# Investigating the role of KLF5 genomic alterations in tumorigenesis

> **NIH NIH R00** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $243,715

## Abstract

PROJECT SUMMARY
Dr. Xiaoyang Zhang is a postdoctoral research fellow in the laboratory of Dr. Matthew Meyerson at Dana-
Farber Cancer Institute and the Broad Institute. His long-term career goal, in alignment with the mission of the
NCI, is to reduce cancer-associated mortality and suffering by determining mechanisms of cancer development
and identifying attractive therapeutic targets. To accomplish this goal, Dr. Zhang uniquely leverages both
genomics and cellular and molecular biology methods to answer fundamental questions relating to cancer
biology.
Large-scale genomic surveys of human cancer have recently found two types of genomic alterations of the
KLF5 gene. Dr. Zhang identified that a non-coding region, nearby the KLF5 gene and filled with super-
enhancers, is focally amplified in several cancer types and the amplification correlates with KLF5 over-
expression. In addition, Dr. Meyerson's laboratory identified significant hot-spot mutations in the DNA binding
domain of the KLF5 gene in non-small cell lung cancers. All these strongly suggest that KLF5 is a novel
oncogene. This proposal aims to characterize the role of these genomic alterations in regulating KLF5 activity
and promoting tumorigenesis. Aim 1 will study the link between the super-enhancer amplification and KLF5
over-expression, and the oncogenic consequences of KLF5 over-expression in diverse cancer types. Then,
Aim 2 will study the oncogenic function of KLF5 hot-spot mutations by using isogenic KLF5 wild-type and
mutant cell lines generated by genome-editing tools. Finally, in Aim 3, a CRISPR-mediated promoter/enhancer
screening will be developed to identify the functional binding sites of KLF5 mutants and their associated target
genes and pathways. The proposed research will improve our understanding of how oncogenic transcription
factors promote cancer development and may yield novel therapeutic targets.
Dr. Zhang will gain more research training in biostatistics, computational biology and genome-editing, and
simultaneously enhance his career development through training in grant-writing and leadership. The
outstanding research environment and facilities available to Dr. Zhang include laboratory space and full
institutional access at both Dana-Farber Cancer Institute and the Broad Institute. During the K99 phase, Dr.
Zhang's research and training will be carried out under the primary mentorship of Dr. Matthew Meyerson, a
leader in cancer genomics, and will be additionally enhanced by collaborations with experts in computational
biology and high-throughput genetic screening, as well as by mentoring from an advisory committee consisting
of Drs. Myles Brown, Bradley Bernstein, Feng Zhang, and Levi Garraway.

## Key facts

- **NIH application ID:** 9882969
- **Project number:** 5R00CA215244-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Xiaoyang Zhang
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,715
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882969

## Citation

> US National Institutes of Health, RePORTER application 9882969, Investigating the role of KLF5 genomic alterations in tumorigenesis (5R00CA215244-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9882969. Licensed CC0.

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