# Functional Characterization of HER Family Variant Biology and Resistance in Cancer

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $248,999

## Abstract

Project Summary/Abstract
Dr. Tikvah Hayes is a postdoctoral research fellow in the laboratory of Dr. Matthew Meyerson at the Dana-Farber
Cancer Institute and the Broad Institute. Her long-term career goal is to reduce cancer-associated mortality and
suffering by determining the mechanisms of cancer development and identifying attractive therapeutic strategies
for better patient care. To accomplish this goal, Dr. Hayes uniquely leverages both functional genomics and
molecular biology methods to answer fundamental questions related to cancer biology.
The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases (RTK) is frequently altered
in cancer. Targeted panel sequencing of patient tumors has revealed a number of activating alterations in both
EGFR and HER2. As a consequence, several generations of molecularly targeted EGFR and HER2 therapies
have been designed and have proved efficacious for some patients with either EGFR- or HER2-mutant cancers.
However, a subset of patient-observed HER family variants lacking a reported function persist and in the absence
of functional data are classified as variants of unknown significance. It remains unknown whether all EGFR and
HER2 missense mutations are oncogenic drivers and are sensitive to clinical EGFR or HER2-targeted therapies.
This proposal aims to functionally and mechanistically characterize the role of EGFR and HER2 missense
variants in promoting oncogenesis and resistance to tyrosine kinase inhibitor (TKI) therapies. Aim 1 will seek to
nominate alternative strategies for patients harboring rare EGFR mutations where no clinically approved EGFR-
targeted therapy exists. Aim 2 will evaluate the oncogenic capacity of rare EGFR variants. Finally, in Aim 3,
HER2 variant oncogenic capacity and TKI sensitivity will be interrogated. The proposed research will greatly
improve our understanding of how RTK missense variants promote cancer development and resistance to
targeted therapies.
Dr. Hayes will learn new techniques which will include organoid culturing, in vivo cell line xenografts, intrathoracic
lung injections, tumor imaging and tissue processing/staining, while simultaneously enhancing her career
development through training in grant-writing, science communication, and leadership. During the K99 phase,
Dr. Hayes’ research and training will be carried out under the primary mentorship of Dr. Matthew Meyerson, a
leader in cancer genomics, and will be additionally complemented by collaborations with experts in high-
throughput genetic screening, clinical genomics, structural biology, and in vivo mouse modeling, as well as
mentoring from an advisory committee consisting of Drs. Michael Eck, William Hahn, Pasi Janne, and Carla Kim.

## Key facts

- **NIH application ID:** 10746883
- **Project number:** 4R00CA248836-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Tikvah K Hayes
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $248,999
- **Award type:** 4N
- **Project period:** 2021-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746883

## Citation

> US National Institutes of Health, RePORTER application 10746883, Functional Characterization of HER Family Variant Biology and Resistance in Cancer (4R00CA248836-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10746883. Licensed CC0.

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