Roth, Michael - UT Southwestern Medical Center

个人简介

Biography Michael Roth received an AB degree in 1971 from Davidson College and taught high school science in Alexandria Virginia before obtaining a PhD in Cell and Molecular Biology from the University of Alabama at Birmingham in 1982. He was a Damon Runyon Cancer Research Foundation postdoctoral fellow from 1982-1983 and a NIH postdoctoral fellow from 1983-1985 with Drs. Joe Sambrook and Mary-Jane Gething at Cold Spring Harbor Laboratory. He joined the faculty at UT Southwestern in 1985, was promoted to professor in 1996 and that year received the Diane and Hal Brierley Chair in Biomedical Research. Dr. Roth’s current research interests focus on drug discovery. Active research programs in the Roth laboratory target virus pathogens, cancer and diabetes with an emphasis in using genetics and cell biology to determine the mechanisms by which novel chemical compounds affect living organisms. Dr. Roth is a founding member of the University of Texas Academy of Health Science Education and a member of Southwestern Academy of Teachers. Education Undergraduate Davidson College (1971), French Literature Graduate School University of Alabama at Birmingham (1982) Honors & Awards UT Southwestern Academy of Teachers (2011) Distinguished Teaching Professor (2005) Member, UT Academy of Health Science Education (2005) Diane and Hal Brierley Distinguished Chair in Biomedical Research (1996) Established Investigator of the American Heart Association

研究领域

Research in the Roth lab focuses on discovering drug-like small molecules that have interesting biological properties and then determining the mechanisms by which they act. This is a research strategy that is logically identical to classical forward genetics, with the difference that we identify a bioactive chemical rather than a mutation in a target gene. Like classical genetics, we let nature tell us what biology is most relevant to a process. An advantage to this is that we are not limited to making guesses from what has already been discovered. Our experiments probe all of the biological space, not just the corner we know about. Recently we have discovered chemicals that act on host cell processes to prevent virus infections, chemicals that selectively kill some non-small cell lung cancer but not normal cells, and chemicals that suppress the production of glucagon by an alpha cell line. Currently we are investigating the mode of action of these chemicals as well as determining their molecular targets. In collaborations with chemists and pharmacologists at UT Southwestern, we are trying to improve the potency and pharmacological properties of these chemicals so that they might become useful leads for developing therapeutic drugs. Research Interest antiviral therapeutics, viruses, host defense against virus Biochemistry and Cell Biology Diabetes, Type I & II Drug discovery High-throughput screening of chemical compound libraries. High-throughput screening of RNAi libraries. Intracellular traffic in membrane proteins and lipids. Lung Cancer

