# Role of DNA sensing pathways in KSHV associated cancers

> **NIH NIH R00** · UNIVERSITY OF FLORIDA · 2021 · $245,107

## Abstract

PROJECT SUMMARY/ABSTRACT
Kaposi's sarcoma associated herpesvirus is the etiological agent for several malignancies in the human population
including Kaposi's sarcoma (KS), Multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL).
Although innate immunity has been shown to be important for comprehensive antiviral responses to clear viral
infection and limit viral tumor growth and proliferation, exactly how the innate immune system senses tumor viruses,
such as KSHV, is not well understood at the molecular level. Investigating the interplay between the innate immune
system, KSHV and KSHV-associated cancers will help us develop better therapies to not only treat KSHV related
malignancies, but also broaden our knowledge to other viral cancers. Previously, we have found that cGAS-STING
pathway is responsible for triggering innate immune responses upon KSHV infection. However, KSHV can still
establish lifelong infection in the presence of cGAS-STING signaling, suggesting KSHV viral regulation of cGAS-
STING pathway to suppress innate immunity. In order to identify potential viral regulators, we have developed a
screening system and successfully identified multiple viral proteins that negatively regulate cGAS-STING signaling.
We have also validated one of our candidates, vIRF1, and explored the mechanism of how vIRF1 blocks cGAS-
STING pathway to facilitate KSHV replication. Our results suggest that modulation of cGAS-STING pathway is
important for viral transmission and the lifelong persistence of gammaherpesviruses in the human population.
Therefore, studies in this K99/R00 proposal will build upon these findings to extend our knowledge of how these
viral proteins regulate cGAS-STING pathway and how to develop potential KSHV cancer therapy by targeting these
viral proteins. Specifically, I will focus on: 1) Validating our screening results and exploring detailed mechanisms
of cGAS-STING signaling regulation by our KSHV viral candidates, 2) Utilizing multiple technologies, including
siRNA, recombinant virus, and CRISPR to explore the role of our viral candidates on KSHV pathogenesis in
vitro, 3) Utilizing CRISPR technology to explore the role of our viral candidates in our PEL based mouse model,
4) Screening for drugs that target cGAS-STING pathway, and testing their efficacy in our PEL based mouse
model. With strong mentorships and a detailed training plan, I aim to build a solid foundation for a successful
independent research career investigating the interaction of cGAS-STING pathway and KSHV cancers and
developing potential KSHV cancer treatments.

## Key facts

- **NIH application ID:** 10247832
- **Project number:** 5R00CA230178-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Zhe Ma
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $245,107
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247832

## Citation

> US National Institutes of Health, RePORTER application 10247832, Role of DNA sensing pathways in KSHV associated cancers (5R00CA230178-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247832. Licensed CC0.

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