Paul Lieberman
University of Pennsylvania, PA·Microbiology & Immunology
Cancer cells grow in crowded places where nutrients run short and oxygen levels swing up and down, and coping with that shortage is one of the defining features of tumors. Epstein-Barr virus, or EBV, is a widespread human herpesvirus tied to cancers of both lymphoid tissue and epithelium, the cell layer that lines body surfaces.
- Fields
Microbiology & Immunology
Biochemistry
Genetics
- Topics
Epstein-Barr virus
gammaherpesvirus
viral latency
- Grants
- 1 known grant, through Aug 2028
What they work on
- 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.
- Determine how oxygen-sensitive control of TET2, a DNA-demethylating enzyme, drives the heavy DNA methylation seen in EBV-linked Burkitt lymphoma and epithelial cancers, and whether hypoxia contributes to silencing of tumor suppressor genes.
- Define how low oxygen changes the binding of the lysine hydroxylase PLOD1 to mapped sites on EBNA1, and whether this interaction controls EBNA1 stability and maintenance of the EBV episome during latent infection.
- Establish how proline and lysine hydroxylases, oxygen-dependent protein-modifying enzymes, regulate the stability and function of the viral proteins EBNA1 and EBNA2.
More about the research
After infection the virus settles into latency, a quiet state in which it keeps its genome inside the cell without producing new virus particles. This project asks how oxygen metabolism steers that latent state and the cancer-promoting changes that can follow.
Why it matters
EBV is behind an estimated 200,000 new cancer cases each year. Clarifying how the virus exploits oxygen-dependent metabolism and signaling to alter DNA methylation, sustain latency, and drive transformation could point to enzymes such as TET2 or PLOD1 as handles for intervening in virus-associated cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Shannon Kenney
University of Wisconsin-Madison, WI·Microbiology & Immunology
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.
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.
Dirk P Dittmer
University of North Carolina at Chapel Hill, NC·Microbiology & Immunology
Develop fully immunocompetent transgenic mice carrying the complete Epstein-Barr virus genome to model EBV-driven epithelial cancers such as nasopharyngeal and gastric carcinoma, and test the in vivo roles of EBV transcription, microRNAs and proteins.
The school
University of Pennsylvania: 90 labs on PI Pages, $2.2B a year on research, 750 research doctorates a year.
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