Assistant Professor
Epidemiology
3302 Michael Hooker
How did I end up at UNC Chapel Hill?
I am NIH funded virologist working at the host pathogen interface to develop new methods of viral control. After receiving my bachelor’s degree in Microbiology from the University of New Hampshire in 1999, I moved to Boston to try to make a career in music but soon realized I enjoyed pipetting more than playing guitar. In 2003, began graduate school in the Department of Microbiology and Immunology at UNC Chapel Hill in the laboratory of Ralph Baric where I focused on pathogenesis of the recently emerged SARS coronavirus. After a postdoc on hepatitis C virus with 2020 Nobel Laureate Dr. Charles M. Rice at the Rockefeller University, I moved back to North Carolina to be an Investigator developing host targeting small molecules as antivirals at GlaxoSmithKline in 2014. In 2015, I became an Assistant Professor in the Department of Epidemiology in the UNC Gillings School of Global Public Health. In 2021, I gained a secondary appointment in the Department of Microbiology and Immunology in the School of Medicine.
Research
RNA virus pathogenesis and antiviral treatment design
My current research is focused RNA virus pathogenesis and antiviral treatment design with an emphasis on coronavirus and flavivirus. For the past 8 years, we have been working with industry and academic partners to develop new antiviral therapies for emerging coronavirus. In collaboration with Gilead Sciences and Emory Institute of Drug Discovery, we accelerated the preclinical development of several broad-spectrum small molecule antiviral drugs two of which are now FDA approved to treat COVID-19, remdesivir and molnupiravir. As five new coronaviruses have emerged in the past 20 years, it is likely that we see future emergence of novel coronavirus. Thus, the development of broadly acting therapies for current and future emerging coronavirus will remain the focus of my research for some time.
Host genetics and chronic viral infections of the liver
Hepatitis C virus (HCV) causes chronic infection of the liver in most humans infected. If left untreated, it can cause liver disease or liver cancer requiring liver transplant for survival. A relative of HCV, Norway rat hepacivirus (NrHV), was recently discovered to cause chronic liver infection in rats in New York City but self-resolving acute infection in typical laboratory mice. We have developed several chronic hepatitis models with NrHV using the Collaborative Cross, a genetically diverse mouse reference population created in the Department of Genetics at UNC. With these models, we aim to identify the genes and pathways that drive clearance, chronicity, and potentially cancer. These studies will provide unique insights into the molecular mechanisms guiding hepacivirus pathogenesis and how host genetic variation affects the innate and adaptive antiviral response.
Link to all publications: https://www.ncbi.nlm.nih.gov/myncbi/1FYGjfCI09/bibliography/public/
Select References:
Schafer A, Martinez DR, Won JJ, Meganck RM, Moreira FR, Brown AJ, Gully KL, Zweigart MR, Conrad WS, May SR, Dong S, Kalla R, Chun K, Du Pont V, Babusis D, Tang J, Murakami E, Subramanian R, Barrett KT, Bleier BJ, Bannister R, Feng JY, Bilello JP, Cihlar T, Mackman RL, Montgomery SA, Baric RS, Sheahan TP. Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice. Sci Transl Med. 2022:eabm3410.
Schafer A, Muecksch F, Lorenzi JCC, Leist SR, Cipolla M, Bournazos S, Schmidt F, Maison RM, Gazumyan A, Martinez DR, Baric RS, Robbiani DF, Hatziioannou T, Ravetch JV, Bieniasz PD, Bowen RA, Nussenzweig MC, Sheahan TP. Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo. J Exp Med. 2021;218(3)
Mollan KR, Eron JJ, Krajewski TJ, Painter W, Duke ER, Morse CG, Goecker EA, Premkumar L, Wolfe CR, Szewczyk LJ, Alabanza PL, Loftis AJ, Degli-Angeli EJ, Brown AJ, Dragavon JA, Won JJ, Keys J, Hudgens MG, Fang L, Wohl DA, Cohen MS, Baric RS, Coombs RW, Sheahan TP, Fischer WA. Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates. Clin Infect Dis. 2021.
Martinez DR, Schafer A, Leist SR, Li D, Gully K, Yount B, Feng JY, Bunyan E, Porter DP, Cihlar T, Montgomery SA, Haynes BF, Baric RS, Nussenzweig MC, Sheahan TP. Prevention and therapy of SARS-CoV-2 and the B.1.351 variant in mice. Cell Rep. 2021;36(4):109450.
Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, Agostini ML, Leist SR, Schafer A, Dinnon KH, 3rd, Stevens LJ, Chappell JD, Lu X, Hughes TM, George AS, Hill CS, Montgomery SA, Brown AJ, Bluemling GR, Natchus MG, Saindane M, Kolykhalov AA, Painter G, Harcourt J, Tamin A, Thornburg NJ, Swanstrom R, Denison MR, Baric RS. An orally bioavailable broad- spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020;12(541). (Preclinical assessment of molnupiravir)
Sheahan TP, Sims AC, Leist SR, Schafer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE, Bauer L, Sellers S, Porter D, Feng JY, Cihlar T, Jordan R, Denison MR, Baric RS. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222. (One of the 50 most read Nature Communications articles in 2020)
Leist SR, Dinnon KH, 3rd, Schafer A, Tse LV, Okuda K, Hou YJ, West A, Edwards CE, Sanders W, Fritch EJ, Gully KL, Scobey T, Brown AJ, Sheahan TP, Moorman NJ, Boucher RC, Gralinski LE, Montgomery SA, Baric RS. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice. Cell. 2020;183(4):1070-1085 e1012.
Dinnon KH, 3rd, Leist SR, Schafer A, Edwards CE, Martinez DR, Montgomery SA, West A, Yount BL, Jr., Hou YJ, Adams LE, Gully KL, Brown AJ, Huang E, Bryant MD, Choong IC, Glenn JS, Gralinski LE, Sheahan TP, Baric RS. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature. 2020;586(7830):560-566.
Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, Leist SR, Pyrc K, Feng JY, Trantcheva I, Bannister R, Park Y, Babusis D, Clarke MO, Mackman RL, Spahn JE, Palmiotti CA, Siegel D, Ray AS, Cihlar T, Jordan R, Denison MR, Baric RS. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396). (Preclinical assessment of remdesivir)
Leist SR, Jensen KL, Baric RS, Sheahan TP. Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis. PLoS One. 2019;14(7):e0220126.
Brown AJ, Won JJ, Graham RL, Dinnon KH, 3rd, Sims AC, Feng JY, Cihlar T, Denison MR, Baric RS, Sheahan TP. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019;169:104541.
Sheahan T, Imanaka N, Marukian S, Dorner M, Liu P, Ploss A, Rice CM. Interferon lambda alleles predict innate antiviral immune responses and hepatitis C virus permissiveness. Cell Host Microbe. 2014;15(2):190-202. (My big postdoc paper)
Sheahan T, Rockx B, Donaldson E, Sims A, Pickles R, Corti D, Baric R. Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium. J Virol. 2008;82(5):2274-2285. (My first “first author” publication from grad school)
