The lab is interested in the DNA damage response pathway, which is critical for maintaining genomic stability. Dysfunction of this pathway results in genomic instability and cancer predisposition. Therfore, many components of the DNA damage response pawhway are identified as tumor suppressors.

Similar to mitogenic signaling pathways, the DNA damage-induced signaling pathway consists of kinase-dependent signaling cascades that regulate cell cycle progression, DNA repair and apoptosis following DNA damage, collectively called the DNA damage response pathwat. ATM (ataxia telangiectasia mutated protein) and ATR (ataxia telangiectasia-related protein), two phosphatidylinositol 3-kinase-related protein kinases, are upstream kinases in this DNA damage response pathway. ATM and ATR activate the downstream checkpoint kinases Chk1 and Chk2/Cds1. These four protein kinases, with the help of mediator proteins (MDC1, 53BP1) phosphorylate a number of downstream effector proteins, including tumor suppressors p53 and BRCA1, where they coordinate DNA repair, cell cycle progression, transcriptional regulation and apoptosis in response to various DNA-damaging events. By focusing on several key regulators (ATM, MDC1, Chk2 and BRCA1) in this pathway and using biochemical and genetic approaches, we attempt to elucidate the roles of this DNA damage pathway in tumorigenesis.

The lab is also interested in molecular mechanism of aging. Sir2 family protein deacetylases has been shown to regulate longevity in multiple organisms. Overexpression or activation of Sir2 results in extended life span in yeast, c.elegant and drosophila. We are investigating in the cellular function and regulation of the mammalian ortholog of Sir2, SirT1, using biochemical and geneti apporaches.

I am a member of the Mayo Clinic Cancer Center.