Dr. Meaghan Hancock

My first experience working in a laboratory came during a fourth-year undergraduate course at McMaster University, where I worked in the lab of Dr. Karen Mossman. This was a transformative experience for me, and I fell in love with both the flexibility and intellectual freedom of working at the bench. I became fascinated with herpesviruses and their clever ability to take over an infected cell and turn it into a virus-making factory. Since I knew I wanted to continue in herpesvirology, I moved to the University of Alberta for my graduate degree and worked in the lab of Dr. Jim Smiley, where I focused on understanding the role of the viral proteins VP16 and ICP0 in regulating viral gene expression during herpes simplex virus (HSV) infection. Working with Dr. Smiley gave me not only a firm grounding in molecular virology but also instilled an ongoing curiosity in how herpesviruses can ultimately have very different lifecycles depending on the cell that is infected.

I took this curiosity and training to Oregon Health & Science University, where I started as a post-doctoral fellow in the lab of Dr. Jay Nelson. Dr. Nelson’s group were amongst the first to characterize the virally encoded microRNAs (miRNAs) from human cytomegalovirus (HCMV). We hypothesized that viral miRNAs would play an essential role in viral latency and set out to identify viral miRNA targets and their roles in hematopoietic progenitor cells (HPCs). I continued as a Staff Scientist and Research Assistant Professor in the lab before starting my own research program as an Assistant Professor in 2020.

My hobbies: Quilting, knitting, embroidery, hiking, reading (literary fiction, sci-fi, fantasy), cooking and baking.

• B.Sc. Molecular Biology and Biotechnology, McMaster University
• Ph.D. Molecular Virology, University of Alberta
• Post-doctoral Fellow, Oregon Health & Science University

The research in our laboratory is centered on understanding how HCMV manipulates the infected cell to suppress or support viral gene expression. We study the role of viral proteins and non-coding RNAs in viral latency in CD34⁺ HPCs as well as their role in modulating HPC proliferation and differentiation. Making unique and innovative recombinant viruses is our expertise! We are one of only a few groups in the world that regularly study HCMV infection in human stem/progenitor cells, allowing us to ask relevant questions in the most clinically relevant cell types. We also utilize the only humanized mouse model of HCMV latency to understand how our findings in vitro are translated into a complex biological system.

Ongoing Research Programs:

The role of viral miRNAs in HCMV latency and reactivation

We use bioinformatic and biochemical approaches to identify targets of HCMV miRNAs and then investigate how these proteins and cellular signaling pathways regulate HCMV latency and/or reactivation in CD34⁺ HPCs. Our work has helped identify key regulators of cell signaling in HPCs and how viral miRNAs work together or in opposition to one another to support different stages of infection. There are many HCMV miRNAs, and we continue to discover novel roles for these small RNAs in HCMV infection, so potential projects are numerous!

HCMV UL78 as a novel nuclear-localized GPCR

We recently identified the HCMV-encoded GPCR UL78 as a viral protein essential for efficient reactivation. Intriguingly, a proportion of UL78 is localized to the nucleus. We believe UL78 may be the first nuclear-localized viral GCPR, which has significant implications for its function in CD34⁺ HPCs. We are picking apart the UL78 C-terminal tail to understand how it trafficks to the nucleus, what proteins help it to get there, and how it regulates latency and/or reactivation based on its cellular localization.

UL22A is a viral chemokine binding protein with an unexplored function

Many years ago, UL22A was identified as a viral chemokine binding protein that interacts with the chemokine RANTES. After that, no one looked past this one function of the protein since in vivo models of HCMV that could test the effects of UL22A on RANTES function are scarce. We became interested in UL22A as advanced sequencing techniques identified the UL22A transcript as one of the most abundantly produced during lytic and latent infection. We generated a UL22A mutant virus and showed that UL22A has an essential role in HPC infection. The only other known aspect of UL22A biology is that it is the only viral chemokine binding protein that has tyrosine residues that can be sulfated. We also assessed the importance of these tyrosine residues to UL22A function and showed that they were both essential for virus reactivation and interactions with RANTES. However, we showed that neutralizing RANTES was not necessary for the virus to efficiently reactivate from latency, indicating that UL22A must have other functions aside from binding RANTES.

