Associate Professor of Medicine
Associate Professor of Cell Biology
Associate Professor of Molecular Genetics and Microbiology
Associate of the Duke Initiative for Science & Society
Member of the Duke Cancer Institute
Box 3053 DUMC
Durham, NC 27710
Phone: (919) 684-1921
Fax: (919) 684-2790
Email: stacy.horner@duke.edu
Research
The overall goal of our research is to define the virus-host interactions that control the outcome of infection to hepatitis C virus and other Flaviviridae, including dengue virus and Zika virus. Our research is focused on defining the molecular mechanisms of how these viruses activate and evade host innate immune defenses, as well as the RNA regulatory controls to viral infection and immunity. In particular, we are interested in the role that intracellular membranes play in organizing innate immune signaling platforms during RNA virus infection. We are also pioneering efforts to define how the post-transcriptional RNA modification N6-methyladeonsine regulates Flaviviridae virus infection and antiviral innate immunity.
Our lab uses interdisciplinary approaches to study RNA virus-host interactions, combining techniques from cell biology, virology, biochemistry, and RNA biology to reveal the viral and host strategies that regulate viral infection, with the ultimate goal of developing new immunomodulatory strategies for virus treatment and prevention. Our lab actively participates in the Centers for Virology, Host-Microbial Interaction, RNA Biology, and Epigenetics at Duke.
Biography
Stacy Horner received her BA in Biochemistry and Chemistry from Gustavus Adolphus College in St. Peter, MN in 2001. As an undergraduate, she had research experiences with Dr. J. Ellis Bell at Gustavus and Dr. Thomas R. Broker at the University of Alabama, Birmingham. She entered graduate school at Yale University in the Microbiology graduate program where she worked with Dr. Daniel DiMaio. Her graduate research focused on human papillomavirus (HPV) regulation of cellular growth control pathways and also on designing strategies to eliminate HPV DNA from cervical cancer cells. She received her Ph.D. in Microbiology from Yale in 2007.
Building on her interest of virus/host interactions, Dr. Horner joined the laboratory of Dr. Michael Gale Jr. at the University of Washington for her postdoctoral training in 2007. Her postdoctoral research focused on understanding innate immune regulation by hepatitis C virus (HCV), a global human pathogen. During this time, she identified the mitochondrial-associated ER membrane (MAM; a subdomain of the ER located adjacent to mitochondria) as a membrane platform that organizes innate immune signaling and also as the intracellular site of immune regulation by HCV. Dr. Horner’s postdoctoral research was supported by the Irvington Institute Fellowship Program of the Cancer Research Institute.
Dr. Horner joined the faculty of the Molecular Genetics & Microbiology and Medicine departments at Duke University Medical Center in 2013. Her laboratory is interested in understanding the cell biology of antiviral innate immunity and how RNA viruses, including hepatitis C virus, evade innate immunity. Overall, her research uses a interdisciplinary approach, combining techniques from cell biology, virology, biochemistry, and systems biology to reveal the viral and host strategies that coordinate and regulate innate immunity, with the ultimate goal of developing new immunomodulatory strategies for virus treatment and prevention.
Lab Members
Publications
Representative Publications:
McFadden MJ*, Sacco MT*, Murphy KA, Park M, Gokhale NS, Somfleth KY, Horner SM. FTO suppresses STAT3 activation and modulates proinflammatory interferon-stimulated gene expression. bioRxiv. 2021:2021.07.23.453596. doi: 10.1101/2021.07.23.453596. *Co-first.
Sacco MT, Horner SM. Flipping the script: viral capitalization of RNA modifications. Briefings in Functional Genomics. 2021;20(2):86-93. doi: 10.1093/bfgp/elaa025. PMID: 33401298. PMCID: PMC8008163.
McFadden MJ, Horner SM. N(6)-Methyladenosine Regulates Host Responses to Viral Infection. Trends Biochem Sci. 2021;46(5):366-77. doi: 10.1016/j.tibs.2020.11.008. PMID: 33309325. PMCID: PMC8052259.
McFadden MJ, McIntyre ABR, Mourelatos H, Abell NS, Gokhale NS, Ipas H, Xhemalçe B, Mason CE, Horner SM. Post-Transcriptional Regulation of Antiviral Gene Expression by N6-Methyladenosine. Cell Rep. 2021;34(9):108798. doi: 10.1016/j.celrep.2021.108798. PMID: 33657363. PMCID: PMC7981787.
da Silveira WA, Fazelinia H, Rosenthal SB, Laiakis EC, Kim MS, Meydan C, Kidane Y, Rathi KS, Smith SM, Stear B, Ying Y, Zhang Y, Foox J, Zanello S, Crucian B, Wang D, Nugent A, Costa HA, Zwart SR, Schrepfer S, Elworth RAL, Sapoval N, Treangen T, MacKay M, Gokhale NS, Horner SM, Singh LN, Wallace DC, Willey JS, Schisler JC, Meller R, McDonald JT, Fisch KM, Hardiman G, Taylor D, Mason CE, Costes SV, Beheshti A. Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact. Cell. 2020;183(5):1185-201 e20. PMID: 33242417.