近期论文

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Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway. Wang MY, Yan H, Shi Z, Evans MR, Yu X, Lee Y, Chen S, Williams A, Philippe J, Roth MG, Unger RH Proc. Natl. Acad. Sci. U.S.A. 2015 Feb 112 8 2503-8 A New Biology of Diabetes Revealed by Leptin. Unger RH, Roth MG Cell Metab. 2014 Nov Hyperglycemia in rodent models of type 2 diabetes requires insulin-resistant alpha cells. Lee Y, Berglund ED, Yu X, Wang MY, Evans MR, Scherer PE, Holland WL, Charron MJ, Roth MG, Unger RH Proc. Natl. Acad. Sci. U.S.A. 2014 Aug Systematic identification of molecular subtype-selective vulnerabilities in non-small-cell lung cancer. Kim HS, Mendiratta S, Kim J, Pecot CV, Larsen JE, Zubovych I, Seo BY, Kim J, Eskiocak B, Chung H, McMillan E, Wu S, De Brabander J, Komurov K, Toombs JE, Wei S, Peyton M, Williams N, Gazdar AF, Posner BA, Brekken RA, Sood AK, Deberardinis RJ, Roth MG, Minna JD, White MA Cell 2013 Oct 155 3 552-66 Studies toward the Unique Pederin Family Member Psymberin: Structure-Activity Relationships, Biochemical Studies and Genetics Identify the Mode-of-Action of Psymberin. Wu CY, Feng Y, Cardenas ER, Williams NS, Floreancig PE, De Brabander JK, Roth MG J. Am. Chem. Soc. 2012 Oct Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export. Zhang L, Das P, Schmolke M, Manicassamy B, Wang Y, Deng X, Cai L, Tu BP, Forst CV, Roth MG, Levy DE, García-Sastre A, de Brabander J, Phillips MA, Fontoura BM J. Cell Biol. 2012 Feb 196 3 315-26 Image-based genome-wide siRNA screen identifies selective autophagy factors. Orvedahl A, Jr RS, Xiao G, Ng A, Zou Z, Tang Y, Narimatsu M, Gilpin C, Sun Q, Roth M, Forst CV, Wrana JL, Zhang YE, Luby-Phelps K, Xavier RJ, Xie Y, Levine B Nature 2011 Oct Chemical inhibition of RNA viruses reveals REDD1 as a host defense factor. Mata MA, Satterly N, Versteeg GA, Frantz D, Wei S, Williams N, Schmolke M, Peña-Llopis S, Brugarolas J, Forst CV, White MA, García-Sastre A, Roth MG, Fontoura BM Nat. Chem. Biol. 2011 7 10 Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan CW, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L Nat. Chem. Biol. 2009 Feb 5 2 100-7 Targetting QseC Signaling and Virulence for Antibiotic Development Rasko, D. A. C. G. Moreira, D. Li, J. M. Ritchie, M. K. Waldor, N. Williams, R. Taussig, C. Mischnoff, S. Wei, M. G. Roth, D. T. Hughes, J. Huntley, J. R. Falck, and V. Sperandio Science 2008 321 1078-1080 Synthetic lethal screen identification of chemosensitizer loci in cancer cells. Whitehurst AW, Bodemann BO, Cardenas J, Ferguson D, Girard L, Peyton M, Minna JD, Michnoff C, Hao W, Roth MG, Xie XJ, White MA Nature 2007 Apr 446 7137 815-9 The hedgehog pathway effector smoothened exhibits signaling competency in the absence of ciliary accumulation. Fan CW, Chen B, Franco I, Lu J, Shi H, Wei S, Wang C, Wu X, Tang W, Roth MG, Williams NS, Hirsch E, Chen C, Lum L Chem. Biol. 2014 Dec 21 12 1680-9 Genome-wide siRNA screen reveals coupling between mitotic apoptosis and adaptation. Díaz-Martínez LA, Karamysheva ZN, Warrington R, Li B, Wei S, Xie XJ, Roth MG, Yu H EMBO J. 2014 Jul Characterization of Cholesterol Homeostasis in Telomerase-Immortalized Tangier Disease Fibroblasts Reveals Marked Phenotype Variability. Kannenberg F, Gorzelniak K, Jager K, Fobker M, Rust S, Repa J, Roth M, Bjorkhem I, Walter M J. Biol. Chem. 2013 Nov TDP-43 Identified from a Genome Wide RNAi Screen for SOD1 Regulators. Somalinga BR, Day CE, Wei S, Roth MG, Thomas PJ PLoS ONE 2012 7 4 e35818 Host modulators of H1N1 cytopathogenicity. Ward SE, Kim HS, Komurov K, Mendiratta S, Tsai PL, Schmolke M, Satterly N, Manicassamy B, Forst CV, Roth MG, García-Sastre A, Blazewska KM, McKenna CE, Fontoura BM, White MA PLoS ONE 2012 7 8 e39284 The non-catalytic carboxyl-terminal domain of ARFGAP1 regulates actin cytoskeleton reorganization by antagonizing the activation of Rac1. Siu KY, Yu MK, Wu X, Zong M, Roth MG, Chan HC, Yu S PLoS ONE 2011 6 4 e18458 Towards patient-based cancer therapeutics. Schreiber SL, Shamji AF, Clemons PA, Hon C, Koehler AN, Munoz B, Palmer M, Stern AM, Wagner BK, Powers S, Lowe SW, Guo X, Krasnitz A, Sawey ET, Sordella R, Stein L, Trotman LC, Califano A, Dalla-Favera R, Ferrando A, Iavarone A, Pasqualucci L, Silva J, Stockwell BR, Hahn WC, Chin L, DePinho RA, Boehm JS, Gopal S, Huang A, Root DE, Weir BA, Gerhard DS, Zenklusen JC, Roth MG, White MA, Minna JD, MacMillan JB, Posner BA Nat. Biotechnol. 2010 Sep 28 9 904-6 Mitochondrial dysfunction confers resistance to multiple drugs in Caenorhabditis elegans. Zubovych IO, Straud S, Roth MG Mol. Biol. Cell 2010 Mar 21 6 956-69 Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines. Straud S, Zubovych I, De Brabander JK, Roth MG PLoS ONE 2010 5 7 e11629