Title:

Associate Professor

Education
Furman University, Master of Science, 1992
University College London, Doctor of Philosophy, 1996
Harvard School of Public Health, Postdoctoral Fellow, 1999

Description of Research Program
My long-term research goals are to utilize chemical/mechanistic approaches to understand biological systems that have a direct impact on human health and disease. DNA repair systems maintain the stability of our genomes by correcting DNA that has been damaged by normal cellular processes, carcinogens, and, ironically, most cancer chemotherapeutics. The laboratory is focused on understanding the Base Excision Repair (BER) pathway, which is responsible for correcting a wide variety of incorrect or damaged bases. One area of focus examines the mechanism of substrate recognition of DNA glycosylases, which initiate BER. A second area of focus examines how BER influences the cellular response to chemotherapy that can induce DNA damage. The goal is to expose cancer cells to the toxic effect of anticancer drugs, while protecting healthy cells. This area of focus also examines the crosstalk between BER and recombinational repair. Lastly, the laboratory has an interest in evaluating the interactions of nanoparticles with living cells. Nanoparticles have great potential to enable new technologies across many fields, from engineering to medicine. However, nanoparticles, like any other newly-emerging technology, can produce unintended consequences to its users or producers. Research in this regard will provide a better understanding of the surface chemistry of nanoparticles, which will in turn provide more accurate predictions on how nanoparticles interact with human cells and might cause toxicity.

Selected Publications

Wyatt, M.D. and Pittman, D.L. (2006). Methylating agents and DNA repair responses: methylated bases and sources of strand breaks.
Chemical Research in Toxicology, 19, 1580-1594.
This review was featured on the cover of the December issue.

Sen, S., Paraggio, N.A., Gearheart, L.A., Connor, E.E., Issa, A., Robert S. Coleman, Wilson, D.M. 3rd, Wyatt, M.D., Berg, M.A. (2005).
Effect of Protein Binding on Ultrafast DNA Dynamics: Characterization and Measurement of a Complex with APE1. Biophysical
Journal, 89, 4129-4138.

Li L., Connor, E.E., Berger, S.H., Wyatt, M.D. (2005). Determination of apoptosis, uracil incorporation, DNA strand breaks, and sister
chromatid exchanges under conditions of thymidylate deprivation in a model of BER deficiency. Biochemical Pharmacology. 70,
1458-1468.

Connor, E.E., Mwamuka, J., Gole, A., Murphy, C.J., Wyatt, M.D. (2005). Gold nanoparticles are taken up by human cells but do not
cause cytotoxicity. Small , 1, 325-327.

Connor, E.E., Wilson, J., Wyatt, M.D. (2005). The effects of substrate specificity on initiating the base excision repair of N-
methylpurines by variant human 3-methyladenine DNA glycosylases. Chemical Research in Toxicology, 18, 87-94.

Hitchcock, T.M., Dong, L., Connor, E.E., Meira, L.B., Samson, L.D., Wyatt, M.D., Cao, W. (2004). Oxanine DNA glycosylase activity
from mammalian alkyladenine glycosylase. Journal of Biological Chemistry, 279, 38177-38183.

Li L., Berger, S.H., Wyatt, M.D. (2004). Involvement of Base Excision Repair in Response to Therapy Targeted at Thymidylate
Synthase. Molecular Cancer Therapeutics, 6, 747-753.

Connor, E.E. and Wyatt, M.D. (2002). Active site clashes prevent the human 3-methyladenine DNA glycsosylase from improperly
removing bases. Chemistry & Biology,9, 1033-1041.

Lau, A., Wyatt, M.D., Glassner, B., Samson, L.D., Ellenberger, T. (2000). Molecular basis for discriminating between normal and
damaged bases by the human alkyladenine glycosylase, AAG. Proc. Natl. Acad. Sci. USA, 97, 13573-13578.

Wyatt, M.D. and Samson, L.D. (2000). The influence of DNA structure on hypoxanthine and 1, N6 ethenoadenine release by murine 3-
methyladenine DNA glycosylase. Carcinogenesis, 21, 901-908.

Wyatt, M.D., Allan, J.M., Lau, A., Ellenberger, T., Samson, L.D. (1999) 3-Methyladenine DNA glycosylases: structure, function and biological importance. BioEssays, 21, 668-676.

Allan, J.M., Engelward, B.P., Dreslin, J.A., Wyatt, M.D., Tomasz, M., Samson, L.D. (1998). Mammalian 3-methyladenine DNA glycosylase protects against the toxicity and clastogenicity of certain chemotherapeutic DNA cross-linking agents. Cancer Res., 58, 3965-3973.

Engelward, B.P., Weeda, G., Wyatt, M.D., Broekhof, J.L.M., de Wit, J., Donker, I., Allan, J.M., Gold, B., Hoeijmakers, J.H.J., Samson,

L.D. (1997). Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase. Proc. Natl. Acad. Sci. USA, 94, 13027­13033.

Wyatt, M.D., Lee, M., and Hartley, J.A. (1997). Alkylation specificity of a series of distamycin analogues that tether chlorambucil. Anticancer Drug Des. ,12, 49-60.

Wyatt, M.D., Lee, M., and Hartley, J.A. (1997). Sequence specificity of alkylation for a series of benzoic acid mustard and imidazole-containing analogues of distamycin. The importance of local DNA sequence conformation. Nucleic Acids Res.25, 2359-2364.

Wyatt, M.D., Lee, M., Garbiras, B.J., Souhami, R.L., Hartley, J.A. (1995). Sequence specificity of alkylation for a series of nitrogen mustard containing analogues of distamycin of increasing binding site size: evidence for increased cytotoxicity with enhanced sequence specificity. Biochemistry ,34, 13034-13041.

Broggini, M., Coley, H., Mongelli, N., Pasenti, E., Wyatt, M.D., Hartley, J.A., D’Incalci, M. (1995). DNA sequence-specific adenine alkylation by the novel antitumor drug tallimustine (FCE 24517), a benzoyl nitrogen mustard derivative of distamycin. Nucleic Acids Res., 23, 81-87.

Wyatt, M.D., Garbiras, B.J., Haskell, M.K., Lee, M., Souhami, R.L., Hartley, J.A. (1994). Structure-activity relationship of a series of nitrogen mustard- and pyrrole-containing minor groove-binding agents related to distamycin. Anticancer Drug Des. 9, 511-525.

Wyatt, M.D., Garbiras, B.J., Lee, M., Forrow, S.M., Hartley, J.A. (1994). Synthesis and DNA binding properties of a series of N to C linked and imidazole containing analogues of distamycin. Bioorg. Med. Chem. Lett. 4, 801-806.