Professor, Pharmacology and Toxicology
To maintain the genomic integrity of the organism, individual cells within the organism must make appropriate life and death decisions. Ongoing research is aimed at understanding the molecular mechanisms by which cells respond to toxic chemicals and radiation by activating pathways that lead to repair of damage and cell recovery or to cell death by apoptosis or necrosis. The information gained is used toward the design of therapeutic strategies for the treatment of diseases in which cells are either inappropriately resistant to cell death (cancer) or inappropriately sensitive to cell death (heart attack, stroke, etc.).
The laboratory is studying the involvement of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG) in the responses of cells to potentially toxic conditions. PARPs and PARG catalyze the opposing arms of ADP-ribose polymer cycles involved in alternative responses to nuclear damage. These include the repair of nuclear DNA and protein damage, pathways leading to programmed cell death (apoptosis), and pathways leading to cell death by necrosis. ADP-ribose polymer cycles are also involved in the maintenance of the telomere structures that protect the ends of chromosomes.
The laboratory uses a structure-based approach for characterization of its molecular targets. Techniques routinely used in the laboratory include protein isolation and microsequencing, cDNA cloning, heterologous protein expression and characterization, site-directed mutagenesis, expression and characterization of dominant negative proteins in cultured cells, and the use of transgenic animals.
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