Role of Senescent Cells in Uterine Fibroid Pathogenesis
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.
Arms & interventions
Outcome measures
Primary
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.
Time frame: 5 years
Secondary
Validate the concentration senescence-associated secretory profile (SASP) in cell cultures of senescent cells in uterine fibroids
Time frame: 5 years
Rate of inhibition of cellular proliferation and ECM deposition by senolytics and senomorphics in fibroids
Time frame: 5 years
Eligibility criteria
Study locations (1)
Johns Hopkins Hospital
Baltimore, Maryland, 21287