Christine O'Connor Lab | Lerner Research Institute

Principal Investigator

Christine O‘Connor, PhD

Associate Staff
Email: [email protected]
Location: Cleveland Clinic Main Campus

Research

Human cytomegalovirus (HCMV) is a herpesvirus that is prevalent in the population, where it remains latent, or quiet, in the host for life. However, when an individual’s immune system is weakened or dysregulated, the virus can reawaken, or reactivate, to cause severe complications and often death. Dr. O’Connor’s research focuses on the processes that balance the silenced and active phases of the virus, as well as how reactivation leads to viral pathogenesis and disease progression.

Biography

Dr. O’Connor leads a translational virology research laboratory in Infection Biology at the Lerner Research Institute (LRI) at Cleveland Clinic, focusing on the host-pathogen relationship of herpesviruses and their hosts. Dr. O’Connor obtained her B.S. in Biochemistry/Cell Biology from Bucknell University in Lewisburg, PA in 2000. Following graduation, Dr. O’Connor completed her PhD in Microbiology in 2006 at the University of Virginia in the lab of Dean Kedes, MD/PhD, where she focused on the structure and proteomic composition of gammaherpesvirus capsids. She then completed two postdoctoral fellowships with Tom Shenk, PhD (Princeton) and Eain Murphy, PhD (Cleveland Clinic; current: Upstate Medical University – SUNY) focusing on the role of viral encoded GPCRs and cytomegalovirus infection, as well as mechanisms underlying cytomegalovirus latency and reactivation. In 2014, Dr. O’Connor was appointed an Assistant Professor of Microbiology & Immunology at University at Buffalo – SUNY, and in 2016, she was recruited to Cleveland Clinic, where she was promoted to Associate Staff (Associate Professor equivalent). Dr. O’Connor is also Associate Professor of Molecular Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, a Member of the Graduate Faculty in the School of Biomedical Sciences, Cellular & Molecular Biology Program at Kent State University (Kent, OH), a Member of the Graduate Faculty in the Molecular Virology PhD Program and the Medical Scientist Training Program both of Case Western Reserve University, and a Member of the Molecular Oncology Program in the Case Comprehensive Cancer Center. Dr. O’Connor’s work has resulted in numerous co-authored publications in the virology field, and work in her lab is currently supported by multiple funding sources, including foundation and NIH support. Dr. O’Connor contributes as a peer reviewer for numerous journals and serves as an Academic Associate Editor for the Journal of Medical Virology and an Academic Editorial Board Member for the Journal of Virology, Plos One, and Translational Oncology.

Education & Professional Highlights

"CIMER Trained Mentor" indicates the principal investigator has completed mentorship training based on curriculum from the Center for the Improvement of Mentored Experiences in Research, aimed at advancing mentoring relationships and promoting cultural change in research.

Appointed 2016 Education and Fellowships Fellowship – Cleveland Clinic Molecular Genetics Cleveland, OH USA 2014 Fellowship – Princeton University Molecular Biology Princeton, NJ USA 2010 Graduate School – University of Virginia PhD, Microbiology Charlottesville, VA USA 2006 Undergraduate – Bucknell University BS, Biochemistry/Cell Biology Lewisburg, PA USA 2000 Awards Rising Star Program Recipient (1 of 11 globally) Global Virus Network 2023 Top 25 Peer Reviewer Journal of Virology 2021 Johnson & Johnson WiSTEM2D Scholars Award Program – Finalist for the award in the Sciences (1 of 6 globally) 2017

