Personal Statement
My research interests are focused on the molecular mechanisms of DNA replication, repair, and recombination pathways that maintain genome stability. There are several compelling reasons for studying these processes. Firstly, abnormalities in these processes result in genome instability that in turn leads to increased cancer formation.
Secondly, because of the differences in these processes between normal and cancer cells, a better understanding of these processes and how they are altered in cancer cells will provide a framework for developing improved and novel cancer therapies.
Finally, there is mounting evidence that abnormalities in DNA repair are a causative factor in neurodegeneration. As a postdoctoral fellow in the laboratories of Stuart Linn and Tomas Lindahl, I received training in the purification and characterization of proteins involved in DNA replication, repair, and recombination.
Upon becoming an independent investigator, I expanded the range of experimental approaches to include molecular biology, gene cloning, yeast genetics, and structural biology. My lab has focused on delineating the cellular functions of eukaryotic DNA ligases that are key enzymes in DNA replication, repair, and recombination using a combination of in vitro and in vivo approaches. Specifically, we have identified DNA ligase-interacting proteins and characterized these interactions.
These studies have been continuously funded by the National Institutes of Health (NIH) for more than 20 years and resulted in more than 100 publications. During this time, I have mentored 2 M.S. students, 9 Ph.D. students, and 14 postdoctoral fellows. As a participant in a multi-institutional NCI P01 program project focused on the structural biology of DNA repair for more than 15 years, I have has greatly benefited from the collaborations fostered by this program.
In collaborative work with Dr. Tom Ellenberger, we have determined the atomic resolution structures of human DNA ligases I and III complexed with nicked DNA. This has enabled us to identify small molecule inhibitors using a structure-based approach. Notably, several of the ligase inhibitors preferentially sensitize cancer cells to DNA damage, and we are currently evaluating these lead compounds and their derivatives as potential therapeutic agents in mouse models of human cancer.
Before joining the University of New Mexico Comprehensive Cancer Center, I served as the Associate Director for Basic Research in the NCI-designated Cancer Centers at the University of Texas Health Science Center at San Antonio and the University of Maryland, as well being a research program leader. In addition, I was involved in the establishment of the Molecular Medicine Graduate Programs, serving as the graduate program director at both my former institutions as well as principal investigator of an NCI T32 grant focused on DNA repair and tumor suppressors at the University of Texas Health Science Center at San Antonio.
Since I have a well-funded research program that utilizes cutting-edge technologies in basic and translational research and extensive experience in the organization and administration of transdisciplinary research programs and NCI-designated cancer centers, I am well qualified to serve as the Associate Director for Basic Research in the University of New Mexico Comprehensive Cancer Center.
Education
Graduate School: University of Newcastle upon Tyne, England (1983), Biochemistry and Molecular Genetics