# Patient-specific targeting of uterine fibroids

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $431,991

## Abstract

Project Summary
Uterine leiomyomas (fibroids) are the most common tumors found in reproductive aged women, with an overall
prevalence of up to 75% by age fifty. Patients with a clinically significant fibroid burden can have multiple
debilitating symptoms, making fibroids the leading indication for hysterectomy in the United States. There is a
strong racial disparity in the disease, with African-American women presenting with an earlier onset of the
disease, with greater severity, and having a prevalence of 89% by the age of fifty. The etiology of the disease
is largely unknown, but recent discoveries that the MED12 gene is mutated in 50-70% of fibroids and that
introduction of a similar mutation in mouse uteri can lead to fibroids suggest that mutant MED12 may be a key
player in the etiology of uterine fibroids. However, the actual mechanisms driving the disease, in either MED12
mutant fibroids or MED12 wildtype fibroids, are unknown. This gap in knowledge has hindered the
development of effective therapies that obviate the need for women to have hysterectomies. We propose to
exploit next generation sequencing to perform comprehensive analyses of the epigenetic, genomic, and
transcriptional landscape of different subsets of uterine fibroids for comparison with normal myometria. We will
also compare fibroids from caucasian and African-American women to try to understand the disparity in the
disease between these two populations, which are not currently associated with any highly significant genetic
mutations. We have assembled a team of experts for tissue processing and assays, next generation
sequencing, and bioinformatic analyses and have performed preliminary studies that have led us to
hypothesize that a fibroid subtype-specific precision medicine approach is needed for women with symptomatic
disease. We will validate our preliminary results in a larger and more diverse cohort of women with greater
depth and determine whether elevated serum levels of characteristic proteins we have determined are highly
expressed in specific subsets of fibroids could be used as serum biomarkers for the disease. We will perform
in vitro and in vivo experiments to understand the mechanisms and pathways disrupted by their
overexpression. We will use the HumanMethylation (850k/EPIC) DNA methylation array to establish whether
methylation differences among the fibroid subtypes contribute to the differential expression by RNA-seq.
Chromatin immunoprecipitation sequencing (ChIP-Seq) will be done between MED12 mutant and HMGA2
overexpressing fibroids and myometrial cells to compare and contrast differential binding of these chromatin
modifying proteins. We will use ATAC-seq to determine open chromatin regions in the tissues of the fibroid
subtypes and correlate with RNA-seq. We will be analyzing both broad and deep data to provide a better
understanding of combined RNA-seq, epigenetics, and genomic landscapes found in subsets of uterine
fibroids. We expect that these s...

## Key facts

- **NIH application ID:** 10401333
- **Project number:** 5R01HD096259-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** JOSE M. TEIXEIRA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $431,991
- **Award type:** 5
- **Project period:** 2019-08-29 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401333

## Citation

> US National Institutes of Health, RePORTER application 10401333, Patient-specific targeting of uterine fibroids (5R01HD096259-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10401333. Licensed CC0.

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