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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HD111243 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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The investigators are evaluating the role of senescent cells in uterine fibroids.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Women with fibroids undergoing elective hysterectomy or myomectomy | Women between the age of 18-55 with fibroids undergoing elective hysterectomy or myomectomy |
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| Measure | Description | Time Frame |
|---|---|---|
| Develop an atlas to comprehensively quantify the rate of senescent cell (SnC) types in fibroid and myometrium tissue samples | 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. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Validate the concentration senescence-associated secretory profile (SASP) in cell cultures of senescent cells in uterine fibroids | Quantify levels of transcripts and proteins in the fibroid senescence-associated secretory profile (SASP) using ELISA and western blotting techniques | 5 years |
| Rate of inhibition of cellular proliferation and ECM deposition by senolytics and senomorphics in fibroids |
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Inclusion Criteria:
Exclusion Criteria:
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Women between the age of 18-55 years undergoing elective hysterectomy or myomectomy for uterine fibroids
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| James Segars, MD | Contact | 410-614-2000 | jsegars2@jhmi.edu | |
| Bhuchitra Singh, MD, MPH, MBA | Contact | 410-614-2000 | bsingh10@jhmi.edu |
| Name | Affiliation | Role |
|---|---|---|
| James Segars, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Recruiting | Baltimore | Maryland | 21287 | United States |
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| ID | Term |
|---|---|
| D007889 | Leiomyoma |
| ID | Term |
|---|---|
| D009379 | Neoplasms, Muscle Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Fibroid, myometrial samples, and peripheral blood sample.
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). |
| 5 years |