Role of Senescent Cells in Uterine Fibroid Pathogenesis (SOUL Study)
Study Details
Study Description
Brief Summary
The investigators are evaluating the role of senescent cells in uterine fibroids.
Detailed Description
Uterine fibroids are prevalent tumors of uterus characterized by excessive fibrotic tissues. Using new cutting-edge computational methods, the investigators have found that small groups of senescent cells in fibroids work in concert with immune cells to produce soluble factors in fibroid tissues to create a feed-forward loop leading to fibrosis. This project seeks to unravel key cell-cell communication networks involving senescent and immune cells in fibroids to develop new treatments for uterine fibroids.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Women with fibroids undergoing elective hysterectomy or myomectomy Women between the age of 18-55 with fibroids undergoing elective hysterectomy or myomectomy |
Outcome Measures
Primary Outcome Measures
- A comprehensive fibroid and myometrium atlas that will enable us to predict the key senescent cell (SnC) types in fibroids and define their contribution to fibrosis [5 years]
Perform scRNASeq on human fibroids and control myometrium tissue and apply transfer learning algorithm for SnC identification and phenotyping to identify cell-cell communication patterns in fibroids versus control myometrial tissue using Domino to validate computationally predicted senescent cell types. The computationally predicted immune phenotypes will be validated with flow cytometry.
Secondary Outcome Measures
- Validate the senescence-associated secretory profile (SASP) in cell cultures of senescent cells in uterine fibroids [5 years]
Quantify levels of transcripts and proteins in the fibroid senescence-associated secretory profile (SASP) using ELISA and western blotting techniques
- Senolytics and senomorphics to inhibit cellular proliferation and ECM deposition [5 years]
Examine the in-vitro effects of senotherapeutcis using leiomyoma culture models and in mouse models. Measured by inhibition of proliferation, induction of apoptosis, inhibition ECM deposition, decrease in SnCs (senolytics) and senescence-associated secretory profile SASPs (senomorphics).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects must be women above the age of ≥18 - ≤55 years.
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Women with suspected uterine fibroids.
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Subject must be or have been sexually active or have had a previous vaginal exam that used a speculum.
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Subject must be able to understand, read and speak English or Spanish and subsequently, be able to understand what she is consenting to in terms of procedures and use/disclosure of protected health information.
Exclusion Criteria:
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Unwilling to sign the consent form or complete questionnaire.
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Pregnancy.
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Cancer of the uterus
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Johns Hopkins Hospital | Baltimore | Maryland | United States | 21287 |
Sponsors and Collaborators
- Johns Hopkins University
- National Institutes of Health (NIH)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
- Principal Investigator: James Segars, MD, Johns Hopkins University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00359032
- 1R01HD111243