Department Affiliation: Primary: Pharmacology and Molecular Sciences
Degree: Ph.D., Johns Hopkins University
Rank: Professor
Telephone Number: 410-502-2758
Fax Number: 410-955-3023
E-mail address: jstivers@jhmi.edu
Home Page: Stivers
School of Medicine Address: Room 314 Wood Basic Science Building, 725 N. Wolfe Street, Baltimore, MD 21205
Molecular Mechanism and Inhibition of Enzymes Involved in DNA and RNA Metabolism
- Mechanism and Structure of DNA Repair Enzymes
- NMR and Biophysical Studies of Topoisomerase IB
- Chemical and Dynamic Properties of Enzymes Using Heteronuclear NMR
- Structures of Enzymatic and Non-Enzymatic Transition-States
- Rational Design of Inhibitors and Chemical Probes for Protein-DNA Interactions
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 energetics 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 and in acquired immunity.
Representative Publications:
- Krosky, D.J., Bianchet M.A., Seiple, L., Chung, S., Amzel, L.M., and Stivers, J.T. (2006) Mimicking Damaged DNA with a Small Molecule Inhibitor of Human UNG2, Nucleic Acids Res 30, 5872-5879. Pub Med Reference
- Seiple, L., Jaruga, P. Dizdaroglu, M., and Stivers, J. T. (2006) Linking Uracil Base Excision Repair and 5-Fluorouracil Toxicity in Yeast, Nucleic Acids Res. 30, 140-151. Pub Med Reference
- Nagarajan, R. and Stivers. J.T. (2007) Unmasking Anticooperative DNA Binding Interactions of Vaccinia DNA Topoisomerase I, Biochemistry 46, 192-199. Pub Med Reference
- Parker, J. B., Bianchet, M. A., Krosky, D. J., Friedman, J. I., Amzel, L. M. and Stivers, J. T. (2007) Enzymatic Capture of an Extrahelical Thymine in the Search for Uracil in DNA, Nature 449, 433-438. Pub Med Reference
- Stivers, J.T. (2008) Extrahelical Damaged Base Recognition by DNA Glycosylase Enzymes, Chemistry 14, 786-793.Pub Med Reference
- Seiple, L. A. Cardellina, J. H. Akee, R. and Stivers J. T. (2008) Potent Inhibition of Human AP Endonuclease 1 by Arylstibonic Acids. Mol Pharmacol 73, 669-677. Pub Med Reference
- Kim, H., Cardellina, J. H. II, Akee, R., Champoux, J. J. and Stivers, J. T. (2008) Arylstibonic Acids: Novel Inhibitors and Activators of Human Topoisomerase IB, Bioorg Chem 36, 190-197. Pub Med Reference
- Porecha, R. H., and Stivers, J.T. (2008) Uracil DNA Glycosylase Uses DNA Hopping and Short-Range Sliding to Trap Extrahelical Uracils, Proc Natl Acad Sci USA in press.
- Parker, J. B. and Stivers, J.T. (2008) Uracil DNA Glycosylase: Revisiting Substrate-Assisted Catalysis by DNA Phosphate Anions, Biochemistry, in press.
Other graduate programs in which Dr. Stivers participates:
BCMB Program
Anti-Cancer Drug Development Program
Chemistry-Biology Interface Program (CBI)
Program in Molecular and Computational Biophysics (PMCB)
