# Stem cell reprogramming during oncogenesis and development

> **NIH NIH F32** · ROCKEFELLER UNIVERSITY · 2020 · $57,456

## Abstract

Project Summary:
Tissue stem cells are critical for the replenishment of dying cells and for wound-repair. Previous
studies have demonstrated that many cancers can arise from the dysfunction of stem cells,
either through accumulation of mutations, or more recently, aberrancies in the epigenetic
landscape. Sox9, a transcription factor, plays an important role in the development and
maintenance of many stem cell compartments. In the skin, Sox9 is essential for hair follicle
stem cells, while epidermal stem cells are characterized by lack of Sox9 expression.
Interestingly, basal cell carcinomas (BCC) overexpress Sox9, yet have been demonstrated to
arise from epidermal and not hair follicle stem cells. Moreover, Sox9 is critical for BCC as
genetic loss of Sox9 completely abolishes tumor formation in vivo. The mechanisms by which
ectopic Sox9 contributes to tumor formation for BCC and other cancers remain to be elucidated.
However, in HFs, Sox9 binds and regulates the key open chromatin domains (super-enhancers)
that choreograph stem cell genes, and my preliminary studies indicate that ectopic expression
of Sox9 in the adult epidermis shifts the chromatin landscape by activating previously silenced
genes that may be important for BCC transformation. Therefore, I hypothesize that Sox9 elicits
a fate switch in Epidermal stem cells by directly binding and remodeling chromatin at key
enhancers. Utilizing a newly developed transgenic mouse that expresses an inducible Sox9 in
the epidermal stem cells, I will map and annotate the chromatin and transcriptional changes that
occur after induction of Sox9 to pinpoint deviations from Sox9-negative epidermal and Sox9+
hair follicle stem cells. Exploiting a combination of nucleosome binding experiments,
immunoprecipitations and mass spectrometry, I will determine whether Sox9 can directly
recognize and remodel heterochromatin, or whether it achieves this through the interactions of
other proteins. Finally, using a powerful in utero lentiviral approach developed in the Fuchs lab, I
will functionally test the results of candidates identified using CRISPR/CAS in the context of
tumor formation and progression. My studies will directly further our knowledge regarding Sox9
mediated chromatin remodeling and subsequent activation of oncogenic and stem cell
transcriptional pathways. Identifying the key Sox9 target genes as well as the proteins involved
in epidermal to BCC reprogramming will lead to the development of novel therapeutics used to
“reset” the tumor epigenetic landscape into a non-malignant form.

## Key facts

- **NIH application ID:** 10218042
- **Project number:** 5F32CA221353-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Nicholas C Gomez
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $57,456
- **Award type:** 5
- **Project period:** 2017-07-15 → 2021-07-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218042

## Citation

> US National Institutes of Health, RePORTER application 10218042, Stem cell reprogramming during oncogenesis and development (5F32CA221353-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10218042. Licensed CC0.

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