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James T. Stivers

James T. Stivers

Department Affiliation: Primary: Pharmacology and Molecular Sciences;
Secondary: Oncology
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 role of dNTP pool levels in cancer therapy and innate immunity against viruses.  We are also interested in fundamental problems in DNA damage recognition and repair and the design of small molecule inhibitors against DNA repair enzyme targets.  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:

  • Hansen, E.C., Seamon, K.J., Cravens, S.L., Stivers, J.T.  GTP Activator and dNTP Substrates of HIV-1 Restriction Factor SAMHD1 Generate a Long-lived Activated State. Proc Natl Acad Sci USA 111:E1843-51, 2014.  Pub Med Reference
     
  • Weil, A.F., Ghosh, D., Zhoub, Y., Seiple, L., McMahon, M.A., Spivak, A.M., Siliciano, R.F. and Stivers, J.T.  Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration. Proc Natl Acad Sci USA 110: E448-57, 2013. Pub Med Reference
     
  • Nabel, C.S., Jia, H., Ye, Y., Shen, Y., Goldschmidt, H.L., Stivers, J.T., Zhang, Y. and Kohli, R.M.  AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nature Chem Biol. 8: 751-758, 2012. Pub Med Reference
     
  • Schonhoft, J.D. and Stivers, J.T.  Timing facilitated site transfer of an enzyme on DNA. Nature Chem Biol. 8: 205-210, 2012. 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
     
  • 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
     
  • 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 Biol. 5: 407-13, 2009. 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
     
  • 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
     
  • 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

 


Other graduate programs in which Dr. Stivers participates:

BCMB Program
Chemistry-Biology Interface Program (CBI)
Program in Molecular and Computational Biophysics (PMCB)

 
 
 
 
 
 

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