Phone
608-265-5204
Education:
- Ph.D., Yale University, (1994)
- Postdoctoral Research: Baylor College of Medicine
- Somatostatin Receptor Type 2 and Thyroid-Stimulating Hormone Receptor Expression in Oncocytic Thyroid Neoplasms: Implications for Prognosis and Treatment
- Living high - training low model applied to C57BL/6J mice: Effects on physiological parameters related to aerobic fitness and acid-base balance
- SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction
- Aerobic training associated with an active lifestyle exerts a protective effect against oxidative damage in hypothalamus and liver: The involvement of energy metabolism
- Retraction Note to: Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice
- Establishment of Quantitative PCR Assays for Active Long Interspersed Nuclear Element-1 Subfamilies in Mice and Applications to the Analysis of Aging-Associated Retrotransposition
- A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in <em>C. elegans</em>
- Prematurely aging mitochondrial DNA mutator mice display subchondral osteopenia and chondrocyte hypertrophy without further osteoarthritis features
- Housing conditions modulate spontaneous physical activity, feeding behavior, aerobic running capacity and adiposity in C57BL/6J mice
- The effects of AICAR and rapamycin on mitochondrial function in immortalized mitochondrial DNA mutator murine embryonic fibroblasts
My research program is focused on understanding the molecular basis of the aging process and its retardation by caloric restriction. Our studies have uncovered a central role for mitochondria and energy metabolism in both aging and its retardation by caloric restriction. We use the mouse as model system and most of our studies are based on the construction of mouse models of accelerated or retarded aging. We generate these models through the use of gene targeting in ES cells, as well as transgenic animal construction. An example of such work from our Laboratory is a widely used model of age-related mitochondrial dysfunction, mice deficient in the exonuclease domain of the mitochondrial DNA polymerase gamma (PolgD257A).
We have previously used DNA microarrays to shown that caloric restriction leads to a “metabolic reprogramming” at the transcriptional level. Our more recent studies have focused on the role of the sirtuin SIRT3 in mediating the beneficial effects of caloric restriction in aging, including such metabolic reprogramming. SIRT3 is a NAD+ dependent deacetylase located in the mitochondrial matrix that induces metabolic shifts in response to caloric restriction. Such metabolic shifts appear to increase oxidative stress resistance and prevent an increase in age-related apoptosis. We are investigating if this metabolic adaptation underlies the beneficial effects of caloric restriction in age-related diseases as well as age-related physiological declines. The long-term goal of our studies is to identify critical pathways in aging and find either natural or synthetic compounds that modulate such pathways in a favorable manner.