Department of Pharmacology and Molecular Sciences
School of Medicine
B.S. 1987,University of Washington, Seattle
Ph.D. 1993, Johns Hopkins University
725 N. Wolfe Street
Baltimore, MD 21205
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.
Rowland, M., J.D. Schonhoft, J.T. Stivers. (2014) Microscopic Mechanisim of DNA Damage Searching by hOGG1. Nucleic Acids Res. (in press)
Seamon, K.J., E.C. Hansen, A. Kadina, B. Kashemirov, C. McKenna, N. Bumpus, and J.T. Stivers. (2014) Small Molecule Inhibition of SAMHD1 dNTPase Through Tetramer Destabilization. J. Am. Chem. Soc. 136:9822-9825.
Hansen, E.C., K.J. Seamon, S.L. Cravens, and J.T. Stivers. (2014) GTP Activator and dNTP Substrates of HIV-1 Restriction Factor SAMHD1 Generate a Long-lived Activated State. Proc. Natl. Acad. Sci. USA. 111: E1843-1851.
Weil, A.F., D. Ghosh, Y. Zhoub, L. Seiple, M.A. McMahon, A.M. Spivak, R.F. Siliciano, and J.T. Stivers. (2013) Uracil DNA Glycosylase Initiates Degradation of HIV-1 cDNA Containing Misincorporated dUTP and Prevents Viral Integration. Proc. Natl. Acad. Sci. USA. 110:E448-457.
Nabel, C.S., H. Jia, Y. Ye, Y. Shen, H.L. Goldschmidt, J.T. Stivers, Y. Zhang, and R.M. Kohli. (2011) AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nature Chem. Biol. 8:751-758.
Ye, Y., M. Stahley, J. Xu, J. Friedman, Y. Sun, J. McKnight, J. Gray, G. Bowman, and J.T. Stivers. (2012) Enzymatic excision of uracil residues in nucleosomes depends on local DNA structure and dynamics. Biochemistry. 51:6028-6038.
Schonhoft, J.D., and J.T. Stivers. (2012) Timing facilitated site transfer of an enzyme on DNA. Nature Chem. Biol. 8:205-210.
Friedman, J.I., M.T. McMahon, J.T. Stivers, and P.C.M. van Zijl. (2010) Indirect detection of labile solute proton spectra via the water signal using frequency-labeled exchange (FLEX) transfer. J. Am. Chem. Soc. 132:1813-1815.
Sun, Y., J.I. Friedman and J.T. Stivers. (2011) Cosolute Paramagnetic Relaxation Enhancements Detect Transient Conformations of Human Uracil DNA Glycosylase (hUNG). Biochemistry. 50:10724-10731.
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.