Last Revised:  July 2016
USC

Richard M. Watanabe, Ph.D.
Professor, Preventive Medicine and Physiology & Biophysics
Vice Chair for Education, Preventive Medicine

Degrees

B.S. Biological Sciences 1986 University of Southern California
M.S. Applied Biometry 1989 University of Southern California
Ph.D. Exercise Science 1995 University of Southern California


Professional Experience

Postdoctoral Fellow 1995-1998 University of Michigan, School of Public Health Associate Professor 2006-2014 Keck School of Medicine of USC
Dept. of Biostatistics Dept. of Preventive Medicine and Physiology & Biophysics
Research Investigator 1998-2000 University of Michigan, School of Public Health Vice Chair for Education 2012- Keck School of Medicine of USC
Dept. of Biostatistics Dept. of Preventive Medicine
Assistant Professor 2000-2006 Keck School of Medicine of USC Professor 2014- Keck School of Medicine of USC
Dept. of Preventive Medicine Dept. of Preventive Medicine and Physiology & Biophysics
Associate Program Director 2000-2010 Keck School of Medicine of USC
General Clinical Research Center


Research Interests

I have a primary interest in the pathophysiology and genetics of type 2 diabetes mellitus and obesity.  My current research focuses on:

Complex Disease Genetics
Genotype-phenotype Relationships
The Finland-United States Investigation of NIDDM Genetics (FUSION) study:   FUSION is a multi-center, international collaborative effort to identify genetic variation underlying risk for type 2 diabetes and diabetes-related traits in the Finnish population.  I have been involved in FUSION since graduate school and continue to be part of the study today.  FUSION is now a component of a number of large genetic consortia including DIAGRAM, MAGIC, GIANT, Global Lipids, GoT2D, and T2DGenes to name a few.  FUSION continues to examine the genetic architecture of type 2 diabetes and is now examining gene regulation in muscle and adipose tissues and in pancreatic beta-cells to better understand the role genetic variation plays in the risk for type 2 diabetes.
The BetaGene Study:  This is a study of Mexican American families of probands with and without a previous diagnosis of gestational diabetes mellitus.  We are interested in understanding how genetic variation alters basic physiology to contribute to the pathogenesis of type 2 diabetes.  The BetaGene Study is different from most human genetic studies in that we have performed detailed phenotyping and have precise measures of body composition, whole-body insulin sensitivity, insulin secretion and pancreatic beta-cell function.  In addition, we differ from other genetic studies in that we are focussed on gene-gene and gene-environment interactions that may play significant roles in the pathogenesis of type 2 diabetes.

Click here to see a complete list of BetaGene publications
The Genetics Underlying Diabetes in Hispanics (GUARDIAN) Study:  GUARDIAN is a consortium whose goal is to identify genetic loci underlying variation in insulin resistance and insulin clearance in the Hispanic population.  GUARDIAN is led by investigators from USC, Wake Forest University, and Cedars Sinai Medical Center.  GUARDIAN is perfoming a genome-wide association study of type 2 diabetes-related quantitative traits with translation into type 2 diabetes.  In particular, GUARDIAN is focussing on insulin resistance and insulin clearances as primary phenotypes of interest.
Pharmacogenetics of treatment and prevention of type 2 diabetes
We are examining the pharmacogenetics of the class of insulin-sensitizing agents known as thiazolidinediones (TZD), which are 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.

Mathematical Modeling of Physiologic Systems
Modeling kinetics of glucose, insulin, and lactate in humans
We are developing a series of models to estimate physiologic processes related to glucose metabolism through the analysis of kinetics of glucose, insulin, and lactate.
Modeling kinetics of glucose, insulin, and free-fatty acids in humans
We are developing a model of FFA kinetics that may allow us to partition whole-body insulin sensitivity into its hepatic and peripheral components.  Since this model would estimate these processes without the need for stable isotopes, the model could have applicability in a broad spectrum of metabolic research.
Physiological Genetic Modeling (PGM)
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.


Links for Prospective Graduate Students

   Dept of Preventive Medicine Graduate Programs:  Includes:  public health, biostatistics, epidemiology, molecular epidemiology, and health behavior.

   USC Programs in Biomedical and Biological Sciences (PIBBS):  PIBBS is the entry portal into our graduate programs in the laboratory sciences.  All entering students take a core curriculum while doing laboratory rotations.  At the end of the first year, students then choose to enter one of the interdisciplinary Ph.D. degree programs.

