Department of Microbiology

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Faculty Profile

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Jianxin You, Ph.D.

Associate Professor of Microbiology
Department: Microbiology

Contact information
Department of Microbiology
University of Pennsylvania Perelman School of Medicine
201C Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104-6076
Office: 215-573-6781
Fax: 215-898-9557
Graduate Group Affiliations
Education:
M.S. (Biochemistry and Molecular Biology)
University of Maine, 1996.
Ph.D. (Biochemistry and Molecular Biology)
Johns Hopkins, 2001.
Postdoc (Pathology)
Harvard Medical School, 2006.
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Description of Research Expertise

Research Interests

* Human papillomaviruses, Merkel cell polyomavirus, virus-host interaction during persistent latent infection and tumorigenesis

Key words: DNA tumor viruses, Host targets, Persistent latent infection, Episome maintenance, Oncogenesis, Tumor virology, Gene therapy,

Research Details

High-risk type human papillomaviruses (HPVs) such as HPV-16 and -18 are associated with cervical, anogenital, and head and neck cancers. Research in our laboratory studies the molecular mechanisms of papillomavirus-host interaction that allow high-risk HPVs to establish persistent infection and to induce host malignant progression. Our previous work identified the bromodomain protein Brd4 as a key receptor for bovine papillomavirus to gain a foothold on mitotic chromosomes. This study provided the first insight into the cellular machinery essential for papillomavirus retention in host cells. Our recent study demonstrated that Brd4 also plays an important role in the life cycle of Merkel cell polyomavirus, which is a novel human polyomavirus that has recently been discovered in Merkel cell carcinoma, a rare but highly aggressive skin cancer. Our ongoing studies aim to identify novel cellular targets of human papillomavirus and Merkel cell polyomavirus and to understand how the molecular interplays between these two oncogenic DNA tumor viruses and their host targets contribute to tumorigenesis.

Brd4 is also the target of a genetic translocation t(15;19) that defines a highly lethal carcinoma. It has been linked to several other cancers, including acute myeloid leukemia and breast cancer. Using oncogenic DNA tumor viruses and cancer-associated genetic mutations as molecular probes, we are investigating how dysfunction of this important epigenetic reader could lead to human cancers.

Rotation Projects
# There are several possible projects in the areas of human papillomavirus, Merkel cell polyomavirus, and associated tumorigenesis. Students are encouraged to contact Dr. You to discuss possible rotation projects.

Lab Personnel

Jason Diaz, Ph.D. Student
Christine M. Helfer, Ph.D. Student
Wei Liu, Postdoctoral fellow
Sabrina Tsang, Ph.D. Student
Ranran Wang, Postdoctoral fellow
Ji Ho Anh, Research assistant
Kalina Slavkova, Research assistant

Selected Publications

Wang R, Liu W, Helfer CM, Bradner JE, Hornick JL, Janicki SM, French CA, You J: Activation of SOX2 expression by BRD4-NUT oncogenic fusion drives the cellular transformation in NUT midline carcinoma. Cancer Research In press 2014.

Li J, Li Q, Diaz J, You J: Brd4-mediated nuclear retention of the papillomavirus E2 protein contributes to its stabilization in host cells. Viruses In press, In press 2014.

Tsang SH, Wang X, Li J, Buck CB, You J: Host DNA Damage Response Factors Localize to Merkel Cell Polyomavirus DNA Replication Sites to Support Efficient Viral DNA Replication. J Virol In press, In press 2014.

Li J, Wang X, Diaz J, Tsang SH, Buck CB, You J: Merkel Cell Polyomavirus large T antigen disrupts host genomic integrity and inhibits cellular proliferation. J Virol 87(16): 9173-88, Aug 2013 Notes: Chosen as a JVI Spotlight Feature article.doi: 10.1128/JVI.01216-13.

Wang X, Helfer CM, Pancholi N, Bradner JE, You J: Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA. J Virol 87(7): 3871-84, Apr 2013.

Wang X, Li J, Schowalter RM, Jiao J, Buck CB, You J: Bromodomain protein Brd4 plays a key role in Merkel cell polyomavirus DNA replication. PLoS Pathogens 8(11): e1003021, 2012.

Wang R, Li Q, Helfer CM, Jiao J, You J: The bromodomain protein Brd4 associated with acetylated chromatin is important for maintenance of higher-order chromatin structure. J Biol Chem 287: 10738 - 10752, February 2012.

Yan J, Diaz J, Jiao J, Wang R, You J: Perturbation of BRD4 protein function by BRD4-NUT protein abrogates cellular differentiation in NUT midline carcinoma. J Biol Chem 286(31): 27663-75, Aug 2011.

Yan J, Li Q, Lievens S, Tavernier J, You J: Abrogation of the Brd4-positive transcription elongation factor B complex by papillomavirus E2 protein contributes to viral oncogene repression. J Virol 84(1): 76-87, Jan 2010.

You J, Croyle JL, Nishimura A, Ozato K, Howley PM: Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. Cell 117(3): 349-60, Apr 2004.

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Last updated: 10/09/2014
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