We are following up these studies with a more biochemical approach to understanding UL22A function, including affinity purification-mass spectrometry to identify additional UL22A interactors, exploring the tyrosine sulfation modification and how neighbouring residues impact the ability of the protein to be sulfated as well as modelling the interactions between UL22A and RANTES as well as additional interactors. We plan to incorporate informative mutations into the viral genome and then assess their importance to latency and reactivation.

• National Institutes of Health (NIH)

• Turner RL, Diggins NL, Slind L, Mitchell J, Pham AH, Parkins CJ, Perez W, Medica S, Denton M, Andoh TF, Webb GM, Andrade-Vera D, Streblow DN, Caposio P, Hancock MH. The human cytomegalovirus chemokine binding protein UL22A is necessary for efficient reactivation from latency in CD34+ hematopoietic progenitor cells and humanized mice. J Virol. 2026; Jul 27

• Medica S, Diggins NL, Denton M, Turner RL, Pung LJ, Mayo AT, Mitchell J, Slind L, Nguyen LK, Beechwood TA, Sulgey G, Kreklywich CN, Malouli D, Caposio P, Streblow DN, Hancock MH. J Virol. 2025; Nov 25;99(11)

• Diggins NL, Pham AH, Mitchell J, Parkins CJ, Slind L, Turner R, Lee BJ, Yurochko AD, Caposio P, Nelson JA and Hancock MH. Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice. PLoS Pathog. 2024; Dec 11;20(12)

• Medica S, Denton M, Diggins NL, Kramer-Hansen O, Crawford LB, Mayo AT, Perez WD, Daily MA, Parkins CJ, Slind LE, Pung LJ, Weber WC, Jaeger HK, Streblow ZJ, Sulgey G, Kreklywich CN, Alexander T, Rosenkilde MM, Caposio P, Hancock MH and Streblow DN. Third intracellular loop of HCMV US28 is necessary for signaling and viral reactivation. J Virol. 2024; Dec 10

• Medica S, Crawford LB, Denton M, Min CK, Jones TA, Alexander T, Parkins CJ, Diggins NL, Streblow GJ, Mayo AT, Kreklywich CN, Smith P, Jeng S, McWeeney S, Hancock MH, Yurochko A, Cohen MS, Caposio P and Streblow DN. Proximity-dependent mapping of the HCMV US28 interactome identified RhoGEF signaling as a requirement for efficient viral reactivation. PLoS Pathog. 2023; Oct 2;19(10).

• Dirck, A*, Diggins, NL*, Crawford, LB, Perez, WD, Parkins, CJ, Struthers HH, Turner, R, Pham, AH, Mitchell, J, Papen, CR, Malouli D, Hancock, MH and Caposio, P. 2023. HCMV UL8 interactin with b-catenin and DVL2 regulates viral reactivation in CD34⁺ hematopoietic progenitor cells. J. Virol. 2023; Oct 31;97(10)

• Diggins NL, and Hancock MH. Viral miRNA regulation of host gene expression. Semin Cell Dev Biol 2023; Sep 1;146:2-19

• Zarrella K, Longmire P, Zeltzer S, Collins-McMillen D, Hancock M, Buehler J, Reitsma JM, Terhune SS, Nelson JA and Goodrum F. Human Cytomegalovirus UL138 interaction with USP1 activates STAT1 in infection. PLoS Pathog. 2023; Jun 8;19(6)

• Hansen SG*, Hancock MH*, Malouli D, Marshall EE, Hughes CM, Randall KT, Morrow D, Ford JC, Gilbride RM, Selseth AN, Espinosa Trethewy R, Bishop LM, Oswald K, Shoemaker R, Berkemeier B, Bosche WJ, Hull M, Nekorchuk M, Busman-Sahay K, Estes JD, Axthelm MK, Smedley J, Shao D, Edlefsen PT, Lifson JD, Fruh K, Nelson JA and Picker LJ. Myeloid cell tropism enables MHC-E-restricted CD8⁺ T cell priming and vaccine efficacy by the RhCMV/SIV vaccine. Science Immunology 2022; Jun 24;7(72) *co-authors

