Faculty

Jianxin You, Ph.D.

faculty photo
Associate Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

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
Education:
B.S. (Microbiology)
Fudan University, 1.
M.S. (Cell Biology, Dr. Robert Gundersen)
University of Maine, 1996.
Ph.D. (Biochemistry, Dr. Cecile M. Pickart)
Johns Hopkins, 2001.
Postdoc (Viral Oncology, Dr. Peter M. Howley)
Harvard Medical School, 2006.
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Description of Research Expertise

Research Interests
STING activation, cancer immunotherapy, and oncogenic virus-driven tumorigenesis
Key words: STING activation, cancer immunotherapy, anti-viral immunotherapy, DNA tumor viruses, Viral oncogenesis, and Tumor virology
Research Summary
Research in my laboratory investigates how the molecular interplay between oncogenic viruses and their host cells leads to cancer (Cell 117:349-360, Cell Host Microbe 19:775-87). We also study the function of STING (Stimulator of Interferon Genes) in eliciting antiviral and antitumor innate immunity (Proc Natl Acad Sci U S A. 2020;117:13730-13739). Our overall research goal is to develop innovative therapeutic strategies to block pathogenic viral infection and tumor development.

Selective reactivation of STING signaling to target “cold” tumors:
Tumor immune suppression represents a major obstacle to achieving effective cancer immunotherapy. We recently discovered that STING silencing causes the immunologically “cold” tumor microenvironment of Merkel cell carcinoma (MCC), by blocking cytokine production, and consequently impeding cytotoxic T cell infiltration, activation and killing of tumor cells (Proc Natl Acad Sci U S A. 2020 117:13730-13739). Reactivating STING in MCC cells stimulates antitumor inflammatory cytokine/chemokine production. More importantly, stimulation of STING causes robust cell death in MCCs as well as several other STING-silenced cancers. We are currently developing new strategies to bolster antitumor adaptive immunity in STING-silenced cancers that are often refractory to current therapies.

MCPyV infection and Merkel cell carcinoma:
MCPyV is a novel human polyomavirus discovered in MCC, a highly aggressive form of skin cancer. MCPyV is an abundant virus frequently shed from healthy human skin. However, many aspects of the MCPyV viral life cycle remain poorly understood and it is not clear how MCPyV infection causes MCC. We were the first group to report the mechanistic details of MCPyV replication machinery (PLoS Pathogens 2012;8:e1003021). Our additional studies revealed the host factors required for MCPyV replication as well as the impact of the host DNA damage response (DDR) on MCPyV replication and cellular transformation. In our recent study, we discovered the human skin cell type that is productively infected by MCPyV (Cell Host Microbe 19:775-87). Our study established the first cell culture model for MCPyV infection. Our results illustrated how the major MCC risk factors, such as UV radiation, wounding, and aging, may boost viral infection to induce tumorigenesis. Building on these discoveries, our ongoing studies investigate how the interplay between MCPyV and the host immune defense system may contribute to MCC oncogenesis. The ultimate goal of our study is to develop novel cancer therapeutics for treating MCPyV-induced human cancers.

Development of new antiviral strategies to abrogate HPV-host interaction during latent infection:
High-risk HPV infection is the primary risk factor for cervical, anogenital, and head and neck cancers. Currently available HPV vaccines protect against up to ten major types of cancer-causing HPV strains. However, the vaccines do not protect against the other over 140 HPV types and are not useful for those people who are already infected. Alternative approaches are therefore needed for curing ongoing HPV infections. This is particularly important because high-risk HPVs need to persistently infect host cells for years or even decades in order to accumulate substantial cytogenetic changes for developing invasive tumors. HPVs establish persistent infection by maintaining their genomes as episomes in infected cells. Our previous work identified BRD4 as an important host receptor, which tethers the viral E2 protein/episome complex to mitotic chromosomes to ensure faithful partitioning of viral episomes to daughter cells during mitosis (Cell 117:349-360). Our research aims to develop new antiviral drugs for inhibiting the HPV-host interaction mediated by E2 and BRD4. The goal of this study is to develop effective strategies for curing persisting HPV infections that are not protected by the HPV vaccines.

Rotation Projects:
Depending on the interests of the student, there are several possible projects in the areas described above. Prospective students are encouraged to contact Dr. You to discuss possible rotation projects.

Lab personnel:
Ranran Wang, Ph.D., Research scientist
Wei Liu, Ph.D., Research scientist
Nathan A. Krump, CAMB MVP Ph.D. Student
June F. Yang, CAMB MVP Ph.D. Student
Flora Ho, Undergraduate Researcher
Meghan Perez, Undergraduate Researcher
Emily Sheng, Undergraduate Researcher

Selected Publications

Liu W, Kim GB, Krump NA, Zhou Y, Riley JL, You J.: Selective reactivation of STING signaling to target Merkel cell carcinoma. Proc Natl Acad Sci U S A. 117(24): 13730-13739, June 2020 Notes: doi: 10.1073/pnas.1919690117. Epub 2020 Jun 1.

Liu W, You J. : Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication. Annual Review of Virology 7(1): 289-307, Sep 2020.

Krump Nathan A, You Jianxin: Molecular mechanisms of viral oncogenesis in humans. Nature Reviews Microbiology 16(11): 684-698, 2018

Wang R, Cao XJ, Kulej K, Liu W, Ma T, MacDonald M, Chiang CM, Garcia BA, You J.: Uncovering BRD4 hyperphosphorylation associated with cellular transformation in NUT midline carcinoma. Proc. Natl. Acad. Sci. USA Jun 2017 Notes: pii: 201703071. doi: 10.1073/pnas.1703071114. [Epub ahead of print]

Liu W, Yang R, Payne AS, Schowalter RM, Spurgeon ME, Lambert PF, Xu X, Buck CB, You J.: Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus Infection. Cell Host Microbe. May 2016 Notes: pii: S1931-3128(16)30160-3. doi: 10.1016/j.chom.2016.04.024.[Epub ahead of print]

Liu Wei, Krump Nathan A, MacDonald Margo, You Jianxin: Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts. J. Virol. 92(4), Feb 2018.

Liu Wei, MacDonald Margo, You Jianxin: Merkel cell polyomavirus infection and Merkel cell carcinoma. Curr. Opin. Virol. 20: 20-27, Aug 2016.

Tsang SH, Wang R, Nakamaru-Ogiso E, Knight SA, Buck CB, You J.: The Oncogenic Small Tumor Antigen of Merkel Cell Polyomavirus Is an Iron-Sulfur Cluster Protein That Enhances Viral DNA Replication. J. Virol. 90(3): 1544-1556, Feb 2016 Notes: Chosen as a JVI Spotlight Feature article.

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 74(12): 3332-43, Jun 2014.

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, Nov 2012.

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: 05/08/2021
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