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Functional Genomics Across an Ethnically and Racially Diverse Endometriosis Population

Award Number: R01HD113693
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/16/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Functional Genomics Across an Ethnically and Racially Diverse Endometriosis Population - ABSTRACT Around 10% of reproductive-age women have endometriosis, although prevalence is thought to differ by ancestry, with rates the highest in Asians where around 15% of women are affected. The molecular drivers of this common chronic gynecologic condition are poorly understood, particularly in non-Whites. Endometriosis is a major cause of pain and infertility in women, is associated with significant financial burden, and multiple comorbidities including pain syndromes, inflammatory and immune conditions, anxiety, and depression. Endometriosis lesions frequently harbor somatic mutations in “driver” genes such as KRAS, PIK3CA and ARID1A, but the consequences of these mutations are poorly understood. The goal of this proposal is to leverage a deeply annotated collection of specimens from >1,400 endometriosis patients to catalogue the spectrum of of somatic mutations in endometriosis across White, Asian, Black and Hispanic Women and to use state-of-the-art single cell and spatial genomics technologies to identify therapeutic opportunities associated with specific mutations. Aim 1 will use exome and targeted sequencing to map population-specific frequencies of somatic drivers. Aim 2 will profile endometriosis and eutopic endometrium tissues using single cell transcriptomic and epigenomic analyses and spatial transcriptomics to map the cellular and molecular impacts of somatic mutations to identify therapeutic targets. Aim 3 will use an orthotopic syngeneic mouse model of endometriosis to validate the mechanisms by which mutations impact endometriosis formation and persistence and to test therapeutics tailored to the genetic alterations in the lesions. Genes and pathways we discover to be associated with somatic mutation of ARID1A, KRAS and other genes in endometriosis represent novel opportunities for diagnosis and personalized treatment based on the specific landscape of a woman’s disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $558,588 )
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Child Health and Human Development Extramural Research	000	3	12/5/2024	NON-COMPETING CONTINUATION	$502,730
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Child Health and Human Development Extramural Research	003	3	4/16/2025	NON-COMPETING CONTINUATION	$55,858
2025	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	1	3/18/2025	NEW	-$1
2025	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Child Health and Human Development Extramural Research	002	2	3/18/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
														Subtotal = $558,588

Issue Date FY: 2024 ( Subtotal = $607,398 )
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	1	7/29/2024	NEW	-$607,396
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	12/27/2023	NEW	$607,397
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Child Health and Human Development Extramural Research	002	2	7/29/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$607,397
														Subtotal = $607,398

Grand Total All Awards = $1,165,986

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Functional Genomics Across an Ethnically and Racially Diverse Endometriosis Population

Award Number: R01HD113693

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/16/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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