# NSD1 Inactivation in Head and Neck Cancer

> **NIH NIH R00** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $249,000

## Abstract

PROJECT SUMMARY
Increasing evidence has supported a role for chromatin misregulation in the pathogenesis of various human
diseases including cancer, although the underlying mechanism remains unclear. Recent tumor genome
sequencing efforts have identified inactivating mutations in NSD1, a histone H3 lysine 36 (H3K36)-specific
methyltransferase, in 10-15% of head and neck squamous cell carcinomas (HNSCC), the sixth leading cancer
worldwide. This study focuses on elucidating the molecular mechanisms by which NSD1 inactivation facilitate
HNSCC development and will test the central hypothesis that biochemical and genetic inactivation of NSD1
alters DNA methylome and transcriptome to disrupt squamous tissue differentiation and promote HNSCC
initiation in vivo. During the mentored training period, I will characterize the biochemical basis and functional
importance of NSD1 inhibition by H3 lysine 36 to methionine (H3K36M) mutation, an oncohistone previously
associated with pediatric malignancies and identified in HNSCC through my preliminary studies. I will also
profile the impact of NSD1 and H3K36M mutations on the genome-wide distribution of H3K36 methylation and
DNA methylation as well as on the transcriptome. During the independent phase of the award period, I propose
to investigate the function of NSD1 in squamous tissue differentiation and in vivo suppression of HNSCC.
Together the proposed studies will provide novel insights into the pathogenesis of a subset of genetically
defined and epigenetically distinct HNSCC that can translate into improved care for patients. They will also
serve as a platform for me to obtain trainings in chemical biology, computational epigenomics and mouse
models of cancer that will critically contribute to my career development as an independent investigator in the
field of cancer epigenetics.

## Key facts

- **NIH application ID:** 9840467
- **Project number:** 5R00CA212257-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Chao Lu
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-01-15 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840467

## Citation

> US National Institutes of Health, RePORTER application 9840467, NSD1 Inactivation in Head and Neck Cancer (5R00CA212257-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840467. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*