Fibroid, Leiomyoma
Conditions
Keywords
Senescent cells, Fibroids, Leiomyomas
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.
Interventions
None listed
Sponsors
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Johns Hopkins University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must be women above the age of ≥18 - ≤55 years. * Women with suspected uterine fibroids. * Subject must be or have been sexually active or have had a previous vaginal exam that used a speculum. * 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
* Unwilling to sign the consent form or complete questionnaire. * Pregnancy. * Cancer of the uterus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Develop an atlas to comprehensively quantify the rate of senescent cell (SnC) types in fibroid and myometrium tissue samples | 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
| Measure | Time frame | Description |
|---|---|---|
| Validate the concentration 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 |
| Rate of inhibition of cellular proliferation and ECM deposition by senolytics and senomorphics in fibroids | 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). |
Countries
United States
Contacts
Primary ContactJames Segars, MD
Backup ContactBhuchitra Singh, MD, MPH, MBA
Outcome results
None listed