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Jianxin You
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Professor of Microbiology
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Department: Microbiology
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Contact information
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Department of Microbiology
3e University of Pennsylvania Perelman School of Medicine
1d 201C Johnson Pavilion
3a 3610 Hamilton Walk
Philadelphia, PA 19104-6076
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3e University of Pennsylvania Perelman School of Medicine
1d 201C Johnson Pavilion
3a 3610 Hamilton Walk
Philadelphia, PA 19104-6076
2e
Office: 215-573-6781
32 Fax: 215-898-9557
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32 Fax: 215-898-9557
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Graduate Group Affiliations
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Publications
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Education:
21 b Ph.D. c
31 Johns Hopkins University, 2001.
21 d Postdoc. c
2f Harvard Medical School, 2006.
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21 b Ph.D. c
31 Johns Hopkins University, 2001.
21 d Postdoc. c
2f Harvard Medical School, 2006.
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Post-Graduate Training
24 3c Graduate Research Assistant, Johns Hopkins University, 49 Department of Biochemistry & Molecular Biology, 1996-2001.
24 32 Postdoctoral Fellow, Harvard Medical School, 1a Department of Pathology, 32 Peter Howley Laboratory, 2001-2006.
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Permanent link24 3c Graduate Research Assistant, Johns Hopkins University, 49 Department of Biochemistry & Molecular Biology, 1996-2001.
24 32 Postdoctoral Fellow, Harvard Medical School, 1a Department of Pathology, 32 Peter Howley Laboratory, 2001-2006.
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a5 Oncogenic virus-driven tumorigenesis, Human papillomavirus, Merkel cell polyomavirus, Immunotherapy for HPV-positive cervical cancer and head & neck cancer
8
10 Keywords
83 STING activation, Cancer immunotherapy, Anti-viral immunotherapy, DNA tumor viruses, Viral oncogenesis, and Tumor virology
8
18 Research Summary
238 Research in my laboratory investigates how the molecular interplay between oncogenic viruses, including Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV), 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.
8
4e Selective reactivation of STING signaling to target “cold” tumors:
31b 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.
8
33 MCPyV infection and Merkel cell carcinoma:
491 MCPyV is a novel human polyomavirus discovered in MCC, a highly aggressive form of skin cancer. However, many aspects of the MCPyV 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.
8
52 Development of new strategies to prevent and treat HPV-associated cancers:
438 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 treat established cancer 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 and curing persistent HPV infections.
5a We are also actively developing new therapies for treating HPV-associated cancers.
8
1a Rotation Projects:
d2 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.
8
16 Lab personnel:
2d Ranran Wang, Ph.D. Research scientist
23 Taylor Senay, Ph.D. Student
23 James Regan, Ph.D. Student
28 Sneha Shirhattikar, FERBS Fellow
2f Meng Jia, Ph.D. Postdoctoral Researcher
34 Vinny Dong, Undergraduate Research Assistant
32 Xiaomei Li, Biotechnology Graduate student
1f Yue Ma, Research Fellow
37 Mykaela (Myka) Salvacion, Research Specialist A
26 Grace Ho, Research Specialist A
26 29
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Description of Research Expertise
23 Research Interestsa5 Oncogenic virus-driven tumorigenesis, Human papillomavirus, Merkel cell polyomavirus, Immunotherapy for HPV-positive cervical cancer and head & neck cancer
8
10 Keywords
83 STING activation, Cancer immunotherapy, Anti-viral immunotherapy, DNA tumor viruses, Viral oncogenesis, and Tumor virology
8
18 Research Summary
238 Research in my laboratory investigates how the molecular interplay between oncogenic viruses, including Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV), 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.
8
4e Selective reactivation of STING signaling to target “cold” tumors:
31b 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.
8
33 MCPyV infection and Merkel cell carcinoma:
491 MCPyV is a novel human polyomavirus discovered in MCC, a highly aggressive form of skin cancer. However, many aspects of the MCPyV 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.
8
52 Development of new strategies to prevent and treat HPV-associated cancers:
438 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 treat established cancer 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 and curing persistent HPV infections.
5a We are also actively developing new therapies for treating HPV-associated cancers.
8
1a Rotation Projects:
d2 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.
