Department of Pharmacology, Physiology and Toxicology
Research Cluster: Cardiovascular Disease, Obesity, and Diabetes
Office: BBSC 435-K
Phone: 304-696-3873 | Fax: 304-696-7391
My long-term research interest is in understanding the etiology and mechanisms underlying Type 2 diabetes and obesity, concomitantly related diseases. Type 2 diabetes is the most common form of human diabetes, accounting for over 90% of cases. Obesity at such epidemic proportions creates serious public health problems. Both diseases, furthermore, are associated with chronic complications and cardiovascular disease, increasing morbidity as well as mortality.
There is substantial evidence demonstrating that genetic factors are strongly involved in the development of Type 2 diabetes and obesity, and I have focused my attention on the link between gene dysfunction and these diseases.
Currently, I seek to understand the molecular basis of an obesity susceptibility gene on mouse chromosome 6, named tabw2, derived from the TALLYHO (TH) mouse model for polygenic Type 2 diabetes and obesity. Tabw2 gene appears to interact with high fat/ high sucrose diets to make mice overtly obese. In that respect it is an excellent model for human obesity, which most often results from interactions between genetic susceptibility and an obesity promoting environment – i.e., diets enriched in calories from fat and sugar. Therefore, understanding the molecular basis for diet-induced obesity in tabw2 mutant mice may uncover new cellular regulatory pathways that can then be exploited in the control of human obesity.
I also seek to understand the molecular basis of a diabetes susceptibility gene on mouse chromosome 4, tanidd4, and an obesity susceptibility gene on mouse chromosome 1, tabw3, derived both from the TH mice. The diabetogenic and obesigenic effects of TH alleles at these loci have been confirmed by congenic mice strategy. Physiological and biochemical characterizations of diabetes and obesity mediated by these loci are also on going using the congenic mouse strains.
My continued research will include gene discovery, genetic resource development, and biochemical and physiological studies associated with Type 2 diabetes and obesity.
Mao X, Dillon KD, McEntee MF, Saxton AM, and Kim JH. Islet insulin secretion, b-cell mass, and energy balance in a polygenic mouse model of Type 2 diabetes with obesity. Journal of Inborn Errors of Metabolism & Screening 2014: 1-6.
Stewart TP, Mao X, Aqqad MN, Uffort D, Dillon KD, Saxton AM, and Kim JH. Subcongenic analysis of tabw2 obesity QTL on mouse chromosome 6. BMC Genet 2012, 13(1): 81.
Fletcher SJ, Kalupahana NS, Soltani-Bejnood M, Kim JH, Saxton AM, Wasserman DH, De Taeye B, Voy BH, Quignard-Boulange A, Moustaid-Moussa N. Transgenic mice overexpressing Renin exhibit glucose intolerance and diet-genotype interactions. Front Endocrinol (Lausanne) 2012, 3: 166.
Kim JH and Saxton AM. The TALLYHO mouse as a model of human type 2 diabetes. Methods Mol Biol 2012, 933: 75-87.
Kim HY, Stewart TP, Wyatt BN, Siriwardhana N, Saxton AM, Kim JH. Gene expression profiles of a mouse congenic strain carrying an obesity susceptibility QTL under obesigenic diets. Genes & Nutrition 2010, 5: 237-250.
Jacaline K. Parkman, B.S. – Research M.S. student