Research
The Coyne Lab currently studies pathways by which microorganisms cross cellular barriers, primarily the epithelium that lines the gastrointestinal tract on placental trophoblasts. Her lab’s long term goal are to identify pathogen- and host-specific therapeutic targets to prevent or treat microbial infections and ultimately to alleviate the morbidity and mortality caused by these infections.
Biography
Dr. Carolyn Coyne was trained in pharmacology and has graduate and post-graduate training in cell biology and microbiology. Dr. Coyne received a B.S. in Biochemistry from Florida State University and then completed her doctoral work in 2003 at the University of North Carolina at Chapel Hill. Her doctoral thesis investigated the impact of inflammation on intercellular junctions in human airway epithelial cells. Dr. Coyne completed a postdoctoral fellowship in the Department of Microbiology/Division of Pediatric Infectious Diseases at the University of Pennsylvania/Children’s Hospital of Philadelphia. Dr. Coyne joined the faculty of the University of Pittsburgh in 2007 as an Assistant Professor, was promoted to Associate Professor with tenure in 2012, and became a Full Professor in the Department of Pediatrics in 2019. Dr. Coyne is the Director for the Center for Microbial Pathogenesis within the Children’s Hospital of Pittsburgh at UPMC and an Associate Director of the Richard King Mellon Pediatric Research Institute. Dr. Coyne’s research program focuses on the mechanisms by which cellular barriers restrict microbial infections and the strategies that microbes have evolved to penetrate these barriers. She is a recognized leader in the field of virus infections of polarized cells, host innate immune signaling, and host-pathogen interactions at the maternal-fetal interface. Dr. Coyne’s work is multidisciplinary and encompasses cell biology, tissue engineering, immunology, and microbiology to dissect the complex dialogue that occurs between virus and host during the course of infection.
Lab Members
Publications
Refereed articles
Morosky S, Wells A, Lemon K, Evans E, Schamus S, Bakkenist CJ, Coyne CB. The neonatal Fc receptor is a pan-echovirus receptor. Proceedings of the National Academy of Science, 2019 2019 Feb 26;116(9):3758-3763. PMID: 30808762.
Good CA, Wells AI, and Coyne CB. Type III interferon signaling restricts enterovirus 71 infection of goblet cells. Science Advances 2019 Mar 6;5(3). PMID: 30854425.
Caine EA, Sceaffer SM, Arora N, Zaiysev K, Artyomov MN, Coyne CB*, Moley KH*, and Diamond MS*. Interferon lambda protects the female reproductive tract against Zika virus infection. Nature Communications, 2019. (*co-corresponding).
McMillen CM, Arora N, Boyles DA, Albe JR, Kujawa MR, Bonadio JF, Coyne CB, and Hartman AL. Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection. Science Advances, 2018 Dec 5;4(12):eaau9812. PMID: 30525107.
Zimmerman MG, Quicke KM, O’Neal JT, Arora N, Machiah D, Priyamvada L, Kauffman RC, Register E, Adekunle O, Swieboda D, Johnson EL4 Cordes S, Haddad L, Chakraborty R, Coyne CB, Wrammert J, Suthar MS. Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages. Cell Host Microbe. 2018 Nov 14;24(5):731-742.e6. PMID: 30439342.
Delorme-Axford E, Abernathy E, Lennemann NJ, Bernard A, Ariosa A, Backues S, Coyne CB, Kirkegaard K, and Klionsky D. The Exoribonuclease Xrn1 Is a Post-Transcriptional Negative Regulator of Autophagy. Autophagy 2018 Mar 21:1-15. PMID: 29465287
Platt DJ, Smith AM, Arora N, Diamond MS, Coyne CB, and Miner JJ. Zika virus-related neurotropic flaviviruses infect human mid-gestation placental explants and cause fetal demise in mice. 2017 Science Translational Medicine 2018 Jan 31;10(426). PMID: 29386359.
Ander SE, Rudzki EN, Arora N, Sadovsky Y, Coyne CB*, Boyle JP*. Human Placental Syncytiotrophoblasts Restrict Toxoplasma gondii Attachment and Replication and Respond to Infection by Producing Immunomodulatory Chemokines. mBio 2018 Jan 9;9(1). PMID: 29317509. (*co-corresponding).
Yockey LJ, Jurado KA, Arora N, Millet A, Rakib T, Milano KM, Hastings AK, Fikrig E, Kong Y, Horvath TL, Weatherbee S, Kliman HJ, Coyne CB, Iwasaki A. Type I interferons instigate fetal demise after Zika virus infection. Science Immunology 2018 Jan 5;3(19) PMID: 29305462.