8
16 Lab personnel:
2d Ranran Wang, Ph.D. Research scientist
23 Taylor Senay, Ph.D. Student
23 James Regan, Ph.D. Student
28 Sneha Shirhattikar, FERBS Fellow
2f Meng Jia, Ph.D. Postdoctoral Researcher
34 Vinny Dong, Undergraduate Research Assistant
32 Xiaomei Li, Biotechnology Graduate student
1f Yue Ma, Research Fellow
37 Mykaela (Myka) Salvacion, Research Specialist A
26 Grace Ho, Research Specialist A
26 29
23
100 Yang JF, Liu W, You J.: Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential. PLoS Pathog 19: e1011598, Aug 2023.
113 Liu W, Alameh MG, Yang JF, Xu JR, Lin PJC, Tam YK, Weissman D, You J.: Lipid Nanoparticles Delivering Constitutively Active STING mRNA to Stimulate Antitumor Immunity. Int J Mol Sci 23: 14504, Nov 2022.
136 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.
fe Wang R, Yang JF, Senay TE, Liu W, You J.: Characterization of the Impact of Merkel Cell Polyomavirus-Induced Interferon Signaling on Viral Infection. J Virol 97: e0190722, Apr 2023.
dc Liu W, You J. : Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication. Annual Review of Virology 7(1): 289-307, Sep 2020.
cd Krump Nathan A, You Jianxin: Molecular mechanisms of viral oncogenesis in humans. Nature Reviews Microbiology 16(11): 684-698, 2018
77 Liu W, Yang R, Payne AS, Schowalter RM, Spurgeon ME, Lambert PF, Xu X, Buck f9 CB, You J.: Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus Infection. Cell Host Microbe. 19(6): 775-87, June 2016 Notes: Recommended in F1000Prime as being of special significance in the field.
d0 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 6d in NUT midline carcinoma. Proc. Natl. Acad. Sci. USA 114(27): E5352-E5361, July 2017.
13b 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.
d5 Liu Wei, MacDonald Margo, You Jianxin: Merkel cell polyomavirus infection and Merkel cell carcinoma. Curr. Opin. Virol. 20: 20-27, Aug 2016.
10b 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.
fe 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.
2c
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Selected Publications
11a Wang R, Senay TE, Luo TT, Liu W, Regan JM, Salisbury NJH, Galloway DA, You J.: Merkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection. PLoS Pathog 20: e1012170, Jul 2024.100 Yang JF, Liu W, You J.: Characterization of molecular mechanisms driving Merkel cell polyomavirus oncogene transcription and tumorigenic potential. PLoS Pathog 19: e1011598, Aug 2023.
113 Liu W, Alameh MG, Yang JF, Xu JR, Lin PJC, Tam YK, Weissman D, You J.: Lipid Nanoparticles Delivering Constitutively Active STING mRNA to Stimulate Antitumor Immunity. Int J Mol Sci 23: 14504, Nov 2022.
136 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.
fe Wang R, Yang JF, Senay TE, Liu W, You J.: Characterization of the Impact of Merkel Cell Polyomavirus-Induced Interferon Signaling on Viral Infection. J Virol 97: e0190722, Apr 2023.
dc Liu W, You J. : Molecular Mechanisms of Merkel Cell Polyomavirus Transformation and Replication. Annual Review of Virology 7(1): 289-307, Sep 2020.
cd Krump Nathan A, You Jianxin: Molecular mechanisms of viral oncogenesis in humans. Nature Reviews Microbiology 16(11): 684-698, 2018
77 Liu W, Yang R, Payne AS, Schowalter RM, Spurgeon ME, Lambert PF, Xu X, Buck f9 CB, You J.: Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus Infection. Cell Host Microbe. 19(6): 775-87, June 2016 Notes: Recommended in F1000Prime as being of special significance in the field.
d0 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 6d in NUT midline carcinoma. Proc. Natl. Acad. Sci. USA 114(27): E5352-E5361, July 2017.
13b 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.
d5 Liu Wei, MacDonald Margo, You Jianxin: Merkel cell polyomavirus infection and Merkel cell carcinoma. Curr. Opin. Virol. 20: 20-27, Aug 2016.
10b 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.
fe 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.
2c