ATTENTION PIBBS STUDENTS INTERESTED IN DOING A ROTATION
All PIBBS students are more than welcome to do a rotation with us.   However, I want to make it very clear the research we do does not involve wet lab work.    Our work mainly involves the application of statistics, statistical genetics, bioinformatics, and physiology.  This means the computer is our main research tool and we work with data generated by our laboratory and clinical colleagues.  If after reading this notice you are still interested in a rotation, please feel free to contact me and we can discuss the possbilities.  Regardless, thanks very much for your interest in our work.



Photo Gallery


All photo links have been updated (July 2013) to public links to my Facebook albums.

Click here to access older photos (2008-2013)

Recent Photos

   "Oshogatsu" (New Years) Celebration at the Japanese American National Museum, January 2014

   Opening reception for 'Perseverance' (exhibit about tattoos in the Japanese tradition) at the Japanese American National Museum, March 2014

   Opening reception for 'Dodgers: Brotherhood of the Game'. A special collaboration between the Jackie Robinson family, the Dodgers organization, and the Japanese American National Museum, March 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 1 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 2 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 3 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 4 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 5 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 6 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 7 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 8 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 9 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 10 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 12 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Friends and Families of Nikkei Veterans 70th Annual Tour of France. Day 13 of a very special and memorable trip I took to learn more about the 100th Infantry Battalion and 442nd Regimental Combat Team, July 2014

   Natsumatsuri (Summer Festival) at the Japanese American National Museum and 6th Annual Tanabata Festival, August 2014

   74th Annual Nisei Week Festival closing ceremonies and street ondo, August 2014

   Vienna, September 2014

   Vienna (some of the stuff I ate), September 2014

   VIP opening reception for 'Hello! Exploring the Supercute World of Hello Kitty', October 2014

   "Oshogatsu" (New Years) Celebration at the Japanese American National Museum, January 2015

   Mini-reunion of a subset of the FFNV tour group held at The Far Bar in Little Tokyo, February 2015

   Closing Reception for 'Hello! Exploring the Supercute World of Hello Kitty', May, 2015

   Opening Reception Breakfast for "Before They Were Heroes - Sus Ito's World War II Images, July, 2015

   The 2015 Tanabata Festival, August 2015

   The 75th Annual Nisei Week Parade, August 2015

   75th Annual Nisei Week Festival closing ceremonies and street ondo, August 2015

   "Oshogatsu" (New Years) Celebration at the Japanese American National Museum, January 2016

   Day 1 in Japan, April 2016

   Day 2 in Japan, April 2016

   Day 3 in Japan, April 2016

   Day 4 in Japan, April 2016

   Day 5 in Japan, April 2016

   Day 6 in Japan, April 2016

   Day 7 in Japan, April 2016

   Day 8 in Japan, April 2016

   Day 9 in Japan, April 2016

   Day 10 in Japan, April 2016

   Days 11 and 12 in Japan, April 2016

   Above the Fold Openning Reception, Japanese American National Museum, May 2016



Miscellaneous


   My 5 seconds of fame: KTLA Photo Essay on the 70th Anniversary of Executive Order 9066, February, 2012

   My mug on the LA Coliseum jumbotron, September, 2015



Selected Recent Publications

*  indicates equal intellectual contribution or co-corresponding author; **  indicates member of consortium listed as co-author.

Stefanovski D, Youn JH, Rees M, Watanabe RM, Ader M, Ionut V, Jackson AU, Boehnke M, Collins FS, Bergman RN.  Estimating hepatic glucokinase activity using a simple model of lactate kinetics.  Diabetes Care 35:1015-1020, 2012.  PMID: 22456868

Chen Z, Black MH, Watanabe RM, Trigo E, Takayanagi M, Lawrence JM, Buchanan TA, Xiang AH.  Self-reported physical activity is associated with b-cell function in Mexican American adults.  Diabetes Care 36:638-644, 2013.  PMID: 23223346

Huyghe JR, Jackson AU, Fogarty MP, Buchkovich ML, Stancakova A, Stringham HM, Sim X, Yang L, Fuchsberger C, Cederberg H, Chines PS, Teslovich TM, Romm JM, Ling H, McMullen I, Ingersoll R, Pugh EW, Doheny KF, Neale BM, Daly MJ, Kuusisto J, Scott LJ, Kang HM, Collins FS, Abecasis GR, Watanabe RM, Boehnke M, Laakso M, Mohlke K.L.  Exome array analysis identifies novel loci and low-frequency variants for insulin processing and secretion.  Nat Genet 45:197-201, 2013.  PMID: 23263489

