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Biological Roles of Forkhead Box C1 in Pelvic Endometriosis

Award Number: F32HD104478
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/02/2020
PERIOD OF PERFORMANCE END DATE: 01/02/2022

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Biological Roles of Forkhead Box C1 in Pelvic Endometriosis - PROJECT SUMMARY Endometriosis is a chronic, estrogen-dependent gynecological disorder affecting 10-15% of reproductive age women which is characterized by the presence of endometrial tissue outside the uterus, predominantly in the pelvic peritoneum, and resulting in pelvic pain and infertility. The long-term goal of this research is discovery of molecular mechanisms governing the pathogenesis of endometriosis, particularly fibrosis, for development of non-invasive diagnostics and fertility-sparing treatments. Lesion etiology is difficult to study in women because of the significant delays of 8-11 years from the onset of disease to diagnosis and variations in disease progression. Over the past 25 years the Fazleabas lab has developed the baboon as an appropriate model to examine the establishment and progression of endometriotic lesions. FOXC1 was identified as a major upstream regulator of differentially expressed genes in lesions compared to matched endometrium from transcriptomic analyses. FOXC1 gain-of-function is associated with tissue remodeling and mechanisms of fibrosis, a hallmark of endometriotic lesions hypothesized to be crucial to the underlying pathogenesis of lesions. Thus, increased expression of FOXC1 may be an important contributor to the development of fibrosis in endometriotic lesions. We hypothesize that increased FOXC1, as a consequence of transcriptional and post-transcriptional regulation, alters the function of epithelial and stromal cells to promote fibrosis in the ectopic endometrium. We will determine the transcriptional and post-transcriptional mechanisms that regulate the increased expression of FOXC1 in endometriotic lesions (Aim 1), and the effects of FOXC1 expression on epithelial to mesenchymal (EMT) and fibroblast to myofibroblast (FMT) transitions, two components that contribute to fibrosis in endometriotic lesions. The proposed studies will provide key insight into the regulation and downstream effects of increased FOXC1 expression to uncover critical mechanisms in the pathogenesis of fibrosis in endometriotic lesions. The technical experience from these studies and career training from my sponsor and co-sponsors will prepare me for a successful independent research career for investigating endometriosis and disorders of the female reproductive tract to improve human health.


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: 2023 ( Subtotal = $0 )
2023	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	1	5/15/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	001	1	3/18/2022	SUPPLEMENT FOR EXPANSION	$33,195
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	003	1	5/24/2022	SUPPLEMENT FOR EXPANSION	-$33,195
2022	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	1	3/15/2022	NEW	$0
2022	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	002	1	5/24/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $66,390 )
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	001	1	2/10/2021	NEW	$1,080
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	1	12/2/2020	NEW	$65,310
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	002	1	2/10/2021	NEW	$0
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	003	1	4/27/2021	NEW	$0
														Subtotal = $66,390

Grand Total All Awards = $66,390

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Biological Roles of Forkhead Box C1 in Pelvic Endometriosis

Award Number: F32HD104478

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/02/2020

PERIOD OF PERFORMANCE END DATE: 01/02/2022

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