Professor
Department of Pharmacology and Molecular Sciences
School of Medicine

jstivers@jhmi.edu

314 WBSB
725 N. Wolfe Street
Baltimore, MD 21205

Office: 410-502-2758
Lab: 410-614-9644

Our laboratory focuses on the general problem of specific molecular recognition in biological systems. Our work begins with structure, but we are very interested in pushing and extending the measurement envelope so that we obtain a fundamental understanding of the energetic basis for molecular recognition. Accordingly, we use a wide breadth of molecular, genetic and biophysical approaches that together shed light on aspects of molecular recognition that are not apparent from structural studies alone. Our long range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and viral pathogenesis.

Selected Publications
Kohli, R.M., S.R. Abrams, K.S. Gajula, R.W. Maul, P.J. Gearhart, and J.T. Stivers. (2009) A portable hotspot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase. J. Biol. Chem. 284:22898-22904.

Friedman, J.I., A. Majumdar, and J.T. Stivers. (2009) Nontarget DNA binding shapes the dynamic landscape for enzymatic recognition of DNA damage. Nucleic Acids Res. 37:3493-3500.

Chung, S., J.B. Parker, M. Bianchet, L.M. Amzel, and J.T. Stivers. (2009) Impact of linker strain and flexibility in the design of a fragment-based inhibitor. Nature Chem. Biol. 5:407-413.

Porecha, R.H., and J.T. Stivers. (2008) Uracil DNA glycosylase uses DNA hopping and short-range sliding to trap extrahelical uracils. Proc. Natl. Acad. Sci. USA 105:10791-10796.

Parker, J.B., M.A. Bianchet, D.J. Krosky, J.I. Friedman, L.M. Amzel, and J.T. Stivers. (2007) Enzymatic capture of a transient extrahelical thymine in the search for uracil in DNA. Nature 449:433-437.

Nagarajan, R., and J.T. Stivers. (2007) Unmasking anticooperative DNA binding Interactions of vaccinia DNA topoisomerase I. Biochemistry 46:192-199.

Krosky, D.J., M.A. Bianchet, L. Seiple, S. Chung, L.M. Amzel, and J.T. Stivers. (2006) Mimicking damaged DNA with a small molecule inhibitor of human UNG2. Nucleic Acids Res. 30:5872-5879.

Cao, C., Y.L. Jiang, F. Song, and J.T. Stivers. (2004) Dynamic opening of DNA during the enzymatic search for a damaged base. Nat. Struct. Mol. Biol. 11:1230-1236.

Cao, C., K. Kwon, Y.L. Jiang, A.C. Drohat, and J.T. Stivers. (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.