Current Research Projects:
Most of the work in my lab focuses on SirT1, an NAD+-dependent protein deacetylase with more than 80 known substrates. SirT1 also binds large numbers of other proteins through its intrinsically unstructured N and C termini and is a hub in a scale-free network of nuclear proteins that also includes many of the most important regulators of gene expression, cell growth and differentiation (p53, p300, NF-κB, Rb, etc). To investigate the role of SirT1 in animal aging and physiology, we have created mouse strains carrying mutations in the sirt1 gene that ablate protein expression, render the protein catalytically inactive, or render the activity reversibly inducible. Our results suggest that SirT1 is important in facilitating adaptation to nutritional stress (calorie restriction or high calorie diets) and other stresses such as hypoxia. SirT1 does not appear to have a direct influence on oncogenesis but may indirectly influence cancer development by playing an important role in immune surveillance.

Keywords: sirt1, knockout mice, aging, stem cells, gene expression