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Cytoskeletal regulation of the Hippo and Notch1 signaling pathways in endometrial stromal cell decidualization and endometriosis

Award Number: F31HD107923
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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PROJECT SUMMARY Endometrial stromal cell decidualization is critical to reproductive success. The decidualization process involves morphological and functional changes of endometrial stromal cells. The actin-myosin cytoskeleton contributes to changes in cell morphology and likely plays a role in the intracellular shuttling of proteins critical in decidualization. Decidualization is the terminal differentiation of human endometrial stromal cells in response to rising progesterone levels and is maintained throughout pregnancy by embryonic signals and progesterone. Defects in this process are associated with reproductive failure in diseases such as endometriosis. Endometriosis is characterized by endometrial-like tissue found at ectopic sites and the disease is associated with significant pelvic pain, infertility, and dysmenorrhea, but its pathophysiology remains elusive. The aim of this proposal is to understand the functional role of the cytoskeleton in the decidualization process and determine how this is aberrant in the stromal cells of women with endometriosis which may contribute to their infertility. The Hippo target homologs, YAP and TAZ, and Notch1 signaling are known to mediate the initiation of the decidualization response, but what regulates these pathways during decidualization remains unknown. Previous research has also shown that significant changes in the cytoskeleton are associated with endometrial stromal cell decidualization. In addition, cytoskeleton dynamics and Notch1 and YAP/TAZ signaling are dysregulated in endometriosis. We hypothesize that the cytoskeleton mediates the decidualization response and is defective in infertile women with endometriosis. To test our overall hypothesis in Aim 1 we will investigate direct actin-myosin cytoskeleton regulation of the Hippo/YAP/TAZ and NOTCH1 signaling pathways in the context of endometrial stromal cell decidualization and in Aim 2, we will determine how an altered cytoskeleton compromises decidualization in stromal cells from infertile women with endometriosis. The proposed studies will address cytoskeletal regulation of key molecular mechanisms that regulate stromal cell decidualization. These studies will greatly expand the technical expertise in cell and molecular biology of the applicant. These experiences combined with professional development supported by the sponsor, co-sponsor, and program will help the applicant to develop the skill set required to pursue a career in basic science research.


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 = $40,001 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	2	1/25/2023	NON-COMPETING CONTINUATION	$39,059
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	001	2	2/10/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $40,001

Issue Date FY: 2022 ( Subtotal = $38,739 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	000	1	1/25/2022	NEW	$38,023
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	7/11/2022	NEW	-$1
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	1/25/2022	NEW	$0
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Child Health and Human Development Extramural Research	002	1	4/25/2022	NEW	$717
														Subtotal = $38,739

Grand Total All Awards = $78,740

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Cytoskeletal regulation of the Hippo and Notch1 signaling pathways in endometrial stromal cell decidualization and endometriosis

Award Number: F31HD107923

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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