Price AM, Hayer KE, McIntyre ABR, Gokhale NS, Abebe JS, Della Fera AN, Mason CE, Horner SM, Wilson AC, Depledge DP, Weitzman MD. Direct RNA sequencing reveals m(6)A modifications on adenovirus RNA are necessary for efficient splicing. Nat Commun. 2020;11(1):6016. PMCID: 7691994.
Williams GD, Gokhale NS, Snider DL, Horner SM. 2020. The mRNA cap 2′-O-methyltransferase CMTR1 regulates the expression of certain interferon-stimulated genes. mSphere. 2020; 5(3):e00202-20. PMCID: 7227766.
McIntyre ABR, Gokhale NS, Cerchietti L, Jaffrey SR, Horner SM*, Mason CE*. Limits in the detection of m(6)A changes using MeRIP/m(6)A-seq. Sci Rep. 2020;10(1):6590. PMCID: 7170965. *Co-corresponding.
Kwock JT, Handfield C, Suwanpradid J, Hoang P, McFadden MJ, Labagnara KF, Floyd L, Shannon J, Uppala R, Sarkar MK, Gudjonsson JE, Corcoran DL, Lazear HM, Sempowski G, Horner SM, MacLeod AS. IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection. Sci Adv. 2020;6(14):eaay3245. PMCID: 7112749.
Gokhale NS, McIntyre ABR, Mattocks MD, Lazear HM, Holley CL, Mason CE*, and Horner SM*. Altered m6A modification of cellular transcripts influences Flaviviridae infection. Molecular Cell. 2020;77(3):542-55 e8. PMCID: 7007864. *Co-corresponding. Highlighted in Nature Reviews Molecular Cell Biology,Featured on the cover of Molecular Cell.
Vazquez C, Tan CY, Horner SM. Hepatitis C virus infection is inhibited by a non-canonical antiviral signaling pathway targeted by NS3-NS4A. J Virol. 2019;93(23):e00725-19. PMCID: 6854490.
Beachboard DC, Park M, Vijayan M, Snider DL, Fernando DJ, Williams GD, Stanley S, McFadden MJ, and Horner SM. The small GTPase RAB1B promotes antiviral innate immunity by interacting with TNF receptor–associated factor 3 (TRAF3). J Biol Chem. 2019; 294(39):14231-14240. PMCID: 31375559.
Williams GD, Gokhale NS, Horner SM. Regulation of Viral Infection by the RNA Modification N6-Methyladenosine. Annu Rev Virol. 2019;6(1):235-53. PMID: 31283446.
Roder AE, Horner SM. Measuring Hepatitis C Virus Envelopment by Using a Proteinase K Protection Assay. Methods Mol Biol. 2019;1911:209-17. PMCID: 6357228.
Roder AE, Vazquez C, Horner SM. The acidic domain of the hepatitis C virus NS4A protein is required for viral assembly and envelopment through interactions with the viral E1 glycoprotein. PLoS Pathog. 2019;15(2):e1007163. PMCID: 6382253.
Dethoff EA, Boerneke MA, Gokhale NS, Muhire BM, Martin DP, Sacco MT, McFadden MJ, Weinstein JA, Messer WB*, Horner SM*, Weeks KM*. Pervasive tertiary structure in the dengue virus RNA genome. Proc Natl Acad Sci U S A. 2018;115(45):11513-8. PMCID: 6233125. *Co-corresponding
Imam H, Khan M, Gokhale NS, McIntyre ABR, Kim GW, Jang JY, Kim SJ, Mason CE, Horner SM, Siddiqui A. N6-methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle. Proc Natl Acad Sci U S A. 2018;115(35):8829-34. PMCID: 6126736.
Wang L, Pittman KJ, Barker JR, Salinas RE, Stanaway IB, Williams GD, Carroll RJ, Balmat T, Ingham A, Gopalakrishnan AM, Gibbs KD, Antonia AL, e MN, Heitman J, Lee SC, Jarvik GP, Denny JC, Horner SM, DeLong MR, Valdivia RH, Crosslin DR, Ko DC. An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease. Cell Host Microbe. 2018;24(2):308-23 e6. PMCID: 6093297.
Liu B, Merriman DK, Choi SH, Schumacher MA, Plangger R, Kreutz C, Horner SM, Meyer KD, Al-Hashimi HM. A potentially abundant junctional RNA motif stabilized by m(6)A and Mg(2). Nat Commun. 2018;9(1):2761. PMCID: 6050335.
McFadden MJ, Mitchell-Dick A, Vazquez C, Roder AE, Labagnara KF, McMahon JJ, Silver DL, Horner SM. A Fluorescent Cell-Based System for Imaging Zika Virus Infection in Real-Time. Viruses. 2018;10(2). doi: 10.3390/v10020095. PMCID: 5850402.
For a complete list of publications, click here.