Stephen D. Hursting, M.P.H., Ph.D.

Professor, Human Ecology
The University of Texas at Austin
Member Research Focus Area 3
shursting@mail.utexas.edu

Education

Earlham College, Richmond, IN, B.A., Biology
University of North Carolina, Chapel Hill, NC, M.P.H, 1992, Nutritional Epidemiology
University of North Carolina, Chapel Hill, NC, Ph.D., Nutritional Biochemistry

Research Interests

• Diet-gene interactions relevant to cancer prevention
• Molecular and hormonal mechanisms underlying energy balance-cancer associations

Our work has focused on developing and using genetically altered mouse models to identify preventive, particularly nutritional, approaches to offset the increased cancer risk due to a genetic lesion such as loss of p53 or APC tumor suppressor activity or overexpression of growth signaling molecules including Wnt-1 and insulin-like growth factor-1 (IGF-1). We have reported that calorie restriction (CR) in p53-null (-/-) mice, Apc min, and Wnt-1 transgenic mice prevents adult-onset obesity, increases the latency of spontaneous tumor development, and decreases serum IGF-1 and leptin levels. In contrast, diet-induced obesity in these model systems enhances tumor development and increase levels of IGF-1 and leptin, as well as markers of insulin resistance and inflammation. Using diabetic A-Zip/F1 transgenic mice, which lack white adipose tissue but display insulin resistance, inflammation and increased tumor susceptibility, we are working to dissociate the relative roles of adiposity, insulin/IGF-1/leptin (and their associated signaling pathways) and inflammatory factors (including adipokines and cytokines). We have also begun to assess bioactive food components that target aspects of the insulin/IGF-1 signaling pathway and inflammatory pathways, as cancer prevention strategies in our tumor models.

Obesity is an important risk factor for several human cancers, and the prevention of obesity by CR, physical activity, and related interventions in animal models suppresses tumor development and extends lifespan. We are currently testing the hypothesis that the anticancer and antiaging effects of CR and exercise are mediated by reduced levels of IGF-1/insulin resistance and inflammation. Using oligonucleotide microarrays, kinase arrays and other molecular approaches, we are evaluating the molecular changes in adipose tissue, epithelial target tissues and tumors in response to CR and exercise with and without modulation of IGF-1, insulin resistance and or inflammatory responses. In addition, we are comparing other energy balance-modulating interventions, such as diet-induced obesity and phytochemicals, to determine the key pathways linking energy balance and carcinogenesis.

In collaboration with colleagues in the Laboratory of Tumor Immunology and Biology at the NCI, and the San Antonio Cancer Institute, we are testing the hypothesis that dietary or chemopreventive interventions such as CR, exercise, phytonutrients, or specific inhibitors of the cyclooxygenase and Akt/mTOR pathways can be used in combination with cancer vaccines to enhance the immune response and reduce tumorigenesis relative to the vaccine or the nutritional regimen alone. We are also collaborating with colleagues in the Department of Epidemiology at MD Anderson and the San Antonio Cancer Institute to evaluate the pre-clinical effects of breast cancer chemopreventive agents including tamoxifen, raloxifene and aromatase inhibitors in combination with dietary or physical activity interventions.