Stanford University, Wayne Hubbell used spin label technology to first describe the fluidity and fluidity gradient in biological membranes, landmark discoveries of broad impact in cell and membrane biology.
In 1970, he joined the faculty of the Department of Chemistry at UC Berkeley where his laboratory designed new surfactants, pioneered the molecular characterization of reconstituted membrane proteins, and developed a series of unique spin label probes to study membrane electrostatics.
In 1983, Prof. Hubbell moved his laboratory to UCLA where he became the first Jules Stein Professor of Ophthalmology and Professor of Chemistry and Biochemistry. Soon after arriving, he combined unrelated technical advancements in molecular biology and EPR spectroscopy and pioneered the powerful new technology of site-directed spin labeling (SDSL) for the determination of structure and conformational dynamics in both soluble and membrane proteins.
For his development and application of SDSL, Prof. Hubbell has received numerous honors and awards including the Gold Medal of the International EPR/ESR Society, the International Zavoisky Award from the Physical Technical Institute of the Russian Academy of Sciences, the Bruker Prize from the Royal Society of Chemistry-ESR Group, and the Elisabeth Roberts Cole from the Biophysical Society (US). He is a member of the National Academy of Sciences, American Academy of Arts and Sciences, elected to the first class of fellows of the Biophysical Society and recipient of an honorary doctorate from the University of Pécs, Hungary.