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overview The research I pursue is focused on DNA replication and seeks to provide fundamental insights into how these mechanisms are related to human health, especially cancer. I have expertise in a number of areas pertinent to the current application including: biochemical/biophysical analysis of enzymes, structural biology (X-ray crystallography and molecular modeling techniques), mass spectrometry and genomic instability in cancer. In addition to in silico modeling approaches, I have been involved in solving thirty-four crystal structures submitted to the Protein Data Bank. I am first author on seventeen of these PDB submissions, and my laboratory has solved five crystal structures since I joined the faculty at UAMS. I have an active collaboration (General users proposal, GUP-41183) with the Northeastern collaborative access team (NE-CAT) at the Advanced Photon Source (APS) that grants us access to the 24-ID-E and 24-ID-C beamlines for data collection. The research I pursue is focused on DNA damage tolerance pathways and seeks to provide fundamental insights into how these mechanisms function under basal conditions and how they go astray during tumorigenesis or as a function of age. I have received funding from the National Institutes of Health in the form of an R00 award (GM084460) and a R01 (CA183895). I have established a strong research program with two senior post-doctoral fellows and three Ph.D. students. In less than four years, my team has published nine full, peer-reviewed research articles on which I am corresponding author. Work from my group has recently culminated in a manuscript that reveals important and previously unrecognized properties related to Werner’s syndrome protein (WRN) modulation of polymerase activity during bypass of oxidative DNA damage. Experiments from my group illustrate that WRN has a strong impact on the DNA adduct bypass properties of human DNA polymerases (pols) eta and kappa, inducing more accurate synthesis across oxidative damage (published in The Journal of Biological Chemistry and Nucleic Acids Research). Another study from my laboratory that was conducted in collaboration with Prof. Peter Crooks (UAMS) identified novel small-molecule inhibitors of the replication stress response enzyme human DNA polymerase eta, with the resulting manuscript recently being published in ACS Chemical Biology. We continue to pursue projects related to translesion polymerase activity in cancer and are actively developing new TLS pol inhibitors as a way to sensitize tumors to genotoxic anti-cancer drugs (e.g. cisplatin, doxorubicin). My long-term goal is to contribute in a meaningful fashion to the scientific endeavors that seek to improve human health, our ability to treat disease & our fundamental understanding of living systems.

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