James T. Stivers

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 

Structural and Chemical Biology of Uracil Metabolism and Applications to Cancer Therapy, Innate and Adaptive Immunity.         

Our laboratory focuses on the general problem of specific molecular recognition in biological systems.   One major area of focus is the surprising role of the simple nucleobase uracil in cancer therapy, as well as innate and adaptive immune responses.  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 identify new drug targets, and design novel small molecules that could become starting points for new chemotherapy or antiviral drugs.  

Representative Publications:

• Parker, J. B., Bianchet, M. A., Krosky, D. J., Friedman, J. I., Amzel, L. M. and Stivers, J. T.  Enzymatic Capture of an Extrahelical Thymine in the Search for Uracil in DNA.  Nature 449:433-438, 2007. Pub Med Reference

• Porecha, R. H., and Stivers, J.T.  Uracil DNA Glycosylase Uses DNA Hopping and Short-Range Sliding to Trap Extrahelical Uracils.  Proc. Natl. Acad. Sci. USA 105:10791-10796, 2008. Pub Med Reference

• McMahon M.A., Siliciano JD, Lai J, Liu JO, Stivers J.T., Siliciano R.F., Kohli R.M.  The anti-herpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multi-drug resistance mutation. J Biol Chem. 283:31289-31293, 2008. (accelerated communication) Pub Med Reference

• Huang, H., Stivers, J.T., Greenberg, M.M.   Competitive inhibition of uracil DNA glycosylase by a modified nucleotide whose triphosphate is a substrate for DNA polymerase. J. Am. Chem. Soc., 131, 1344-1345, 2009. Pub Med Reference

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

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

• Kohli, R., Abrams, S., Gajula, K., Maul, R., Gearhart, P.,  Stivers, J.T.  A portable hotspot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase.  J. Biol. Chem. 284:22898-22904, 2009. Pub Med Reference 

• Kohli, R., Maul, R.W., Guminski, A., McClure, R.L., Gajula, K., Saribasak, H., McMahon, M., Siliciano, R.F., Gearhart, P., Stivers, J.T.  Local sequence targeting in the AID/APOBEC family differentially impacts retroviral restriction and antivody diversification.  J. Biol. Chem. 285:40956-40964, 2010. Pub Med Reference

• Grogan, B.C., Parker, J.B., Guminski, A.F., Stivers, J.T.  Effect of the Thymidylate Synthase Inhibitors on dUTP and TTP Pool Levels and the Activities of DNA Repair Glycosylases on Uracil and 5-Fluorouracil in DNA.  Biochemistry 50:618-627, 2011. Pub Med Reference

• Friedman, J.I., Jiang, Y.L., Miller, P.S., Stivers, J.T.  Unique Dynamic Properties of DNA Duplexes Containing Interstrand Cross-Links.  Biochemistry 50:882-890, 2011. Pub Med Reference

Other graduate programs in which Dr. Stivers participates:

Anti-Cancer Drug Development Program   
BCMB Program   
Chemistry-Biology Interface Program (CBI)   
Program in Molecular and Computational Biophysics (PMCB)