Professor
Pharmacology and Molecular Sciences Department, School of Medicine
RESEARCH OVERVIEW
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 elucidating how the dNTPase and DNA/RNA binding activities of the enzyme SAMHD1 lead to HIV-1 restriction in macrophages, anticancer drug resistance, and cellular DNA repair. Our long-range goal is to design novel small molecules that inhibit or activate the various activities of SAMHD1 in cells for antiviral, anticancer, and anti-inflammatory therapeutic uses.
Biophysics and Structural Biology | Cancer Biology | Cell Biology | Cellular Stress and Cell Signaling | Chemical Biology and Proteomics | Immunology and Infectious Diseases | Translational Research
Selected Publications
Orris B, Huynh KW, Ammirati M, Han S, Bolaños B, Carmody J, Petroski MD, Bosbach B, Shields DJ, Stivers JT. Phosphorylation of SAMHD1 Thr592 increases C-terminal domain dynamics, tetramer dissociation and ssDNA binding kinetics. Nucleic Acids Research, 2022.
Christenson ES, Gizzi A, Cui J, Egleston M, Seamon KJ, DePasquale M, Orris B, Park BH, Stivers JT. Inhibition of Human Uracil DNA Glycosylase Sensitizes a Large Fraction of Colorectal Cancer Cells to 5-Fluorodeoxyuridine and Raltitrexed but Not Fluorouracil. Molecular Pharmacology, 2021.
Cui J, Gizzi A, Stivers JT. Deoxyuridine in DNA has an inhibitory and promutagenic effect on RNA transcription by diverse RNA polymerases. Nucleic Acids Research, 2019.
Hansen EC, Ransom M, Hesselberth JR, Hosmane NN, Capoferri AA, Bruner KM, Pollack RA, Zhang H, Drummond MB, Siliciano JM, Siliciano R, Stivers JT. Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells. eLife, 2016.
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. PNAS, 2014.
Learn More
NCBI Bibliography | Faculty Profile | Lab Website | LinkedIn