• Crawford LB, Diggins NL, Caposio P, and Hancock MH. Advances in Model Systems for Human Cytomegalovirus Latency and Reactivation. mBio. 2022; Jan 11;13(1)

• Pham AH, Mitchell J, Botto S, Pryke KM, DeFilippis VR and Hancock MH. Human cytomegalovirus blocks canonical TGFb signaling during lytic infection to limit the induction of type I interferons. PLoS Pathogens. 2021; Aug 19;17(8)

• Lee BJ, Min CK, Hancock M, Streblow DN, Caposio P, Goodrum FD and Yurochko AD. Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells. Front Microbiol. 2021 May 7;12

• Malouli D*, Hansen SG*, Hancock MH, Hughes CM, Ford, JC Gilbride RM,…Fruh K and Picker LJ. Cytomegaloviral Determinants of CD8⁺ T cell Programming and RhCMV/SIV Vaccine Efficacy. Science Immunology 2021;6(57) *co-authors

• Diggins NL, Skalsky RL, and Hancock, MH. Regulation of Latency and Reactivation by Human Cytomegalovirus miRNAs. Pathogens 2021; Feb 13;10(2):200

• Diggins N, Crawford, LB, Hancock, MH, Mitchell, J, and Nelson, JA. 2020. Human cytomegalovirus miR-US25-1 targets the GTPase RhoA to inhibit CD34⁺ Hematopoietic progenitor cell proliferation to maintain the latent viral genome. mBio 2021; Apr 6; 12(2).

• Diggins NL, Crawford LB, Struthers HM, Hook LM, Landais I, Skalsky RL and Hancock MH. Techniques for characterizing cytomegalovirus-encoded miRNAs. Methods Mol Biol 2021;2244:301-342

• Zhang S, Springer LE, Rao HZ, Espinosa Trethewy RG, Bishop LM, Hancock MH, Grey F, Snyder CM. Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion. PLoS Pathog. 2021 Jan 28;17(1).

• Hancock, MH, Crawford LB, Perez W, Struthers HM, Mitchell J and Caposio P. Human cytomegalovirus UL7, miR-US5-1 and miR-UL112-3p inactivation of FOXO3a protects CD34 hematopoietic progenitor cells from apoptosis. mSphere, 2021 Jan 6;6(1).

• Crawford LB, Hancock MH, Struthers HM, Streblow DN, Yurochko A, Caposio P, Goodrum FD and Nelson JA. CD34⁺ Hematopoietic Progenitor Cell Subsets Exhibit Differential Ability to Maintain HCMV Latency and Persistence. J Virol. 2021 Jan 13;95(3)

• Hancock MH, Mitchell J, Goodrum FD and Nelson JA. Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and UL138 Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways. mSphere. 2020 Aug 5;5(4)

• Hancock MH*, Crawford LB*, Pham AH, Mitchell J, Struthers HM, Yurochko AD, Caposio P and Nelson JA. Human Cytomegalovirus miRNAs Regulate TGF-b to Mediate Myelosuppression while Maintaining Viral Latency in CD34⁺ Hematopoietic Progenitor Cells. Cell Host Microbe. 2020 Jan 8;27(1) *co-authors

• Mikell I, Crawford LB, Hancock MH, Mitchell J, Buehler J, Goodrum F and Nelson, JA. HCMV miR-US22 down-regulation of EGR-1 regulates CD34⁺ hematopoietic progenitor cell proliferation and viral reactivation. PLoS Pathog. 2019 Nov 14;15(11)

• Crawford LB, Caposio P, Kreklywich C, Pham AH, Hancock MH, Jones TA, Smith PP, Yurochko AD, Nelson JA and Streblow, DN. Human Cytomegalovirus US28 Ligand Binding Activity is Required for Latency in CD34⁺ Hematopoietic Progenitor Cell and Humanized NSG Mice. mBio. 2019 Aug 20;10(4)

• Diggins NL and Hancock, MH. HCMV miRNA Targets Reveal Important Cellular Pathways for Viral Replication, Latency, and Reactivation. Noncoding RNA. 2018 Oct 22;4(4)

