My laboratory is broadly interested in how dNTP pool levels and composition influence genetic stability, adaptive and innate immunity, inflammation, carcinogenesis, cellular senescence and aging. Current work in the lab focuses on two key aspects of dNTP metabolism. We are elucidating how the uniquely high concentration of dUTP in resting immune cells is used as a potent HIV-1 restriction factor in macrophages. We are also interested in the epigenetic effects of uracil when it is present in DNA. Our long-range goal is to design novel small molecules that predictably alter the make up of nucleotide pools in cells for antiviral, anticancer, and anti-inflammatory therapeutic uses.
Seamon KJ, Sun Z, Shlyakhtenko LS, Lyubchenko YL, Stivers JT. SAMHD1 is a single-stranded nucleic acid binding protein with no active site-associated nuclease activity. Nucleic Acids Res. 2015 PubMed PMID: 26101257.
Hansen EC, Seamon KJ, Cravens SL, Stivers JT. GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state. Proc Natl Acad Sci U S A. 2014 PubMed PMID: 24753578.
Weil AF, Ghosh D, Zhou Y, Seiple L, McMahon MA, Spivak AM, Siliciano RF, Stivers JT. Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration. Proc Natl Acad Sci U S A. 2013 PubMed PMID: 23341616.
Nabel CS, Jia H, Ye Y, Shen L, Goldschmidt HL, Stivers JT, Zhang Y, Kohli RM. AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nat Chem Biol. 2012 PubMed PMID: 22772155.
Parker JB, Bianchet MA, Krosky DJ, Friedman JI, Amzel LM, Stivers JT. Enzymatic capture of an extrahelical thymine in the search for uracil in DNA. Nature. 2007 PubMed PMID: 17704764.