# Rewiring of epigenetic DNA damage response pathways in HPV-induced cancer

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2022 · $219,210

## Abstract

Project summary/abstract
Infection with human papilloma virus (HPV) causes endemic occurrence of cervical, head and
neck and anal cancers. Radiotherapy is the cornerstone treatment for these tumors. However,
clinical outcomes in patients with locally advanced disease remain poor due to high recurrence
rates. Thus, there is a critical need to improve the efficacy of radiation in these tumors. Epigenetic
signaling pathways play a crucial role in DNA damage response providing suitable clinical targets
for improving the efficacy of radiotherapy. We demonstrate that expression of the HPV proteins
E6 and E7 alters epigenetic signaling in cancer cells. We hypothesize that these epigenomic
alterations cause tumor dependence on alternative epigenetic pathways to cope with DNA
damage. Using a CRISPR/Cas9 screen we discovered that HPV-positive cancer cells selectively
depend on the chromatin modifier NSL1 and the E3 ubiquitin ligase RNF168 to survive radiation.
The goal of this proposal is to determine the mechanisms of DNA damage response (DDR)
regulated by these pathways in the setting of HPV-induced epigenetic changes. Our work will
establish a novel concept of tumor-targeted therapy by harnessing HPV-induced epigenomic
alterations to allow specific targeting of cancer cells while sparing healthy tissues. The work
proposed here will be conducted under the mentorship of Dr. Dennis Hallahan, a leader clinical
and experimental radiation oncology. The candidate is an MD/PhD with training in clinical
radiation oncology who seeks further training in basic research. His long-term goal is to establish
an independent research laboratory studying the role of epigenetics in DDR. It is anticipated that
the project will result in impactful contributions to the fields of DDR and Radiation Oncology and
prepare the candidate for a career as an independent investigator.

## Key facts

- **NIH application ID:** 10576611
- **Project number:** 7K08CA256170-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Michael Goldstein
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $219,210
- **Award type:** 7
- **Project period:** 2022-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10576611

## Citation

> US National Institutes of Health, RePORTER application 10576611, Rewiring of epigenetic DNA damage response pathways in HPV-induced cancer (7K08CA256170-02). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10576611. Licensed CC0.

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