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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

 

Uracil Metabolism and Applications to Cancer Therapy, Viral Pathogenesis, Acquired and Innate Immunity.

My laboratory is broadly interested in the biology of the RNA base uracil when it is present in DNA.  Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. Accordingly, we use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. 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 HIV-1 pathogenesis.

 

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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