Dr. Wilson received a B.S. in Biochemistry from the University of Wisconsin in 1987. He went on to study the health sciences, with an emphasis on molecular biology and neuroscience, at Washington University in St. Louis. He received his M.D. and Ph. D. in 1994. He continued at Washington University pursuing postgraduate clinical training in Laboratory Medicine, with an emphasis on molecular diagnostics, and research training in DNA repair as a Howard Hughes postdoctoral fellow in the laboratory of Dr. Michael Lieber. He joined the faculty at the University of Michigan as an Assistant Professor and Biological Sciences Scholar in 1999.
Mutagenesis, DNA repair, chromosomal dynamics
The goal of our laboratory is to gain insight into the molecular basis of chromosomal rearrangement in cancer and the germline by systematically identifying both enzymatic and structural components of the DNA double-strand break (DSB) repair mechanisms, and characterizing how these (and deficiencies therein) interact to achieve the sequence of events resulting in repair (or rearrangement). This is done in part using novel assays developed in the genetically tractable model organism Saccharomyces cerevisiae, since it is clear that the fundamental mechanisms of DSB repair are preserved in all eukaryotes. Specific factors under study include non-homologous end joining (NHEJ) enzymes such as polymerases, nucleases and especially the critical enzyme DNA ligase IV. Questions center on the structural and biochemical features of these enzymes that allow them to uniquely participate in NHEJ, addressed using a combination of genetic and biochemical repair assays. Other factors of interest are the structural Ku and Mre11-Rad50 complexes. Here, questions center on the nature and assembly of the overall repair complex, addressed using a combination of protein interaction and chromatin immunoprecipitation approaches. Our ultimate goal is to correlate findings from the above approaches to genome stability in mammalian cells. This is being achieved by high-throughput genomic approaches in which spontaneous and induced structural changes of chromosomes are correlated to the status of the DSB repair machinery. These last efforts have led to a substantial bioinformatics focus in recent years that is additionally being extended to the study of transcriptional responses to DNA damage stress.