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. The 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 the congenic mice strategy. Physiological and biochemical characterizations of diabetes and obesity mediated by these loci are also ongoing 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.