Hormonal influences on inflammation in endometriosis
Active Project Grant Awarded Last action
- Award ID
- R01HG013258
- Recipient
-
The University Of Texas Health Science Center At San Antonio UEI C3KXNLTAAY98
- Awarding agency
-
National Human Genome Research Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,349,313
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date 56% complete
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- San Antonio, TX 78229, USA
Award details come from USAspending.gov.
Description
- Abstract
- IT is estimated that around 10% of reproductive-age women of european ancestry, and 15% of women of asian ancestry are impacted by endometriosis. In endometriosis, glandular epithelium and stroma closely resembling the cells of the endometrium grow outside of the uterine cavity, evading the typical cell-intrinsic (programmed cell death) and cell-extrinsic safeguards (such as immune surveillance) that should prevent cells from surviving at ectopic locations. Endometriosis causes myriad symptoms including infertility, dysmenorrhea (menstrual cramps), deep dyspareunia (pain with deep penetration during sexual activity), dyschezia and dysuria (painful bowel movements and voiding), and chronic pelvic pain. Epidemiologic and genetic studies consistently find associations between endometriosis and inflammatory conditions such as asthma, irritable bowel syndrome and autoimmune disorders. Inflammation plays a central role in endometriosis, and the overarching hypothesis of this research is that studying risk loci shared by endometriosis and inflammatory conditions likely have a role for hormonal modulation, since endometriosis is an estrogen-driven disease. The goal of this proposal is to characterize key immune pathways that interact with hormonal responses in endometriosis. This will be achieved through large-scale population based genetic comorbidity studies and single cell systems biology methods to nominate shared risk genes and state-of-the-art single cell and spatial molecular profiling of follicular and luteal phase endometriosis. Key cell-cell signaling axes will be validated for their therapeutic potential using heterotypic in vitro and in vivo models of endometriosis. We will primarily focus on the proinflammatory IL1 pathway as a risk locus for endometriosis coincides with the IL1 gene family cluster. Based on integration of genome-wide risk data and single cell gene expression analysis of endometriosis we hypothesize that IL1A and/or IL1B expression by M2 macrophages combined with IL1 receptor expression in hormone-sensitive endometriosis epithelial cells is the pathway underlying risk at this locus. We will validate this hypothesis with multiomics and spatial profiling, and then dissect the roles of the key genes and cell populations using our existing state-of-the-art in vitro and in vivo models. This research will validate IL1 signaling as a key therapeutic target for endometriosis-associated inflammation, and will likely nominate additional candidates. Subsequent research will focus on clinical translation of these results. Endometriosis represents the ideal system to study hormonal regulation of inflammation, and pleiotropy, and so we expect that the impact of this study will extend to other inflammatory traits that are more common in women, and to the post-gwas field in general.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $171,386 | |
| Amendment | $67,472 | |
| Amendment | $168,929 | |
| Amendment | $229,419 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $397,447 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The University Of Queensland | $168,929 | |
| The University Of Queensland | $155,807 |
Quick answers
Who received award R01HG013258?
R01HG013258 was awarded to The University Of Texas Health Science Center At San Antonio by National Human Genome Research Institute (National Institutes of Health) on September 25, 2024.
How much is award R01HG013258 worth?
$1,349,313 has been obligated on R01HG013258.
Which agency awarded R01HG013258?
National Human Genome Research Institute (National Institutes of Health) awarded R01HG013258, with funding from Office of the Director (National Institutes of Health).
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