Richard M. Watanabe, Ph.D. Associate Professor, Preventive Medicine and Physiology & Biophysics Associate Program Director, General Clinical Research Center

Degrees

Professional Experience

Research Interests

Complex Disease Genetics
			Positional cloning of complex disease genes
			The Finland-United States Investigation of NIDDM Genetics (FUSION) study:   This is a multi-center, international collaborative effort to positionally clone genes for type 2 diabetes and diabetes-related traits in the Finnish population.  FUSION is one of the largest among the various positional cloning studies and has extensively phenotyped many of its participants.  Our work on FUSION mainly focusses on the analysis and interpretation of quantitative trait data.
			The BetaGene Study:  This is a study designed to identify the genetic determinants of beta-cell dysfunction in families of Mexican-American women who have had gestational diabetes.  This is a family-based positional cloning study where we are recruiting and extensively phenotyping large Mexican-American families with the goal of performing genome-wide QTL linkage analysis.  In addition, our sampling scheme includes a case-control sample to allow association testing of candidate genes.
			Pharmacogenetics of treatment and prevention of type 2 diabetes.
			We are currently examining the pharmacogenetics of the class of insulin-sensitizing agents known as thiazolidinediones (TZD), which are currently used to treat people with type 2 diabetes.  Approximately 30-45% of people do not respond to TZD treatment.  We are attempting to dissect the genetic architecture underlying response to these medications.
			Physiological Genetic Modeling (PGM)
			PGM is a framework by which physiologic models are used to assess the effect of genetic variation on biology.  We are developing a physiologically-based compartmental model of glucose metabolism to simulate glucose and insulin patterns that might be observed during the course of specific clinical tests.  We then impose "genes" on different parameters of the model to assess single gene and multigenic effects.  PGM is an alternative means to assess gene-gene and gene-environment interactions and also provides a framework for testing statistical genetic methods designed to detect and characterize genetic variation.

Mathematical Modeling of Physiologic Systems
			Modeling kinetics of glucose, insulin, and lactate in humans
			Modeling kinetics of glucose, insulin, and free-fatty acids in humans

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Our Research in the News

USC Diabetes in the News

Recent Publications

Shtir C, Nagakawa IS, Duren WL, Conneely, KN, Scott LJ, Silander K, Valle TT, Tuomilehto J, Buchanan TA, Bergman RN, Collins FS, Boehnke M, Watanabe RM.  Subsets of Finns with high HDL to total cholesterol ratio show evidence for linkage to type 2 diabetes on chromosome 6q.  Human Heredity 63:17-25, 2007.  PMID: 17179727

Willer CJ, Bonnycastle LL, Conneely KN, Duren WL, Jackson AU, Scott LJ, Narisu N, Chines PS, Skol A, Stringham HM, Petrie J, Erdos MR, Swift AJ, Enloe ST, Sprau AG, Smith E, Tong M, Doheny KF, Pugh EW, Watanabe RM, Buchanan TA, Valle TT, Bergman RN, Tuomilehto J, Mohlke KL, Collins FS, Boehnke M.  Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes.  Diabetes 56:256-264, 2007.  PMID: 17192490

Watanabe RM, Allayee H, Xiang AH, Trigo E, Hartiala J, Lawrence JM, Buchanan TA.  Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes and interacts with adiposity to alter insulin secretion in Mexican Americans.  Diabetes 56:1481-1485, 2007.  PMID: 17317761

Watanabe RM, Black MH, Xiang AH, Allayee H, Lawrence JM, Buchanan TA.  Genetics of GDM and Type 2 Diabetes.  Diabetes Care, 30(Suppl 2):S134-S140, 2007.  PMID: 17596461

Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, Prokunina-Olsson L, Ding C-J, Swift AJ, Narisu N, Hu T, Pruim R, Xiao R, Li X-Y, Conneely KN, Riebow NL, Sprau AG, Tong M, White PP, Hetrick KN, Barnhart MW, Bark CW, Goldstein JL, Watkins L, Xiang F, Saramies J, Buchanan TA, Watanabe RM, Valle TT, Kinnunen L, Abecasis GR, Pugh EW, Doheny KF, Bergman RN, Tuomilehto J, Collins FS, Boehnke M.  Genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.  Science, 316:1341-1345, 2007.  PMID: 17463248

Li C, Li M, Lange EM, Watanabe RM.  Prioritized subset analysis:  Improving power in genome-wide association studies.  Human Heredity, 65:129-141, 2008.  PMID: 17934316

Millis MP, Bowen D, Kingsley C, Watanabe RM, Wolford JK.  Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes.  Diabetes 56:3027-3032, 2007.  PMID: 17881614

Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, Heath SC, Timpson NJ, Najjar SS, Stringham HM, Strait J, Duren WL, Maschio A, Busonero F, Mulas A, Albai G, Swift AJ, Morken MA, Narisu N, Bennett D, Parish S, Shen H, Galan P, Meneton P, Herçberg S, Zelenika S, Chen W.-M, Li Y, Scott LJ, Scheet PA, Sundvall J, Watanabe RM, Nagaraja R, Ebrahim S, Lawlor DA, Ben-Sholomo Y, Davey-Smith G, Shuldiner AR, Collins R, Bergman RN, Uda M, Tuomilehto J, Cao A, Collins FS, Lakatta E, Lathrop GM, Boehnke M, Schlessinger D, Mohlke KL, Abecasis GR.  Newly identified loci that influence lipid concentrations and risk of coronary artery disease.  Nature Genetics, 40:161-169, 2008.  PMID: 18193043

Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen W-M, Bonnycastle LL, Shen H, Timpson N, Lettre G, Usala G, Chines PS, Stringham HM, Scott LJ, Dei M, Lai S, Albai G, Crisponi L, Naitza S, Doheny KF, Pugh EW, Sholomo YB, Ebrahim S, Lawlor DA, Bergman RN, Watanabe RM, Uda M, Tuomilehto J, Coresh J, Hirschhorn JN, Shuldiner AR, Schlessinger D, Collins FS, Davey Smith G, Boerwinkle E, Cao A, Boehnke M, Abeçasis GR, Mohlke KL.  Common variants in the GDF5 - UQCC region are associated with variation in human height.  Nature Genetics, 40:198-203, 2008.  PMID: 18193045

Black MH, Fingerlin TE, Allayee H, Zhang W, Xiang AH, Trigo E, Hartiala J, Lehtinen, AB, Haffner SM, Bergman RN, McEachin RC, Kjos SL, Lawrence JM, Buchanan TA, Watanabe RM.  Interaction between peroxisome proliferator-activated receptor-g (PPARG2) and hepatocyte nuclear factor-4a (HNF4A) is associated with insulin sensitivity in Mexican Americans.  Diabetes, 57:1048-1056, 2008.  PMID: 18162503

Chang AJ, Kline MM, Currie Y, Wijesuriya H, Perez-Ospina M, Hartiala J, Buchanan TA, Watanabe RM, Allayee H.  Allgrove syndrome in a Mexican American family is caused by an ancestral mutation derived from North Africa.  Clinical Genetics, 73:385-387, 2008.  PMID: 18261130

Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T, de Bakker PI, Abecasis GR, Almgren P, Andersen G, Ardlie K, Boström KB, Bergman RN, Bonnycastle LL, Borch-Johnsen K, Burtt NP, Chen H, Chines PS, Daly MJ, Deodhar P, Ding CJ, Doney AS, Duren WL, Elliott KS, Erdos MR, Frayling TM, Freathy RM, Gianniny L, Grallert H, Grarup N, Groves CJ, Guiducci C, Hansen T, Herder C, Hitman GA, Hughes TE, Isomaa B, Jackson AU, Jørgensen T, Kong A, Kubalanza K, Kuruvilla FG, Kuusisto J, Langenberg C, Lango H, Lauritzen T, Li Y, Lindgren CM, Lyssenko V, Marvelle AF, Meisinger C, Midthjell K, Mohlke KL, Morken MA, Morris AD, Narisu N, Nilsson P, Owen KR, Palmer CN, Payne F, Perry JR, Pettersen E, Platou C, Prokopenko I, Qi L, Qin L, Rayner NW, Rees M, Roix JJ, Sandbæk A, Shields B, Sjögren M, Steinthorsdottir V, Stringham HM, Swift AJ, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tuomi T, Tuomilehto J, Walker M, Watanabe RM, Weedon MN, Willer CJ; Wellcome Trust Case Control Consortium, Illig T, Hveem K, Hu FB, Laakso M, Stefansson K, Pedersen O, Wareham NJ, Barroso I, Hattersley AT, Collins FS, Groop L, McCarthy MI, Boehnke M, Altshuler D.  Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.  Nature Genetics, 40:638-645, 2008.  PMID: 18372903

Chen WM, Erdos MR, Jackson AU Saxena R, Sanna S, Silver KD, Timpson N, Hansen, T, Orru M, Piras MG, Bonnycastle LL, Willer CJ, Lyssenko V, Haiqing S, Kuusisto J, Ebrahim S, Sestu N, Duren WL, Spada MC, Stringham HM, Scott LJ, Olla N, Swift AJ, Najjar S, Mitchell BD, Lawlor DA, Davey Smith G, Ben-Shlomo Y, Andersen G, Borch-Johnsen K, Jorgensen T, Saramies J, Valle TT, Buchanan TA, Shuldiner AR, Lakatta E, Bergman RN, Uda M, Tuomilehto J, Pedersen O, Cao A, Groop L, Mohlke KL, Laakso M, Schlessinger D, Collins FS, Altshuler D, Abecasis GR, Boehnke M, Scuteri A, Watanabe RM.  Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.  Journal of Clinical Investigation, 118:2620-2628, 2008.  PMID: 18521185

