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case western reserve university

BIOCHEMISTRY
 
 
Sedwick

Dr. David Sedwick

Associate Professor

Pub Med:

Dr. Dr. David Sedwick

The research program in Dr. Sedwick's laboratory focuses on defining the mechanisms of genotoxic damage induced by therapeutic agents and environmental mutagens.

Specific foci are on doxorubicin, antifolates, BCNU, X-radiation and radon. Over the past several years, base-line mutation analyses of all of these agents have been carried out, and mechanisms underlying specificity of these reactions have been elucidated.

Successful attempts to construct a transportable vector system for study of deletion mutations has been a highlight of the recent work in this area. These vectors are currently being used to determine how mutagens can lead to deletions of DNA in DNA seq uence-dependent reactions. Another highlight of work from Dr. Sedwick's laboratory has been the establishment of a fruitful collaboration with investigators at CWRU and other institutions on studies of the impact of mutator defects in colon cancer cells which appear to be responsible for an increased rate of cancer development among a subset of these patients. A direct correlation in these patients between high rates of mutation and defects in mismatch repair genes has been suggested by these studies. Current investigations are directed toward defining the mechanisms of mutation caused by these mutator defects.

 

Selected References

  • R.D. Anderson, M.L. Veigl, J. Baxter and W.D. Sedwick. Excision repair reduces doxorubicin-induced genotoxicity. Mutation Research 294, 215-222. (1993)

  • R.D. Anderson, C.Y. Bao, D.T. Minnick, J. Baxter, M.L. Veigl and W.D. Sedwick. Sequencing of double-stranded polymerase chain reaction products for mutation analysis. Mutation Resarch 288, 181-185. (1993)

  • D.T. Minnick, S.L. Gerson, L.L. Dumenco, M.L. Veigl and W.D. Sedwick. Specificity of bischloroethylnitrosourea-induced mutation in a Chinese hamster ovary cell line transformed to express human O6-alkylguanine-DNA alkyl transferase. Cancer Research 53, 997-1003. (1993.