Positions

Research Areas research areas

Overview

  • Studies of DNA Tumor Viruses have been central to modern cancer research. Tumor viruses cause 10-15% of human cancers world-wide and have provided profound insights into both infectious and non-infectious cancer causes. Viral proteins tend to hijack central nodes of cellular networks, such as tumor suppressors p53 and RB, that are frequently mutated in non-viral cancers and likely to be the driver mutations. Therefore, studies of tumor virus oncoproteins and cancer genome sequencing have been two complementary approaches to increase the specificity of cancer gene identification.

    Polyomaviruses are a family of 5 kb double-stranded circular DNA viruses. During the last decade, more than 10 new human polyomaviruses have been discovered. Several human polyomaviruses cause severe diseases. In particular, Merkel cell polyomavirus (MCV) causes the neuroendocrine skin cancer Merkel cell carcinoma (MCC). Virus negative MCC has also been discovered with many UV signature mutations. These two subtypes of MCC with different etiologies seem to converge on the same pathways and elicit nearly identical pathological phenotypes. To seek mechanism-based treatment for MCC, we recently determined that the MCV ST antigen recruits oncoprotein L-MYC to the Tip60-p400 complex, which functions as a powerful engine to transactivate gene expression and promote oncogenesis. By integrating ChIP-seq, RNA-seq and genome-scale CRISPR/Cas9 screens in MCC cells, we have identified several druggable targets downstream of the L-MYC and Tip60-p400 complex, such as PRMT5. Although neuroendocrine tumors occur in many different parts of the body, they are treated as a group of tissue due to common features. For example, MCC cells look very similar to small cell lung cancer (SCLC) cells and MCC has been treated akin to SCLC. The causal relationship between MCV and MCC provides a great tool to understand the biology of a group of cancers that start in neuroendocrine cells. The oncogenic activities of the Tip60-p400 complex identified in VP-MCC that is driven by L-MYC may also be further validated in cancers driven by oncoproteins c-MYC and N-MYC. MYC proteins are overexpressed in 50% of human cancers, e.g. L-MYC is often overexpressed in SCLC. MYC proteins are notoriously “undruggable” due to the lack of enzymatic activity or any deep pocket. Future cure for MYC-driven cancers rely on studies of MYC interacting epigenetic regulators or downstream effectors.

    The lab is currently interested in identifying transforming proteins and oncogenes targeted by small DNA tumor viruses including polyomaviruses. We are particularly interested in the interplay between two MAX network components in Merkel cell carcinoma oncogenesis: the MCV ST, L-MYC and Tip60-p400 complex (SLaP) mediated transcriptional activation and the Polycomb Repressive Complex 1.6 (PRC1.6) mediated transcriptional repression. We are working on understanding how the m6A RNA methylation and PRMT5-mediated symmetric dimethylarginine (SDMA) formation on splicing factors safeguard proper splicing of proliferation-associated genes in cancers where MYC-driven global excess of pre-mRNA may overwhelm the splicing machinery.
  • Publications

    Academic Article

    Year Title
    2021 The Merkel Cell Polyomavirus T Antigens Function as Tumor Promoters in Murine Skin.Cancers.  13:222-222. 2021
    2020 Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.Nature Cell Biology.  22:603-615. 2020
    2020 ViroPanel: Hybrid Capture and Massively Parallel Sequencing for Simultaneous Detection and Profiling of Oncogenic Virus Infection and Tumor Genome.Journal of Molecular Diagnostics.  22:476-487. 2020
    2020 Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.Genome Medicine.  12:30. 2020
    2019 Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 responseProceedings of the National Academy of Sciences of the United States of America.  116:1027-1032. 2019
    2017 Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell CarcinomamBio.  8. 2017
    2017 Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesisPLoS Pathogens.  13:e1006668-e1006668. 2017
    2016 Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for TransformationPLoS Pathogens.  12:e1006020-e1006020. 2016
    2015 Tumorigenic Activity of Merkel Cell Polyomavirus T Antigens Expressed in the Stratified Epithelium of MiceCancer Research.  75:1068-1079. 2015
    2015 Malawi Polyomavirus Is a Prevalent Human Virus That Interacts with Known Tumor SuppressorsJournal of Virology.  89:857-862. 2015
    2013 Tumor-Specific T Cells in Human Merkel Cell Carcinomas: A Possible Role for Tregs and T-Cell Exhaustion in Reducing T-Cell ResponsesJournal of Investigative Dermatology.  133:1879-1889. 2013
    2013 Merkel Cell Polyomavirus Large T Antigen Has Growth-Promoting and Inhibitory ActivitiesJournal of Virology.  87:6118-6126. 2013
    2012 Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirusJournal of Clinical Investigation.  122:4645-4653. 2012
    2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteinsNature Nature: New biology.  487:491-495. 2012
    2012 Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper FactorPLoS Pathogens.  8:e1002949-e1002949. 2012
    2009 Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigensSeminars in Cancer Biology.  19:218-228. 2009

    Education And Training

  • B.S. Biotechnology, Peking University
  • Ph.D. Biochemistry, University of Illinois at Urbana-Champaign
  • Full Name

  • Jingwei Cheng
  • Mailing Address

  • University of New Hampshire

    Dept. of Molecular, Cellular and Biomedical Sciences

    46 College Road

    Durham, NH  03824

    United States