# Identification of genetic collaborators in cancer with a brca2-mutant zebrafish model

> **NIH NIH K01** · OHIO STATE UNIVERSITY · 2021 · $96,808

## Abstract

Project Summary/Abstract
The genetic complexity of cancers impedes identification of key genetic collaborators in carcinogenesis.
Heritable mutations in known cancer-associated genes, such as BRCA2, are strongly linked to cancer risk.
However, somatically acquired mutations contribute significantly to cancer progression. These additional
mutations are often generated through amplification and deletion events (copy number alterations; CNA). CNA
can span large genomic regions and disrupt numerous genes, which impedes identification of cancer drivers. By
defining recurrent cancer-associated CNA in an animal model such as the zebrafish, and comparing these data
to known CNA in human cancers, we can use differences in genomic architecture between species to identify
recurrently disrupted genes in cancers from both species. This approach thus identifies novel, conserved,
candidate driver genes that can be easily assessed in the zebrafish model for their potential to impact
carcinogenesis. The goal for this proposal is to identify and functionally characterize conserved genes that are
recurrently disrupted by CNA in BRCA2-associated human and zebrafish cancers. We have previously shown
genetic similarities between human and zebrafish BRCA2-associated cancers, which include the collaborative
role for tp53 in brca2-associated carcinogenesis and the loss of the wild type alleles for brca2 and/or tp53 in
cancers. Our central hypothesis is that novel, conserved, candidate driver genes that collaborate in BRCA2-
associated carcinogenesis will be revealed through comparative genomics analyses of human and zebrafish
BRCA2-associated cancers. In vivo characterization of these candidate genes in zebrafish will provide insight
into how they modulate cellular events of direct relevance to cancer development, and will guide initiation of
stable transgenic and mutant zebrafish lines for use in future carcinogenesis studies. Our long-term goal is to
define key conserved combinatorial gene disruptions and novel molecular pathways that drive cancer
progression. This K01 Research Career Award recipient is a DVM/PhD. scientist with board certification in
Veterinary Anatomic Pathology. The K01 research project was performed at North Carolina State University,
College of Veterinary Medicine (years 1-3), under the mentorship of Dr. Robert Smart, Dr. Matthew Breen, and
Dr. Jeffrey Yoder, and is currently being performed at the Ohio State University, College of Veterinary Medicine
under the mentorship of Dr. Ramesh Ganju (OSU Comprehensive Cancer Center) and continued mentorship of
Drs. Smart, Breen, and Yoder. The candidate is committed to a career in biomedical research, and seeks the
additional training, mentorship, and protected research time provided by this research and career development
plan to facilitate her transition to an independent academic career.

## Key facts

- **NIH application ID:** 10409852
- **Project number:** 3K01OD021419-05S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Heather R. Shive
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $96,808
- **Award type:** 3
- **Project period:** 2021-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409852

## Citation

> US National Institutes of Health, RePORTER application 10409852, Identification of genetic collaborators in cancer with a brca2-mutant zebrafish model (3K01OD021419-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10409852. Licensed CC0.

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