# Leveraging the epigenome of inflammatory bowel disease to gain mechanistic insights into disease pathophysiology”

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $191,280

## Abstract

Contact PD/PI: Kugathasan, Subra
PROJECT SUMMARY/ABSTRACT
Ulcerative colitis (UC) is a chronic relapsing and remitting intestinal inflammatory disorder with a very
heterogeneous clinical course. While on life-long maintenance therapy, although most patients achieve complete
mucosal healing with no disease activity during the course of treatment of UC, a subgroup (~40%) experience
chronically active severe disease with persistent inflammation as reflected by need for escalation of medical
therapy or surgery. The reasons underlying such differential clinical course/disease severity are not well
understood. Cross-sectional studies of DNA methylation, a key regulator of gene expression and molecular
phenotype, have begun to reveal epigenetic associations with UC. However, owing to the dynamic plasticity of
DNA methylation and UC disease behavior, it is critical to understand the temporal relationship between the
methylome and the disease in order to establish the direction of causality and leverage the epigenome for
therapeutic benefits. Here we hypothesize that, longitudinal framework – having DNA methylation data and well
documented disease measures collected concurrently during the disease onset and at later time – supplemented
by genetic association and the concept of Mendelian randomization, can help identify methylation changes that
causally underlie disease pathology. Herein, using methylation data generated from DNA derived from the
disease-relevant tissue, rectal mucosa, obtained at two time points – at diagnosis and 1 year follow-up – from
participants in the PROTECT cohort, a pediatric prospective inception UC cohort, we plan to (i) identify DNA
methylation changes that causally influence the development of UC, and modify its phenotypic expression and
severity; and (ii) integrate these methylation data with prior genotype and gene expression data in order to
elucidate the functional consequence of disrupted methylation patterns and to gain insights into molecular
underpinnings of UC. In completion, the results of this project will provide new insights into the epigenetic basis
of UC. Understanding the temporal relationship between how methylome changes during the course of the
disease, as a result of varying clinical characteristics, and how disease subgroups evolve may aid in the
identification of potentially causal epigenetic targets which could subsequently be leveraged for therapeutic
benefits.

## Key facts

- **NIH application ID:** 10018884
- **Project number:** 5R21DK119997-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** SUBRA KUGATHASAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,280
- **Award type:** 5
- **Project period:** 2019-09-17 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018884

## Citation

> US National Institutes of Health, RePORTER application 10018884, Leveraging the epigenome of inflammatory bowel disease to gain mechanistic insights into disease pathophysiology” (5R21DK119997-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018884. Licensed CC0.

---

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