Shannon Kenney
University of Wisconsin-Madison, WI·Microbiology & Immunology
Epstein-Barr virus (EBV) infects most people for life, usually harmlessly, but it also causes several human cancers. These include lymphomas of the immune system's B cells and nasopharyngeal carcinoma, a tumor of the tissue behind the nose.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Genetics
- Topics
Epstein-Barr virus
viral latency
cyclin D3
- Grants
- 3 known grants, through Feb 2029
What they work on
- Test whether primary human germinal center B cells infected with the lab's EBNA2-deleted EBV mutant, with or without MYC overexpression, form Burkitt-, Hodgkin- or diffuse large B cell lymphoma-like tumors in immunodeficient NSG mice.
- Identify which EBV genes or viral RNAs are required for tumor formation by the EBNA2-deleted virus in naive versus germinal center B cells, with and without the MYC oncogene.
- Define how MYC silences the viral protein LMP1 in these lymphomas, and test whether small molecules that restore LMP1 expression strengthen the T cell response to tumors in humanized mice.
- Determine whether EBNA2-deleted EBV cooperates with overexpressed MYC, BCL6 or cyclin D3 to induce Burkitt-like or germinal-center diffuse large B cell lymphoma-like tumors in NSG mice.
- Test whether activating JAK/STAT signaling, a growth pathway often mutated in Hodgkin lymphoma, or blocking plasma cell differentiation allows EBNA2-deleted EBV to produce Hodgkin-like tumors in cord blood-humanized mice.
- Screen for previously unrecognized cellular gene mutations that cooperate with restricted EBV latency to cause lymphoma in NSG mice, and define the mechanism of that synergy.
- Define how the EBV protein LMP1 activates YAP and TAZ, the growth-promoting outputs of the Hippo tumor-suppressor pathway, to block differentiation of normal oral keratinocytes (NOKs).
- Identify cellular genes and pathways, including the RIPK4/IRF6 differentiation axis, that drive or inhibit lytic EBV reactivation, the switch to making new virus particles, in oral keratinocytes.
- Test whether FDA-approved drugs that inhibit or activate YAP/TAZ block growth of EBV-positive nasopharyngeal and gastric cancer cells expressing LMP1, or alter lytic viral reactivation.
More about the research
A central puzzle is that the virus can transform B cells in a culture dish only when it expresses all nine of its latency proteins, a state called type III latency. That state is easy for the immune system to spot, so real human tumors usually express far fewer viral proteins (type I or type II latency). Until recently there was no laboratory model for how these stripped-down forms of infection cause cancer. Work in this lab centers on building such models and on understanding how EBV behaves in epithelial cells, the lining cells where it also causes disease.
Why it matters
EBV-linked Burkitt, Hodgkin and diffuse large B cell lymphomas and nasopharyngeal carcinoma are serious cancers, and they are especially common in people with weakened immunity such as AIDS patients and transplant recipients. Models that reproduce the restricted forms of viral latency found in actual patient tumors would give the field a way to test treatments. Forcing tumors to re-express the viral protein LMP1 could make them visible to T cells, and already-approved drugs that act on the Hippo pathway could be repurposed against EBV-positive epithelial cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Project 3 - Latent and Lytic EBV Infection in Epithelial Cells
NIH · Feb 1997 – Feb 2029
Roles of LMP1 and MYC in EBV-induced B-cell tumors
NIH · Sep 2023 – Aug 2028
Stringent Latent Epstein-Barr Virus (EBV) Infection Collaborates with Cellular Gene Alterations to Induce EBV+ Lymphomas
NIH · Jul 2023 – Jun 2028
Closest labs
Ethel Cesarman
Weill Medical College of Cornell University, NY·Microbiology & Immunology
Identify how key germinal center cytokines, the signaling proteins in lymph nodes where B cells mature, act on enzymes that chemically mark DNA and histones to alter the EBV genome and choose which latency program the virus uses.
Paul Lieberman
University of Pennsylvania, PA·Microbiology & Immunology
Test whether EBV reshapes the host low-oxygen response during primary infection to keep infected cells alive, examining how the viral proteins EBNA1 and EBNA2 bind and regulate host hypoxia genes including HIF1A.
Abhijit Patel
Yale University, CT·Medicine & Clinical Research
Map the order in which methylation changes in Epstein-Barr virus DNA and host B-cell gene promoters appear in blood before lymphoma is diagnosed, using banked plasma from a long-term cohort of people with HIV.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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