Research

The betaherpesvirus, human cytomegalovirus (HCMV), is a ubiquitous pathogen that infects 60-80% of the population by 40 years of age. Like all herpesviruses, HCMV infections are life-long, during which the virus remains latent within cells of the host’s hematopoietic compartment. Healthy individuals, for the most part, remain asymptomatic. However, infection is problematic for those with dysregulated immune systems, where reactivation of HCMV from latency can cause severe morbidity and mortality. Research in the O’Connor lab aims to elucidate the host-pathogen relationship during both lytic and latent infection to better understand the factors that influence viral pathogenesis and subsequent disease. The lab currently focuses on three main areas of research: Defining the cellular and viral factors that regulate the balance between latency and reactivation. A complete understanding of the viral and host factors that dictate the balance between latency and reactivation remains elusive. Work from a number of labs including ours reveal chromatin remodeling and cellular signaling aid in regulating the finely tuned balance between these phases of infection. Our current work in this area aims to define the contributions of the viral-encoded GPCRs to establishing and maintaining latency, with a particular focus on how these signaling proteins alter the host cell during viral latency and reactivation. This work is aimed at assessing how the viral GPCRs alter the host cell milieu through rewiring cell signaling networks. Additionally, our findings show the viral genome undergoes three-dimensional organization during latency, though the mechanisms regulating this architectural change are unknown. Further, how transcription factors may function in regulating chromatin architecture during latency and reactivation remains incomplete. Work in these areas are on-going, with the ultimate goal of better understanding the host-pathogen relationship during these phases of infection. Understanding the innate response to human herpesviruses. The initial host response to invading pathogens relies on the innate immune response. HCMV alters innate signaling during lytic and latent infection, and our recent work reveals HCMV targets the DDX41-BTK-STING signaling axis to counter the host innate response. Our current work involves understanding the exact mechanisms by which HCMV regulates the innate restriction factors, as well as further defining roles for DDX41 during HCMV infection. Elucidating the contribution of HCMV in disease progression. HCMV has emerged as a significant pathogen that is more than a bystander in healthy individuals. Indeed, HCMV infection is associated with increased pathogenesis of glioblastoma, and HCMV reactivation is common in patients with ulcerative colitis. The mechanisms by which HCMV contributes to either disease, however, remain elusive. Current work in the lab is aimed at defining mechanisms by which the HCMV-encoded GPCRs alter cellular processes that accelerate glioblastoma progression. Additionally, using established patient-derived colonic epithelial cells in vitro, as well as in silico approaches, we are interrogating the biological mechanisms by which HCMV drives colitis progression and recurrence.

Our Team

Publications

Selected Publications

View publications for Christine O‘Connor, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

1. Baruah V, Krishna BA, Kelly MC, Qi X, O’Connor CM. (2025) Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34+ Kasumi-3 cells. Antiviral Research, 238:106169. PMID: 40250631, PMCID in process

2. Baruah V and O’Connor CM (2024) Cytomegalovirus restricts the innate immune response by nuclear export of host restriction factor DDX41. bioRxiv doi: https://doi.org/10.1101/2024.10.03.616496

3. Akter D, Biswas J, Miller M, Thiele D, Murphy EA, O’Connor CM, Moffat J, Chan GC. (2025) Targeting the host transcription factor HSF1 prevents human cytomegalovirus replication in vitro and in vivo. Antiviral Research, 237:106150. PMID: 40147538, PMCID in process.

4. Dooley AL‡, Freeman MR‡, Beucler MJ, Sanders W, Moorman NJ, Miller WE§, O’Connor CM§ (2024) The human cytomegalovirus vGPCR UL33 is essential for efficient lytic replication in epithelial cells. bioRxiv, PMC11429895

5. Groves IJ and O’Connor CM. (2024) Loopy virus or controlled contortionist? 3D regulation of HCMV gene expression by CTCF-driven chromatin interactions. Journal of Virology, 90(10):e0114824. PMID: 39212383, PMC11495066

6. Mahmud J, Geiler BW, Biswas J, Miller MJ, Myers JE, Matthews SM, Wass AB, O’Connor CM, Chan GC. (2024) Delivery of US28 by incoming HCMV particles rapidly attenuates Akt activity to suppress HCMV lytic replication in monocytes. Science Signaling 17(851): eadn8727. PMID: 39190708, PMC11460310

7. Groves IJ, Matthews SM, O’Connor CM. (2024) Host-encoded CTCF regulates human cytomegalovirus latency via chromatin looping. PNAS 121(10): e2315860121. PMID: 38408244, PMCID: PMC10927566

8. Matthews SM, Groves IJ, O’Connor CM. (2023) Chromatin control of cytomegalovirus infection. mBio, e0032623. PMID: 37439556, PMCID: PMC10470543

9. Wass AB§, Krishna BA§, Herring LE, Gilbert TSK, Nukui M, Groves IJ, Dooley AL, Kulp KH, Matthews, SM, Rotroff DM, Graves LM, O’Connor CM. (2022) Cytomegalovirus US28 regulates cellular EphA2 to maintain viral latency. Science Advances 8(43): eadd1168. PMID: 36288299, PMCID: PMC9604534 (§co-first authors)

10. Krishna BA, Wass AB, Murphy EA, O’Connor CM. (2022) Design of a US28 ORF deletion virus in a temperature-sensitive cytomegalovirus strain fails to promote lytic replication in hematopoietic cells. Viruses 14(6). PMID: 35746751, PMCID: PMC9229150

11. Smith NA, Chan GC§, O’Connor CM§. (2021) Modulation of host cell signaling during cytomegalovirus latency and reactivation. Virology Journal 18(1): 207 PMID: 34663377, PMCID: PMC8524946 (§co-corresponding authors)

