# Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $911,539

## Abstract

Project Summary/Abstract
There is an emerging epidemic of head and neck cancer caused by human papillomavirus (HPV) among both
smokers and nonsmokers. While vaccination of boys and girls prior to genital HPV exposure is likely to reduce
HPV+ HNC, the impact of vaccination won’t be realized for decades. In the meantime, HPV+ HNC patients are
treated with disfiguring surgeries and combined chemoradiation approaches, which are associated with
significant short- and long-term morbidities. Individuals with recurrent/metastatic HPV+ HNC generally
succumb to their disease. My research program will apply new approaches in functional genomics and
mapping networks of physical interactions among cancer proteins in relevant and unique HPV+ HNC
preclinical models to translate cancer dependencies in this malignancy into more effective and less toxic
therapies. In this proposal, I build upon our past success in 1) defining key genomic “driver” alterations in HNC;
2) developing novel therapeutic approaches; and 3) translating our discoveries using relevant preclinical
models into clinical treatments for HNC patients. My future research program seeks to 1) define the key
genetic alterations that mediate HPV+ HNC growth in conjunction with determination of the protein interactome
to identify new therapeutic targets; 2) determine the mechanisms of each target and its role in HPV+ HNC; and
3) translate these findings into new treatments for HPV+ HNC. I will begin with the study of targets that have
emerged in our research as relevant in HPV+ HNC such as alterations that activate phosphatidylinositol 3-
kinase (PI3K) signaling including mutation or amplification of PIK3CA, or PTEN loss, and activation of the
EGFR family member HER3. When relevant, I will extend these findings to other HPV+ cancers including
cervical and anal cancers as well as HPV- HNC, which remain lethal. With deep expertise in the molecular
pathogenesis and care of patients with HNC; experience leading multi-disciplinary teams focused on
translational research approaches for this disease and a rich network of basic science and clinical
collaborators, I am uniquely positioned to succeed in the 7 year research plan delineated in this proposal.

## Key facts

- **NIH application ID:** 10875272
- **Project number:** 5R35CA231998-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jennifer Rubin Grandis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $911,539
- **Award type:** 5
- **Project period:** 2018-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875272

## Citation

> US National Institutes of Health, RePORTER application 10875272, Integrating genomics and the protein interactome for HPV+ head and neck cancer therapy (5R35CA231998-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10875272. Licensed CC0.

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