# Investigating epigenetic mechanisms of cancer

> **NIH NIH R50** · UNIVERSITY OF FLORIDA · 2024 · $162,115

## Abstract

Project Summary
Disruptions of epigenetic mechanisms that regulate gene expression are frequently found in cancer and
collaborate with genetic alterations to drive cancer phenotypes such as therapy resistance and immune escape.
Since 2016, Dr. Bennett, the research specialist for this R50 award application, has supervised teams of
researchers and performed key experiments for the NCI-funded research program of the unit director, Dr.
Jonathan Licht, at the University of Florida Health Cancer Center to study how epigenetic mechanisms are
disrupted in cancer. Dr. Bennett has strong track record of important contributions to cancer research, and his
work has been instrumental to the success of CA195732, U54CA193419 and U01CA225566. He has
demonstrated that a glutamate to lysine mutation at amino acid 76 of histone H2B fundamentally alters chromatin
dynamics and accessibility, causing changes in gene expression and cell growth properties that favor
tumorigenesis. Dr. Bennett showed that treatment of acute lymphoblastic leukemia cells harboring mutant
histone methyltransferase NSD2 with PRC2 inhibitors can reactivate glucocorticoid (GC) receptor expression
and restore sensitivity of these cells to GC therapy. In addition, he has determined genetic dependencies for
growth and therapy resistance in uveal melanoma as well as identified an HDAC8-driven permanent lineage
switch maintained after drug withdrawal in melanoma. This R50 award will provide career stability for Dr. Bennett
to continue making important contributions to cancer research and advancing the unit director’s larger NCI-
funded research program. Dr. Bennett will lead research teams and perform key experiments to accomplish the
aims of the Dr. Licht’s three NCI-funded R01 awards: R01CA266078 (Histone fold Mutations in Cancer
Pathogenesis), multi-PI R01CA256193 (Characterization and targeting of the epigenetic state underlying uveal
melanoma liver metastasis) and multi-PI R01CA262483 (Defining and targeting epigenetic plasticity-driven drug
resistance and immune escape in melanoma). In addition, funding of this award will allow Dr. Bennett to pioneer
new directions for each project especially by applying cutting-edge technologies and building collaborations with
other NCI-funded investigators. Dr. Bennett is an expert in a wide spectrum of epigenomics techniques such as
biochemical assays, gene expression analysis, chromatin profiling and CRISPR screens that are essential for
the success of these awards and advancing the unit director’s NCI-funded cancer research program. These
studies will reveal new epigenetic mechanisms of oncogenesis that contribute to tumor progression,
heterogeneity, and therapy resistance, with the aim of finding new targets and pathways of intervention for cancer
patients that will ultimately lead to better patient outcomes.

## Key facts

- **NIH application ID:** 10977803
- **Project number:** 1R50CA293837-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Richard L Bennett
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $162,115
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977803

## Citation

> US National Institutes of Health, RePORTER application 10977803, Investigating epigenetic mechanisms of cancer (1R50CA293837-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10977803. Licensed CC0.

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