Bayer A, Lennemann NJ, Ouyang Y, Sadovsky E, Sheridan MA, Roberts MR, Coyne CB*, Sadovsky Y*. Chromosome 19 microRNAs exert antiviral activity independent from type III interferon signaling. Placenta 2018 Jan;61:33-38 PMID: 29277269. (*co-corresponding).
Jagger BW, Miner JJ, Cao B, Arora N, Smith AM, Kovacs A, Mysorekar IU, Coyne CB, and Diamond MS. Gestational stage and IFN-l signaling influence ZIKV infection in utero. 2017 Cell Host & Microbe Sep 13;22(3):366-376 PMID: 28910635.
Corry J, Arora N, Good C, Sadovsky Y, and Coyne CB. Organotypic models of type III interferon-mediated protection from Zika virus infections at the maternal-fetal interface. 2017 Proceedings of the National Academy of Science Aug 29;114(35):9433-9438 PMID: 28784796.
Bramley JC, Drummond CG, Lennemann NJ, Good CA, Kim KS, and Coyne CB. A ThreeDimensional Cell Culture System To Model RNA Virus Infections at the Blood-Brain Barrier. mSphere. 2017 Jun 21;2(3). pii: e00206-17. PMID: 28656176.
Chang G, Mouillet JF, Mishima T, Chu T, Sadovsky E, Coyne CB, Parks WT, Surti U, and Sadovsky Y. Expression and trafficking of placental microRNAs at the feto-maternal interface. The FASEB Journal, 2017 Mar 13. PMID: 28289056
Dumont TF, Mouillet JF, Bayer A, Gardner CL, Klimstra WK, Wolf DG, Yagel S, Balmir F, Binstock A, Sanfilippo JS, Coyne CB, and Sadovsky Y. The expression level of C19MC miRNAs in early pregnancy and in response to viral infection. Placenta, May;53:23-29. PMID: 28487016
Drummond CG, Bolock, AM, Congrong M, Luke CJ, Good, M, and Coyne, CB. Enteroviruses infect human enteroids and induce antiviral signaling in a cell-lineage specific manner. Proceedings of the National Academy of Science 2017, Feb 14;114(7):1672-1677. PMID: 28137842.
Lennemann, NJ and Coyne, CB. Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B. Autophagy 2017 2017 Feb;13(2):322-332. PMID: 28102736
Rausch K, Hackett BA, Weinbren NL, Reeder SM, Sadovsky Y, Hunter CA, Schultz DV, Coyne CB, and Cherry S. Screening Bioactives Reveals Nanchangmycin as a Broad Spectrum Antiviral Active against Zika Virus. Cell Reports, 2017 Jan 17. PMID: 28099856
Ouyang, Y, Bayer A, Chu T, Tyurin V, Kagan V, Morelli AE, Coyne CB, and Sadovsky, Y*. Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity. Placenta 20162016 Nov;47:86-95. PMID: 27780544
Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques Jr. E, Cherry S, Sadovsky Y, and Coyne CB. Human Placental Trophoblasts Produce Type III Interferons that Confer Protection Against Zika Virus Infection. Cell Host & Microbe 2016 Apr 5. PMID: 27066743.
Cuevas RA, Ghosh A, Wallerath C, Hornung V, Coyne CB, and Sarkar SN. MOV10 provides antiviral activity against RNA viruses by enhancing RIG-I-MAVS-independent IFN induction. J. Immunol. 2016 Mar 25. PMID: 27016603.
McConkey C, Delorme-Axford E, Nickerson CA, Kim KS, Sadovsky Y, Boyle JP, and Coyne CB. A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance. Science Advances. 2016 Mar 4;2(3). PMID: 26973875. *Featured on NIH Research Matters https://www.nih.gov/news-events/nih-research-matters/3-dcell-placenta-model-mimics-development-microbial-resistance.
Morosky S, Lennemann NJ, and Coyne CB. BPIFB6 regulates secretory pathway trafficking and enterovirus replication. J. Virology. 2016 Mar 9. PMID: 26962226. *Selected as Spotlight Feature Article.
McCormick KD, Ghosh A, Ferris R, Coyne CB, and Sarkar SN. Innate immune signaling through differential RIPK1 expression promote tumor progression in head and neck squamous cell carcinoma. Carcinogenesis. 2016 Mar 18. PMID: 26992898.
Hendricks MR, Lashua LP, Fishcer DK, Flitter BA, Elchinger KM, Durkin JE, Sarkar SN, Coyne CB, Empey KM, and Bomberger JM. Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity. Proceedings of the National Academy of Science. 2016 Feb 9;113(6):1642-7.
Drummond CG, Nickerson CA, and Coyne CB. A three-dimensional cell culture model to study enterovirus infection of polarized intestinal epithelial cells. mSphere 2016 Jan 1(1).
