Alex Drohat, Ph.D. Assistant Professor      108 N. Greene St.      Baltimore, MD 21201      Phone: 410-706-8118      Fax: 410-706-8297      email: adroh001@umaryland.edu EDUCATION 1988     B.S., Aerospace Engineering, University of Maryland             College Park 1997     Ph.D., Biochemistry and Molecular Biology, University of              Maryland Baltimore POST GRADUATE EXPERIENCE 1998-2000   National Research Council Postdoctoral Fellow, Center                   for Advanced Research in Biotechnology (CARB) of the                   University of Mary  land Biotechnology Institute and the                    National Institute of Standards and technology 2001-2002   Postdoctoral Fellow, Johns Hopkins                   University School of Medicine

PROFESSIONAL EXPERIENCE
Faculty Appointments
2002-2005       Assistant Professor of Biomedical Sciences, University at Albany, SUNY
2005–present   Assistant Professor of Biochemistry and Molecular Biology, University of Maryland Baltimore

Other Positions
1988-1993       Engineer, Aviation Life Support and Survival Equipment Branch, Naval Air Systems Command, 
                      Washington, DC.
1993-1998       Research Assistant and PhD candidate, Dept. of Biochemistry & Molecular Biology, University of 
                      Maryland Baltimore
2002-2005       Research Scientist (PI), Wadsworth Center, New York State Department of Health, Albany NY

RESEARCH DESCRIPTION

We use NMR spectroscopy and a variety of other biophysical, biochemical, and molecular biological approaches to determine the structure and elucidate mechanism of DNA repair enzymes. The reactive nucleobases of DNA are continuously damaged (chemically modified) by cellular metabolites and exogenous agents, producing cytotoxic and/or mutagenic lesions that play a role in the development of disease and in ageing. Counteracting this inevitable threat is the base excision repair (BER) pathway, initiated by a damage-specific DNA glycosylase. Using a base-flipping mechanism, these enzymes find and remove damaged and mismatched bases in the vast expanse of normal DNA. While some DNA glycosylases exhibit significant catalytic power, they are perhaps more impressive for their extraordinary specificity for certain lesions and against normal bases. Some DNA glycosylases recognize a single lesion, whereas others are more permissive and can remove multiple forms of damage. We are studying two human DNA glycosylases that are specific for G/T and G/U mispairs in addition to numerous other lesions. A central question we are addressing is how these enzymes achieve specificity for a broad range of lesions while avoiding normal bases. We are also investigating the general question of how the activity of DNA glycosylases is stimulated by AP endonuclease, the follow-on enzyme in BER, i.e. how are the first two steps of BER coupled? Finally, we are interested in characterizing and understanding the biological role of protein-protein interactions among BER enzymes, and involving BER enzymes and proteins from other pathways.

SELECTED PUBLICATIONS
Cao, C., Kwon, K., Jiang, Y.L., Drohat, A.C., and Stivers, J.T. (2003) “Solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3-methyladenine DNA glycosylase I” J. Biol. Chem. 278: 48012-48020.

Jiang, Y.L., Drohat, A.C., Ichikawa, Y., and Stivers, J.T. (2002) “Probing the Limits of Electrostatic Catalysis by Uracil DNA Glycosylase Using Transition-State Mimicry and Mutagenesis” J. Biol. Chem. 277: 15385-15392.

Drohat, A.C., Kwon, K., Krosky, D.L., and Stivers, J.T. (2002) “3‑methyladenine DNA Glycosylase I is an Unexpected Helix-Hairpin-Helix Superfamily Member” Nature Struct. Biol. 9: 659-664.

Drohat, A.C., and Stivers, J.T. (2000) "NMR Evidence for an Unusually Low N1 pKa for Uracil Bound to Uracil DNA Glycosylase: Implications for Catalysis" J. Am. Chem. Soc. 122: 1840-1841.

Drohat, A.C., and Stivers, J.T. (2000) "Escherichia coli Uracil DNAGlycosylase: NMR Characterization of the Short Hydrogen Bond from His187 to Uracil O2" Biochemistry 39: 11865-11875.