Black MH, Watanabe RM, Trigo E, Takayanagi M, Lawrence JM, Buchanan TA, Xiang AH.  High-fat diet is associated with obesity-mediated insulin resistance and cell dysfunction in Mexican Americans.  J Nutr 143:479-485, 2013.  PMID: 23343677

Kashyap SR, Bhatt DL, Wolski K, Watanabe RM, Abdul-Ghani M, Abood B, Pothier CE, Brethauer S, Nissen S, Gupta M, Kirwan JP, Schauer PR.  Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment.  Diabetes Care 36:2175-82, 2013  PMID: 23439632

Xiang AH, Takayanagi M, Black MH, Trigo E, Lawrence JM, Watanabe RM, Buchanan TA.  Longitudinal changes in insulin sensitivity and beta cell function between women with and without a history of gestational diabetes mellitus.  Diabetologia 56:2753-60, 2013  PMID: 24030069

Goodarzi MO, Langefeld CD, Xiang AH, Chen YD, Guo X, Hanley AJ, Raffel LJ, Kandeel F, Nadler JL, Buchanan TA, Norris JM, Fingerlin TE, Lorenzo C, Rewers MJ, Haffner SM, Bowden DW, Rich SS, Bergman RN, Rotter JI, Watanabe RM, Wagenknecht LE.  Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans.  Obesity (Silver Spring) 22:1157-64, 2014  PMID: 24124113

Dimas AS, Lagou V, Barker A, Knowles JW, Mägi R, Hivert MF, Benazzo A, Rybin D, Jackson AU, Stringham HM, Song C, Fischer-Rosinsky A, Boesgaard TW, Grarup N, Abbasi FA, Assimes TL, Hao K, Yang X, Lecoeur C, Barroso I, Bonnycastle LL, Böttcher Y, Bumpstead S, Chines PS, Erdos MR, Graessler J, Kovacs P, Morken MA, Narisu N, Payne F, Stancakova A, Swift AJ, Tönjes A, Bornstein SR, Cauchi S, Froguel P, Meyre D, Schwarz PE, Häring HU, Smith U, Boehnke M, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, Quertemous T, Lind L, Hansen T, Pedersen O, Walker M, Pfeiffer AF, Spranger J, Stumvoll M, Meigs JB, Wareham NJ, Kuusisto J, Laakso M, Langenberg C, Dupuis J, Watanabe RM*, Florez JC*, Ingelsson E*, McCarthy MI*, Prokopenko I*; MAGIC Investigators.  Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.  Diabetes 63:2158-71, 2014.  PMID: 24296717

Xiang AH, Watanabe RM, Buchanan TA.  OMA and Matsuda indices of insulin sensitivity: poor correlation with minimal model-based estimates of insulin sensitivity in longitudinal settings.  Diabetologia 57:334-8, 2014.  PMID: 24305964

Ren J, Xiang AH, Trigo E, Takayanagi M, Beale E, Lawrence JM, Hartiala J, Richey JM, Allayee H, Buchanan TA, Watanabe RM.  Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans.  Diabetologia 57:1391-1399, 2014.  PMID: 24728128

Palmer ND, Goodarzi MO, Langefeld CD, Wang N, Guo X, Taylor KD, Fingerlin TE, Norris JM, Buchanan TA, Xiang AH, Haritunians T, Ziegler JT, Williams AH, Stefansovski D, Cui J, Mackay AW, Henkin LF, Bergman RN, Gao X, Gauderman J, Varma R, Hanis CL, Cox NJ, Highland HM, Below JE, Williams AL, Burtt NP, Aguilar-Salinas CA, Huerta-Chagoya A, Gonzalez-Villalpando C, Orozco L, Haiman CA, Tsai MY, Johnson WC, Yao J, Rasmussen-Torvik L, Pankow J, Snively B, Jackson RD, Liu S, Nadler JL, Kandeel F, Chen YI, Bowden DW, Rich SS, Raffel LJ, Rotter JI*, Watanabe RM*, Wagenknecht LE*.  Genetic Variants Associated with Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.  Diabetes 64:1853-1866, 2015.  PMID: 25524916

Black MH, Wu J, Takayanagi M, Wang N, Taylor KD, Haritunians T, Trigo E, Lawrence JM, Watanabe RM, Buchanan TA, Xiang AH.  Variantion in PPARG is associated with longitudinal change in insulin resistance in Mexican Americans at risk for type 2 diabetes.  J Clin Endocrinol Metab 100:1187-1195, 2015.  PMID: 25584717