Harris KG and Coyne CB, Unc93b induces apoptotic cell death and is cleaved by host and enteroviral proteases. PLoS One, 2015 Oct 28;10(10):e0141383.
Shu Q, Lenneman N, Sarkar SN, Sadovsly Y, and Coyne CB. ADAP2 is an interferon stimulated gene that alters virus entry. PLoS Pathogens, 2015 Sep 15;11 (9), 2015.
Harris KG, Morosky SA, Drummond CG, Patel M, Kim C, Stolz, DB, Bergelson JM, Cherry S, and Coyne CB. RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection of Intestinal Epithelial Cells. Cell Host & Microbe, Volume 18, Issue 2, p221–232, 2015.
Rosenthal AK, Gohr CM, Mitton-Fitzgerald E, Grewal R, Ninolya J, Coyne CB, and Jackson WJ. Autophagy Modulates Articular Cartilage Vesicle Formation in Primary Articular Chondrocytes. 2015 May 22;290(21), J Biol Chem. 2015.
Delorme-Axford E, Morosky S, Bomberger J, Stolz DB, Jackson WT, and Coyne CB. BPIFB3 regulates autophagy and Coxsackievirus B replication through a noncanonical pathway independent of the core initiation machinery. MBio. 2014 Dec 9;5(6):e02147.
Bayer A, Delorme-Axford E, Sleigher C, Frey TK, Trobaugh DW, Klimstra WB, Emert-Sedlak L, Smithgall TS, Kinchington PR, Vadia S, Seveau S, Coyne CB††, and Sadovsky Y††. (††cocorresponding). Human trophoblasts confer resistance to viruses implicated in perinatal infection. Amer. J. Ob. Gyn. 2014, 2014 Aug 6.
Zhu J, Zhang Y, Ghosh A, Cuevas RA, Forero A, Dhar J, Ibsen MS, Schmid-Burgk JL, Schmist T, Ganapathiraju MK, Fujita T, Hartmann R, Barik S, Hornung V, Coyne CB, and Sarker SN. Antiviral activity of human OASL is mediated by enhancing RIG-I signaling. Immunity. 2014 Jun 19;40(6):936-48
Jacobs JL, Zhu J, Sarkar SN, and Coyne CB. Regulation of mitochondrial antiviral signaling (MAVS) expression and signaling by the mitochondria-associated endoplasmic reticulum membrane (MAM) protein Gp78. J. Biol. Chem, 2014, Jan 17;289(3):1604-16.
Delorme-Axford E*, Donker RB*, Mouillet JF, Chu T, Bayer A, Ouyang Y, Wang T, Stolz DB, Sarkar SN, Morelli AE, Sadovsky Y††, and Coyne CB†† (†† co-corresponding). Human placental trophoblasts confer viral resistance to recipient cells. Proceedings of the National Academy of Sciences, 2013, 2013 Jul 16;110(29):12048-53. Cozzarelli Prize for best Biomedical Sciences (Class IV) publication in PNAS in 2013.
Delorme-Axford E, Sadovsky Y, and Coyne CB. Lipid-raft- and Src family kinase-dependent entry of Coxsackievirus B (CVB) into human placental trophoblasts. Journal of Virology. 2013, Aug; 87 (15): 8569-81.
Bozym R, Delorme-Axford E, Harris K, Morosky S, Ikizler M, Dermody TS, Sarkar SN, and Coyne CB. Focal adhesion kinase is a component of RIG-I-like Receptor Signaling. Cell-Host Microbe, Feb 16;11(2):153-66. 2012. PMID: 22341464.
Zhu, J, Coyne CB, and Sarkar SN. PKC alpha regulates Sendai virus mediated Interferon induction through HDAC6 and beta-catenin. EMBO J. 2011 Sep 27;30(23):4838-4. PMID: 21952047.
Bozym RA, Patel K, White C, Cheung KH, Bergelson JM, Morosky SA, Coyne CB. Calcium signals and Calpain-dependent Necrosis are essential for Release of Coxsackievirus B from Polarized Intestinal Epithelial Cells. Mol Biol Cell. 2011 Jul 7. PMID: 21737691
Morosky SA, Zhu J, Mukherjee A, Sarkar SN, Coyne CB. Retinoic-acid induced gene-1 (RIG-I) associates with nucleotide-binding oligomerization domain-2 (NOD2) to negatively regulate inflammatory signaling. J Biol Chem. 2011 Jun 20. PMID: 21690088
Mukherjee A, Morosky, SA, Delorme-Axford, E, Dybdahl-Sissoko N, Oberste MS, Wang T, and Coyne CB. The Coxsackievirus B 3Cpro Protease Cleaves MAVS and TRIF to Attenuate Host Type I Interferon and Apoptotic Signaling. PLoS Pathog. 2011 Mar;7(3):e1001311. PMID:21436888
Coyne CB, Bozym R, Morosky SA, Hanna SL, Mukherjee A, Tudor M, Kim KS, Cherry S. Comparative RNAi screening reveals host factors involved in enterovirus infection of polarized endothelial monolayers. Cell Host Microbe. 2011 Jan 20;9(1):70-82. PMID 21238948.
