Structure-function studies of nucleotide excision repair proteins
Structure-function Studies of Nucleotide Excision Repair Proteins.
Faulty DNA repair can promote mutations, aging, cancer and cell death. The process by which protein components of repair detect damaged or modified bases within DNA is an important but poorly understood type of protein-DNA interaction. The cell contains a series of pathways designed to protect its DNA from environmental and endogenous damage. One of the most remarkable aspects of nucleotide excision repair (NER) is that it can remove a wide range of DNA lesions that differ in chemistry and structure. We are studying the structure, function and dynamics of bacterial NER proteins using a variety of approaches, including single-molecule techniques using Atomic Force microscopy, and TIRF microscopy. We seek to understand the structural motifs which these proteins use to recognize DNA damage and how these repair proteins sort through a sea of nondamaged DNA to find altered nucleotides.
Mitochondria and Disease:
Our group is testing the hypothesis that ROS generated in the mitochondria results in mtDNA damage causing a vicious cycle of damage: mtDNA damage causes a decrease in transcription and loss of essential mitochondrial proteins, causing a inhibition of electron transport and subsequent release in more ROS. This process causes further mitochondrial decline and many degenerative diseases associated with aging. We have developed a very sensitive DNA damage assay based on quantitative PCR that allows us to examine damage to nuclear and mitochondrial DNA from as little as 100 microliters of human blood. We are currently examining the role of mtDNA damage and repair in several human diseases including cancer and Friedreichâ€™s ataxia. Finally, we are assessing the bioenergetics of cancer cells by measuring oxidative phosphorylation and glycolysis.
PhD 1984, Oak Ridge Graduate School of Biomedical Sciences, University of Tennessee
1984-1988, Lineberger Cancer Research Center, University of North Carolina
Department of Pharmacology & Chemical Biology
University of Pittsburgh
Hillman Cancer Center
5117 Centre Avenue
Research Pavilion, Suite 2.6
Pittsburgh, PA 15213-1863