Hucking K, Watanabe RM, Stefanovski D, Bergman RN.  OGTT-derived measures of insulin senstivity are confounded by factors other than insulin sensitivity itself.  Obesity (Sliver Springs), 16:1938-1945, 2008.  PMID: 18670420

Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, Loos RJ, Manning AK, Jackson AU, Aulchenko Y, Potter SC, Erdos MR, Sanna S, Hottenga JJ, Wheeler E, Kaakinen M, Lyssenko V, Chen WM, Ahmadi K, Beckmann JS, Bergman RN, Bochud M, Bonnycastle LL, Buchanan TA, Cao A, Cervino A, Coin L, Collins FS, Crisponi L, de Geus EJ, Dehghan A, Deloukas P, Doney AS, Elliott P, Freimer N, Gateva V, Herder C, Hofman A, Hughes TE, Hunt S, Illig T, Inouye M, Isomaa B, Johnson T, Kong A, Krestyaninova M, Kuusisto J, Laakso M, Lim N, Lindblad U, Lindgren CM, McCann OT, Mohlke KL, Morris AD, Naitza S, Orrù M, Palmer CN, Pouta A, Randall J, Rathmann W, Saramies J, Scheet P, Scott LJ, Scuteri A, Sharp S, Sijbrands E, Smit JH, Song K, Steinthorsdottir V, Stringham HM, Tuomi T, Tuomilehto J, Uitterlinden AG, Voight BF, Waterworth D, Wichmann HE, Willemsen G, Witteman JC, Yuan X, Zhao JH, Zeggini E, Schlessinger D, Sandhu M, Boomsma DI, Uda M, Spector TD, Penninx BW, Altshuler D, Vollenweider P, Jarvelin MR, Lakatta E, Waeber G, Fox CS, Peltonen L, Groop LC, Mooser V, Cupples LA, Thorsteinsdottir U, Boehnke M, Barroso I, Van Duijn C, Dupuis J, Watanabe RM, Stefansson K, McCarthy MI, Wareham NJ, Meigs JB, Abecasis GR.  Variants in MTNR1B influence fasting glucose levels.  Nature Genetics 41:77-81, 2009.  PMID: 19060907

Lyssenko V, Nagorny CL, Erdos MR, Wierup N, Jonsson A, Spégel P, Bugliani M, Saxena R, Fex M, Pulizzi N, Isomaa B, Tuomi T, Nilsson P, Kuusisto J, Tuomilehto J, Boehnke M, Altshuler D, Sundler F, Eriksson JG, Jackson AU, Laakso M, Marchetti P, Watanabe RM, Mulder H, Groop L.  Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.  Nature Genetics 41:82-88, 2009.  PMID: 19060908

Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP, Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD, Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM, Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D, Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB, Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P, Kuokkanen M, Kuusisto J, Laitinen J, Lakatta EG, Luan J, Luben RN, Mangino M, McArdle WL, Meitinger T, Mulas A, Munroe PB, Narisu N, Ness AR, Northstone K, O'Rahilly S, Purmann C, Rees MG, Ridderstråle M, Ring SM, Rivadeneira F, Ruokonen A, Sandhu MS, Saramies J, Scott LJ, Scuteri A, Silander K, Sims MA, Song K, Stephens J, Stevens S, Stringham HM, Tung YC, Valle TT, Van Duijn CM, Vimaleswaran KS, Vollenweider P, Waeber G, Wallace C, Watanabe RM, Waterworth DM, Watkins N; Wellcome Trust Case Control Consortium, Witteman JC, Zeggini E, Zhai G, Zillikens MC, Altshuler D, Caulfield MJ, Chanock SJ, Farooqi IS, Ferrucci L, Guralnik JM, Hattersley AT, Hu FB, Jarvelin MR, Laakso M, Mooser V, Ong KK, Ouwehand WH, Salomaa V, Samani NJ, Spector TD, Tuomi T, Tuomilehto J, Uda M, Uitterlinden AG, Wareham NJ, Deloukas P, Frayling TM, Groop LC, Hayes RB, Hunter DJ, Mohlke KL, Peltonen L, Schlessinger D, Strachan DP, Wichmann HE, McCarthy MI, Boehnke M, Barroso I, Abecasis GR, Hirschhorn JN; Genetic Investigation of ANthropometric Traits Consortium.  Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.  Nature Genetics 41:25-34, 2009.  PMID: 19079261

Li X, Allayee H, Xiang AH, Trigo E, Hartiala J, Lawrence JM, Buchanan TA, Watanabe RM.  Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans.  Obesity (Silver Springs), 17:729-736, 2009.  PMID: 19148120

Send Richard E-mail:  rwatanab@usc.edu

Copyright: 2002-2009 Richard M. Watanabe