UMGCC Research Program:
Molecular and Structural Biology Program
Education/Training:
College Degree:
B.A.,Southern Illinois University
Post Doctoral
Degree:
Ph.D., Loyola University, Chicago
Fellowship:
Thomas Jefferson University
Contact
Information:
Mailing Address:
655 W. Baltimore St
Rm. 6-015
Baltimore, MD 21201
Email:
twilson@som.umaryland.edu
Phone:
410-706-3086
Fax:
410-706-6138
Research Interests:
My research focuses on the biochemical characterization of the human DNA mismatch repair (MMR) pathway. Instability of simple repetitive sequences in DNA (microsatellite instability or MSI) is a hallmark of defects in MMR. The most widely held mechanism for MSI suggests that during the replication of simple repeat tracts, the nascent DNA strand may slip forming insertion/deletion loops (IDL) that would then result in the lengthening or shortening of these sequences if not repaired. This form of genetic instability is exhibited in the tumors of patients with hereditary nonpolyposis colorectal cancer (HNPCC). To date, mutations in five MMR genes, hMSH2, hMLH1, hPMS2, hMSH6, and hPMS1, have been correlated with HNPCC.
To order to investigate the MMR pathway, we perform biochemical, molecular, and cellular techniques. Three main projects are currently underway in the laboratory. First, we are examining the role(s) of the exonuclease, hEXO1, in the removal of DNA lesions. Of particular interest is determining the mechanism by which the hMSH2-hMSH3 and hMSH2-hMSH6 complexes functionally interact with hEXO1 and direct it to the site of the DNA lesion. Second, we are determining the functional consequences of HNPCC mutations on the activity of the MMR proteins. And third, we are examining the effect of environmental toxins on MMR activities.
Publications:
Wilson, T.M., Vaisman, A., Martomo, S.A., Sullivan, P., Lan, L., Hanaoka, F., Yasui, A., Woodgate, R., and Gearhart, P.J. (2005) MSH2-MSH6 stimulates DNA polymerase eta, suggesting a role in antibody hypermutation. J. Exp. Med., 201:637-645.
Bai, H., Jones, S., Guan, X., Wilson, T.M., Sampson, J.R., Cheadle, J.P., and Lu, A.-L. (2005) Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis. Nucleic Acids Res., 26:597-604.
Owen, B.A.L., Badger II, J.D., Yang, Z., Lai, M., Gajec, M., Hayes, J.J., and Edelman, W., Kucherlapati, R., Wilson, T.M., and Cynthia T. McMurray (2005) (CAG)(n)-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition. Nat. Struct. Mol. Biol. In Press.
Doherty, K.M., Sharma, S., Uzdilla, L., Wilson, T.M., Cui, S., Vindigni, A., Brosh, R.M. Jr., (2005) RECQ1 helicase interacts with human mismatch repair factors that regulate genetic recombination. J. Biol. Chem. In Press.
Patel, S.A., Kimos, M.C., Uzdilla, L.A., and Wilson, T.M. (2005) Cadmium Inhibits Multiple Steps of DNA Mismatch Repair. In revision.