• Hancock MH and Nelson, JA. Modulation of the NFkB Signaling Pathway by Human Cytomegalovirus. Virology: Current Research. 2017 Aug;1(1)

• Hancock MH. and R.L. Skalsky. Roles of non-coding RNAs in herpesvirus infection. Current Topics in Micro. and Immun. 2018;419:243-280

• Hancock MH, Hook LM, Mitchell J, Nelson JA. Human Cytomegalovirus MicroRNAs miR-US5-1 and miR-UL112-3p Block Proinflammatory Cytokine Production in Response to NF-κB-Activating Factors through Direct Downregulation of IKKα and IKKβ. mBio 2017 Mar 7;8(2)

• Burwitz BJ, Malouli D, Bimber BN, Reed JS, Ventura AB, Hancock MH, Uebelhoer LS, Bhusari A, Hammond KB, Espinosa Trethewy RG, Klug A, Legasse AW, Axthelm MK, Nelson JA, Park BS, Streblow DN, Hansen SG, Picker LJ, Früh K, Sacha JB. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques. PLoS Pathog. 2016 Nov 9; 12 (11)

• Hook, LM, Hancock MH, Landais I, Grabski R, Britt W, and Nelson JA. Cytomegalovirus microRNAs. Curr Opin Virol 2014 August; (7): 40-46

• Hook LM, Grey F, Grabski R, Tirabassi R, Doyle T, Hancock MH, Landais I, Jeng S, McWeeney S, Britt W, and Nelson JA. Cytomegalovirus miRNAs Target Secretory Pathway Genes to Facilitate Formation of the Virion Assembly Compartment and Reduce Cytokine Secretion. Cell Host and Microbe 2014 March 12; 15(3): 363-73

• Hook LM, Landais I, Hancock MH, and Nelson JA. Techniques for characterizing cytomegalovirus-encoded miRNAs. Methods Mol Biol 2014: 239-65

• Hancock MH, Landais I, Hook LM, Grey F, Tirabassi, R and Nelson JA. “Cytomegalovirus-encoded miRNAs” in Cytomegaloviruses: From Molecular Pathogenesis to Intervention, edited by Matthias Johannes Reddehase and Neils Lemmermann, Norfolk: Caister Academic Press, 2013

• Hancock MH, Tirabassi RS, and Nelson JA. Rhesus cytomegalovirus encodes seventeen microRNAs that are differentially expressed in vitro and in vivo. Virology 2012 Apr 10; 425(2): 133-42

• Hancock MH, Cliffe AR, Knipe DM, and Smiley JR. Herpes Simplex virus VP16, but not ICP0, is required to reduce histone occupancy and enhance histone acetylation on viral genomes in U2OS osteosarcoma cells. J Virol. 2010 Feb; 84(3): 1366-75

• Hancock MH, Mossman KL, and Smiley JR. Cell fusion-induced activation of interferon-stimulated genes is not required for restriction of a herpes simplex virus VP16/ICP0 mutant in heterokarya formed between permissive and restrictive cells. J Virol. 2009 Sep; 83(17): 8976-9 *A JVi Spotlight article of significant interest selected by the editor

• Chew T, Noyce R, Collins SE, Hancock MH, Mossman KL. Characterization of the interferon regulatory factor 3-mediated antiviral response in a cell line deficient for IFN production. Mol Immunol. 2009. Jan;46(3):393-9

• Hancock MH, Corcoran JA, and Smiley, JR. Herpes simplex virus regulatory proteins VP16 and ICP0 counteract an innate intranuclear barrier to viral gene expression. Virology. 2006 Aug 15;352(1):237-52

Chris Parkins

Research Associate II/Lab Manager

Chris obtained his B.Sc. from McMaster University and his M.Sc. from the University of Alberta where he studied mechanisms of axon degeneration. Proficient in wet lab work and animal handling, Chris has also taken on many of the necessary tasks to keep the lab running including ordering, shipping etc. While most of his research career has focused on flaviviruses, Chris is excited to continue his study of cytomegalovirus pathogenesis, latency and reactivation.

Chris enjoys hiking, rock hounding, brewing, woodworking, leatherworking, and beekeeping.