# Northwestern Uterine Leiomyoma Research Center

> **NIH NIH P50** · NORTHWESTERN UNIVERSITY · 2021 · $1,466,650

## Abstract

Uterine leiomyoma (LM, fibroids) are the most common tumor in women, disproportionately affect African-
Americans, and cause irregular uterine bleeding and anemia, necessitating more than 200,000 hysterectomies
annually in the US. Our long-term objective is to understand novel clinically relevant and medically targetable
mechanisms responsible for the pathogenesis and growth of uterine LM in order to reduce associated
morbidity. We propose and request funds to support the Northwestern Uterine Leiomyoma Research
Center, comprising three highly coordinated and synergistic Research Projects, an Administrative Core and an
Education and Outreach Core. Two mutually exclusive key driver somatic mutations (mut-) or rearrangements
(-ra) affecting the MED12 and HMGA2 genes have been found in 85% of all LM, but the underlying
mechanisms that cause tumorigenesis and tumor growth remain unknown. We propose to ascertain the effects
of mut-MED12 and HMGA2-ra on epigenomic programming of LM cells, LM stem cell (LSC) function,
development of heterogenic cell populations in these tumors, and genome-wide progesterone (P4) action. We
will use cutting-edge in vivo models and high-throughput technologies to uncover novel mechanisms and
identify genotype-specific therapeutic targets for developing precision medical treatments for LM. Project 1
(Bulun/Yin/Dai) will test the hypothesis that mut-MED12 alter genome-wide progesterone receptor (PR)-
chromatin interaction signatures and associated histone modifications, thereby enhancing P4 action in the LM
intermediate cell population (LICs), which provides a support niche for LSC survival and proliferation. Project 2
(Rajkovic) will test the hypothesis that distinct driver mutations affecting MED12 and HMGA2 determine cellular
and molecular heterogeneity during LM tumorigenesis. Through cell fate tracing studies, we will determine
whether mut-MED12 cells give rise to different cell populations in the myometrium that drive the formation of
LM. Project 3 (Chakravarti/Wei) will test the hypothesis that overexpression of HMGA2 in LM alters 3D
chromatin interactions and the epigenome to modify the development, progression, and therapeutic response
of LM. As model systems, we will use LM tissues, antibody-sorted human LM cell populations and a human-
equivalent mouse model of LM with mut-MED12 in uterine tissue. The Education and Outreach Core will
support research activities performed within and across the Center by developing communication, outreach,
and education strategies to promote health equity and eliminate disparities in LM, engaging the general public,
students in the Chicago area, and the scientific and medical community. The Administrative Core will ensure
that the Center achieves its aims and will synergize the individual Research Projects with the work of the
Education-Outreach Core and other institutional cores; it will also solicit and coordinate the review of Pilot
Projects. We anticipate that our synergistic app...

## Key facts

- **NIH application ID:** 10153840
- **Project number:** 5P50HD098580-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Serdar E. Bulun
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,466,650
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153840

## Citation

> US National Institutes of Health, RePORTER application 10153840, Northwestern Uterine Leiomyoma Research Center (5P50HD098580-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153840. Licensed CC0.

---

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