# A New Target for Chromatin Remodeler Defects in Cancer

> **NIH NIH R35** · BAYLOR COLLEGE OF MEDICINE · 2021 · $950,996

## Abstract

My laboratory has pioneered new research directions in environmental carcinogenesis for the
past 25 years. We identified new targets for chemical carcinogens, new functions for “old” tumor
suppressor genes, and elucidated the first mechanism by which environmental exposures during
development could reprogram the epigenome to increase cancer risk in adulthood. It is my goal
to continue to advance the field of cancer research by tackling challenging questions, rather than
performing incremental research, which while safe, does little to “move the needle”. My objective
for obtaining this R35 Outstanding Investigator Award is to focus my efforts on an exciting new
discovery, which represents a paradigm shift in how we look at chromatin remodeler defects in
cancer. As an unexpected off-shoot of our research on how environmental carcinogens reprogram
the epigenome, we discovered a new function for the cell’s epigenetic machinery, and a new way
for defects in chromatin remodeler genes to drive cancer. The Overarching Hypothesis for this
R35 application is that the coding machinery known for “reading, writing and erasing”
epigenetic methyl marks on chromatin plays a second, equally important but heretofore
unappreciated, coding function “reading, writing and erasing” methyl marks on the
cytoskeleton. We reported (Park et al Cell 2016), and support with additional Preliminary Data,
that many chromatin remodelers are actually dual-function proteins, participating in both the
Histone Code of chromatin, and the Tubulin Code of microtubules. This insight sets the stage for
a new paradigm, wherein the cell’s methylation machinery serves two coding functions, one on
chromatin and one on the cytoskeleton. It opens new frontiers for understanding how cells utilize
and regulate one machinery with two distinct, but equally important coding functions. This is of
special importance for cancer research, as we have been blind to the fact that defects in chromatin
remodeler genes can directly impact the cytoskeleton, for example, via mitotic spindle defects
that drive genomic instability and cytoskeletal defects that alter mobility to promote metastasis.
The experiments proposed in this application are designed to open new doors for understanding
the impact of chromatin remodeler defects in cancer, and for the development of therapies with
efficacy against both the epigenetic and cytoskeletal alterations caused by defects in genes that
encode dual-function chromatin-cytoskeleton remodelers.

## Key facts

- **NIH application ID:** 10216200
- **Project number:** 5R35CA231993-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Cheryl L. Walker
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $950,996
- **Award type:** 5
- **Project period:** 2018-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216200

## Citation

> US National Institutes of Health, RePORTER application 10216200, A New Target for Chromatin Remodeler Defects in Cancer (5R35CA231993-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10216200. Licensed CC0.

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