# Functional analyses of super-enhancer dysregulation in colorectal carcinoma patient samples.

> **NIH NIH F30** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $50,028

## Abstract

PROJECT SUMMARY
Colorectal carcinoma (CRC) represents a malignancy that is among the highest in both cancer incidence and
mortality in men and women in the United States, yet disease remains dependent on cytotoxic therapies as
standard of care, highlighting a need for the identification of novel targets. We and other groups have
demonstrated extensive enhancer reprogramming in CRC; however, their biological impact on disease
progression remains unknown. Using a tissue ChIP-seq and RNA-seq approach on human CRC tumors and
matched normal epithelium, I found that enhancer reprogramming in CRC extends to the super-enhancer (SE)
landscape. The inclusion of an equal number of patient-matched normal colorectal crypt epithelium controls
identifies de novo formation of aberrant, tumor-specific super-enhancers as well as frequent loss of physiologic
normal-specific SEs with high recurrence across my cohort of samples. Super-enhancers are well-described to
selectively regulate key cell identity genes including proto-oncogenes in malignant cells—their profiling is an
established framework in target discovery in many difficult to treat cancers through leveraging epigenomic
dysregulation. Thus, our preliminary findings have unique implications for CRC biology. In this proposal, I seek
to elucidate a function for top recurrently gained and lost super-enhancers in CRC tumors. I will test the
hypothesis that perturbing both SEs and putative regulated genes will affect proliferation and invasion in CRC
using in vitro and colon organoid driven in vivo models. Findings from the proposed project will advance
knowledge in the field of how the active regulatory landscape in CRC tumors contributes to tumorigenesis,
promoting novel avenues of investigation and therapeutic targeting.

## Key facts

- **NIH application ID:** 10440355
- **Project number:** 5F30CA243207-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Royce Zhou
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $50,028
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440355

## Citation

> US National Institutes of Health, RePORTER application 10440355, Functional analyses of super-enhancer dysregulation in colorectal carcinoma patient samples. (5F30CA243207-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10440355. Licensed CC0.

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