Mahajan A, Sim X, Ng HJ, Manning A, Rivas MA, Highland HM, Locke AE, Grarup N, Im HK, Cingolani P, Flannick J, Fontanillas P, Fuchsberger C, Gaulton KJ, Teslovich TM, Rayner NW, Robertson NR, Beer NL, Rundle JK, Bork-Jensen J, Ladenvall C, Blancher C, Buck D, Buck G, Burtt NP, Gabriel S, Gjesing AP, Groves CJ, Hollensted M, Huyghe JR, Jackson AU, Jun G, Justesen JM, Mangino M, Murphy J, Neville M, Onofrio R, Small KS, Stringham HM, Syvänen AC, Trakalo J, Abecasis G, Bell GI, Blangero J, Cox NJ, Duggirala R, Hanis CL, Seielstad M, Wilson JG, Christensen C, Brandslund I, Rauramaa R, Surdulescu GL, Doney AS, Lannfelt L, Linneberg A, Isomaa B, Tuomi T, Jørgensen ME, Jørgensen T, Kuusisto J, Uusitupa M, Salomaa V, Spector TD, Morris AD, Palmer CN, Collins FS, Mohlke KL, Bergman RN, Ingelsson E, Lind L, Tuomilehto J, Hansen T, Watanabe RM, Prokopenko I, Dupuis J, Karpe F, Groop L, Laakso M, Pedersen O, Florez JC, Morris AP, Altshuler D, Meigs JB, Boehnke M, McCarthy MI, Lindgren CM, Gloyn AL; T2D-GENES consortium and GoT2D consortium.  Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.  PLoS Genet 11:e1004876, 2015.  PMID: 25625282

Chen Z, Salam MT, Karim R, Toledo-Corral CM, Watanabe RM, Xiang AH, Buchanan TA, Habre R, Bastain TM, Lurmann F, Taher M, Wilson JP, Trigo E, Gilliland FD.  Living near a freeway is associated with lower bone mineral density among Mexican Americans.  Osteoporos Int 26:1713-1721, 2015.  PMID: 25677718

Sharma PR, Mackey AJ, Dejene EA, Ramadan JW, Langefeld CD, Palmer ND, Taylor KD, Wagenknecht LE, Watanabe RM, Rich SS, Nunemaker CS.  An islet-targeted genome-wide association scan identifies novel genes implicated in cytokine-mediated islet stress in type 2 diabetes.  Endocrinology 156:3147-3156, 2015.  PMID: 26018251

Gao C, Wang N, Buo X, Ziegler JT, Talor KD, Xiang AH, Hai Y, Dridel SJ, Nadler JL, Kandeel F, Raffel LJ, Chen YD, Norris JM, Rotter JI, Watanabe RM, Wagenknecht LE, Bowden DW, Speliotes EK, Goodarzi MO, Langefeld CD, Palmer ND.  A comprehensive analysis of common and rare variants to identify adiposity loci in Hispanic Americans: The IRAS Family Study (IRASFS).  PLoS One 10:e0134649, 2015.  PMID: 26599207

Palmer ND, Wagenknecht LE, Langefeld, CD, Wang N, Buchanan TA, Xiang AH, Allayee H, Bergman RN, Raffel LJ, Chen YD, Hartunians T, Fingerlin T, Goodarzi MO, Taylor KD, Rotter JI, Watanabe RM, Bowden DW.  Improved performance of dynamic measures of insulin response over surrogate indices to identify genetic contributors of type 2 diabetes: The GUARDIAN Consortium.  Diabetes 65:2072-2080, 2016.  PMID: 27207554

Scott LJ, Erdos MR, Huyghe JR, Welch RP, Beck AT, Wolford BN, Chines PS, Didion JP, Narisu N, Stringham HM, Taylor DL, Jackson AU, Vadlamudi S, Bonnycastle LL, Kinnunen L, Saramies J, Sundvall J, Albanus RD, Kiseleva A, Hensley J, Crawford GE, Jiang H Wen X, Watanabe RM, Lakka TA, Mohlke KL, Laakso M, Tuomilehto J, Koistinen HA, Boehnke M, Collins FS, Parker SC.  The genetic regulatory signature of type 2 diabetes in human skeletal muscle.  Nat Commun 7:11764, 2016.  PMID: 27353450

Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, et al..  The genetic architecture of type 2 diabetes.  Nature, 2016 (Epub ahead of print).  PMID: 27398621



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Copyright: 2002-2016 Richard M. Watanabe