# Validation of EP400 downstream effectors and potential therapeutic targets in Merkel cell carcinoma

> **NIH NIH R50** · DANA-FARBER CANCER INST · 2020 · $163,938

## Abstract

PROJECT SUMMARY
The role of Human Oncogenic Viruses in Cancer Research
 Tumor viruses are widely spread in human population and are reported to cause 20% of human cancers.
The DNA Tumor Viruses express viral oncoproteins that can specifically target the central nodes of host
cellular networks. Cellular proteins targeted by tumor viruses are often mutated even in non-viral cancers and
very likely to be driving factors of tumorigenesis. While cancer research is normally perplexed by tens of
thousands of passenger mutations that reside in cancer genomes, compact small DNA tumor viruses have
provided advantages for oncologists to focus on a few viral proteins to dissect gene regulatory networks in
cancer. James DeCaprio identified Retinoblastoma Protein (RB1) as the first tumor suppressor using simian
polyomavirus SV40 together with three other groups. Using this approach with continued success, the
DeCaprio laboratory has continued to discover important cellular proteins by identifying SV40 and more
recently Merkel cell polyomavirus T antigen associated proteins. Using SV40 Large T antigen, the DeCaprio
laboratory identified CUL7, CUL9, GLMN, FBWX8, FAM111A, the mammalian DREAM complex and the
MuvB-FoxM1 complex. These novel binding proteins regulate critical cellular processes, and some are
involved in human diseases.
 More recently, the DeCaprio laboratory has focused on Merkel cell polyomavirus (MCPyV) and its
contribution to the highly aggressive Merkel cell carcinoma (MCC). Although MCPyV can infect more than 90%
of the global population, it typically does not cause any symptoms. However, MCPyV can cause MCC, a
disease several times more lethal than melanoma. Given the oncogenic potential of this widespread virus, it is
important for us to understand the functions of human polyomavirus viral antigens and their contribution to
cancer.
Research Specialist’s Activity/Effort:
 Recently, we gained novel insight into the mechanisms of tumorigenesis in MCC. We discovered that
MCPyV small tumor antigen (ST) recruits L-MYC (MYCL) to the EP400 chromatin complex to drive essential
oncogenic processes. I will continue to contribute to the success of Dr. DeCaprio’s research program in the
following areas: (1) Identify downstream targets of ST-MYCL-EP400 complex that are required in
tumorigenesis; (2) Identify therapeutic targets in MCC and test small molecule inhibitors that may inhibit the
viability of MCPyV positive MCC; (3) Generate a mouse model of MCC with targeted integration of MCPyV
tumor antigens into a mouse safe harbor locus. My roles include both direct scientific contributions as well as
specific training of graduate students and technicians in the DeCaprio laboratory.

## Key facts

- **NIH application ID:** 10017929
- **Project number:** 5R50CA243777-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Jingwei Cheng
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,938
- **Award type:** 5
- **Project period:** 2019-09-13 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017929

## Citation

> US National Institutes of Health, RePORTER application 10017929, Validation of EP400 downstream effectors and potential therapeutic targets in Merkel cell carcinoma (5R50CA243777-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017929. Licensed CC0.

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