12. O’Connor CM§ and Sen GC§. (2021) Innate immune responses to herpesvirus infection. Cells 10(8): 2122 PMID: 34440891, PMCID: PMC8394705 (§co-corresponding authors)

13. Krishna BA, Wass AB, Dooley AL, O’Connor CM. (2021) CMV-encoded GPCR pUL33 activates CREB and facilitates its recruitment to the MIE locus for efficient viral reactivation. Journal of Cell Science, 134: jcs.254268. PMID: 33199520, PMICD: PMC7860128

14. Dooley AL and O’Connor CM. (2020) Regulation of the MIE locus during HCMV latency and reactivation. Pathogens 9(11): 869. PMID: 33113934, PMCID: PMC7690695

15. 1. Krishna BA, Wass AB, O’Connor CM. (2020) Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency. PNAS 117(34): 20860-20867. PMID: 32788362, PMCID: PMC7456108

16. Tu CC, O’Connor CM, Spencer JV. (2020) Identification of a novel signaling complex containing host chemokine receptor CXCR4, IL-10 receptor, and human cytomegalovirus US27. Virology 548:49-58. PMID: 32838946, PMCID: PMC9581496.

17. Krishna BA, Wass AB, O’Connor CM. (2020) The requirement for US28 in establishing and maintaining latency is independent of US27 and US29 gene expression. Frontiers in Cellular and Infection Microbiology 10:186. PMID: 32411622, PMCID: PMC7198828

18. Elder EG, Krishna BA, Williamson J, Lim EY, Poole E, Sedikides GX, Wills M, O’Connor CM, Lehner PJ, Sinclair J. (2019) Interferon-responsive genes are targeted during the establishment of human cytomegalovirus latency. mBio 10(6): e02574-19. PMID: 31796538, PMCID: PMC6890990.

19. Krishna BA, Humby MS, Miller WE, and O’Connor CM. (2019) The human cytomegalovirus G-protein coupled receptor US28 promotes latency by attenuating c-fos. PNAS 116(5): 1755-1764. PMID: 30647114, PMCID: PMC6358704

20. Krishna BA, Humby MS, Miller WE, and O’Connor CM. (2019) The human cytomegalovirus G-protein coupled receptor US28 promotes latency by attenuating c-fos. PNAS 116(5): 1755-1764. PMCID: PMC6358704

21. Nukui M, Murphy EA*, O’Connor CM*. (2018) The natural flavonoid compound deguelin inhibits HCMV lytic replication within fibroblasts.Viruses 10(11): pii: E614. PMCID: PMC6265796 (*co-corresponding authors)

22. Boeck JM, Stowell GA, O’Connor CM, Spencer JV. (2018) The human cytomegalovirus US27 gene product constitutively activates ARE-mediated transcription through Gβγ, PI3K, and NRF-1. J Virol. 92(23):pii: e00644-18. PCMID: PMC6232467

23. Roche KL, Nukui M, Krishna BA, O’Connor CM, Murphy EA. (2018) Selective 4-thiouracil labeling of RNA transcripts within latently infected cells after infection with human cytomegalovirus expressing functional uracil phosphoribosyltransferase. J Virol. 92(21): pii:e00880-18. PMCID: PMC6189490

24. Krishna BA, Miller WE, and O’Connor CM. (2018) US28: HCMV’s Swiss Army Knife. Viruses 10(8): pii: E445. PMCID: PMC6116241 Invited Review.

25. Tu CC, Arnolds KL, O’Connor CM, Spencer JV. (2018) Human cytomegalovirus UL111A and US27 gene products enhance the CXCL12/CXCR4 signaling axis via distinct mechanisms. J. Virol. 92(5):e01981-17. PMCID: PMC5809719

26. O’Connor CM, Nukui M, Gurova K, Murphy EA. Inhibition of the Facilitates Chromatin Transcription (FACT) complex reduces transcription from the HCMV MIEP in models of lytic and latent replication. J Virol. 2016;90(8):4249-53.

27. Humby MS and O’Connor CM. HCMV US28 is important for latent infection of hematopoietic progenitor cells. J Virol. 2015; 90(6): 2959-70.

Careers

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Research News

Common herpesvirus hijacks cellular proteins to establish a lifelong presence

The findings identify potential drug targets for a virus that has no vaccine or cure.

NIH Awards $4.6M to Study Human Cytomegalovirus Latency and Reactivation

Dr. O’Connor’s team will investigate the underlying mechanisms by which human cytomegalovirus manipulates host cells to regulate viral latency and reactivation.