Bozym RA, Morosky SA, Kim KS, Cherry S, and Coyne CB. Release of Intracellular Calcium Stores Facilitates Coxsackievirus Entry into Polarized Endothelial Cells. PLoS Pathog. 2010 Oct 7;6(10), PMID:20949071 Long KR, Yamamoto Y, Baker AL, Watkins SC, Coyne CB, Conway JF, Aridor M. Sar1
assembly regulates membrane constriction and ER export. J Cell Biol. 2010 Jul 12;190(1):115 28.PMID: 20624903
Moser TS, Jones RG, Thompson CB, Coyne CB, Cherry S. A kinome RNAi screen identified AMPK as promoting poxvirus entry through the control of actin dynamics. PLoS Pathog. 2010 Jun 17;6(6):e1000954.PMID: 2058556
Mukherjee, A., Morosky, S.A., Shen, L., Weber, C.R., Turner, R.R., Kim, K.S., Wang, T., and Coyne CB. Retinoic acid induced gene-1 (RIG-I) associates with the actin cytoskeleton via CARD-dependent interactions J Biol Chem, 2009 Mar 6;284(10):6486-94. PMID: 19122199.
Patel KP, Coyne CB, Bergelson JM. Dynamin- and lipid raft-dependent entry of decayaccelerating factor (DAF)-binding and non-DAF-binding coxsackieviruses into nonpolarized cells. J Virol. 2009 Nov;83(21):11064-77. Epub 2009 Aug 26.PMID: 19710132
Liu S, Yang W, Shen L, Turner JR, Coyne CB, Wang T. Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol. 2009 Feb;83(4):2011-4. Epub 2008 Dec 3.PMID: 19052094
Yang W, Qiu C, Biswas N, Jin J, Watkins SC, Montelaro RC, Coyne CB, Wang T. Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of hepatitis C virus. J Biol Chem. 2008 Mar 28;283(13):8643-53. Epub 2008 Jan 22.PMID: 18211898
Beisswenger C, Coyne CB, Shchepetov M, Weiser JN. Role of p38 MAP kinase and transforming growth factor-beta signaling in transepithelial migration of invasive bacterial pathogens. J Biol Chem. 2007 Sep 28;282 (39):28700-8. Epub 2007 Jul 24.
Coyne CB, Shen, L., Turner, J.L., and Bergelson, J.M. Coxsackievirus Entry From Epithelial Tight Junctions Requires Occludin and the Small GTPases Rab34 and Rab5. Cell-Host Microbe, 2007 Sep 13;2(3):181-192. PMID: 18005733
Coyne CB., Kim, K.S., and Bergelson, J.M. Poliovirus Entry into Human Brain Microvascular Cells Requires Receptor-Induced Activation of SHP-2. EMBO J, 2007 Sep 5;26(17):4016-28. PMID: 17717529
Coyne CB and Bergelson J.M., Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell 2006 Jan 13;124(1):119-31. PMID: 16413486
Coyne CB, Pichla, S., Ohman, T., and Bergelson, JM. The Coxsackie Adenovirus Receptor Interacts with the Multi-PDZ Domain Protein-1 Within the Tight Junction. J Biol Chem. 2004 Nov 12;279(46):48079-84
Johnson, L.G., Vanhook, MK, Coyne CB, Haykal-Coates N, and Gavett SJ. Safety and Efficiency of Modulating Paracellular Permeability to Enhance Airway Epithelial Gene Transfer In Vivo. Hum Gene Ther. 2003 May 20;14(8):729-47
Coyne CB, Ribeiro, CMP., Boucher RC, and Johnson LG. Acute mechanism of Medium Chain Fatty Acid-Induced Enhancement of Airway Epithelial Permeability. J Pharmacol Exp Ther. 2003 May;305(2):440-50
Coyne CB, Vanhook, MK, Gambling, TM, Carson, JL, Boucher, RC, and Johnson, LG. Regulation of Airway Tight Junctions by Proinflammatory Cytokines. Mol Biol Cell. 2002 Sep;13(9):3218-34.
Coyne CB, Kelly MM, Boucher RC, Johnson LG. Enhanced epithelial gene transfer by modulation of tight junctions with sodium caprate. Am J Respir Cell Mol Biol 2000 Nov; 23 (5): 602-9