EducationB.S., University of Wisconsin at Platteville, 1964
Ph.D., Marquette University, 1970
ResearchThe research interests of our laboratory are focused in two areas: 1) the mitochondrial proteomics of aging and 2) the investigation of the mechanisms of action the transcription co-activator PGC-1α which has a broad range of actions including stimulation of mitochondrial biogenesis, brown fat thermogenesis and hepatic gluconeogenesis. Over-expression of PGC-1α appears to have anti-aging effects mimicking the actions of caloric restriction.
The transcriptional co-activator, peroxisome proliferator-activated receptor-γ (PPAR-γ) co-activator -1α (PGC-1α) is thought to integrate the molecular regulatory circuitry involved in the transcriptional control of cellular energy metabolism, including mitochondrial function and biogenesis. We have developed a unique transgenic mouse model that over-expresses PGC-1α. Mitochondria have been proposed to be an important link between the age-related accumulation of oxidative damage caused by reactive oxygen species and the alterations of physiological function associated with aging. One of the major actions of PGC-1α is the induction of mitochondrial biogenesis. Our long-term objectives are to determine if over-expression of PGC-1α extends life span of the transgenic animal and, if so, to then determine a mechanism of action for that effect. In addition, we have discovered that the PGC-1α transgenic animals exhibit increased skeletal muscle insulin sensitivity. Insulin sensitivity is known to decline with age and, in addition, insulin resistance is one of the earliest symptoms to appear in the development of Type II diabetes mellitus, an age-related disease. Another long-term objective is to determine the mechanism of action of PGC-1α with regard to insulin sensitivity. This may lead to the development of a pharmacological approach to slow or prevent the onset of this disease.