# REST/NRSF, miRNAs, and tissue remodeling in adenomyosis pathophysiology

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $633,243

## Abstract

Project Summary
 Adenomyosis is a nonmalignant uterine disease characterized by endometrial stroma and glands found
within the myometrium. Adenomyosis has been associated with heavy and painful menstrual periods, pelvic
pain, pain with intercourse, and reproductive dysfunction. However, now that imaging is identifying
adenomyosis in younger and more varied women than those electing hysterectomy where pathological
diagnosis occurred, many of our assumptions about the clinical disease are changing. Additionally, the only
widely accepted and effective treatments for adenomyosis, hysterectomy and hormonal suppression, are
unacceptable for this wider group of women. Much of our uncertainty on diagnosis and treatment for
adenomyosis stem from our uncertainty on its' pathogenesis. The most common theory of adenomyosis
development centers on the involvement of tissue injury and repair mechanisms with resulting adenomyosis
development from invagination of the endometrial basalis into the myometrium (the invasion/invagination
theory). While emerging data support a role for this theory and the involvement of cell migration, proliferation
and invasion in adenomyosis development, a detailed understanding on the mediators and mechanisms is
clearly lacking. To fill this critical gap in our knowledge we will perform a series of experiments which integrate
well-defined human specimens, novel mouse models and rigorous in vitro approaches to identify key
components of a REST-miRNA-tissue remodeling cascade and demonstrate the functionality of this pathway in
the pathogenesis of adenomyosis. The specific hypothesis to be tested in this application is that reduced
expression of endometrial and/or myometrial REST induces alterations in a miRNA-mediated tissue
remodeling cascade which augments adenomyosis development. To test this hypothesis, we will delineate
expression of a novel REST-miRNA mediated tissue remodeling pathway in adenomyosis and define REST's
function using novel experimental mouse models. Using in vitro models for cell proliferation, migration and
invasion, we will decipher cell to cell communication between myometrial-endometrial REST-miRNA tissue
remodeling pathway signaling relevant to adenomyosis pathophysiology. Together, these experiments will
provide novel insight into the role of REST in adenomyosis development and in turn, may lead to identification
of novel treatment targets for this disease.

## Key facts

- **NIH application ID:** 10465223
- **Project number:** 5R01HD105714-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Vargheese Mani Chennathukuzhi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $633,243
- **Award type:** 5
- **Project period:** 2021-08-09 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465223

## Citation

> US National Institutes of Health, RePORTER application 10465223, REST/NRSF, miRNAs, and tissue remodeling in adenomyosis pathophysiology (5R01HD105714-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465223. Licensed CC0.

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