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Piezo-1 & 2’s role in murine intestinal muscularis cells of the SIP syncytium

Award Number: R01DK132319
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Piezo-1 & 2’s role in murine intestinal muscularis cells of the SIP syncytium - This grant application aims to identify and characterize the role of Piezo in cells of the muscularis during baseline and stretched states. Bowel motility disorders and acute bouts of bowel obstruction are common clinical problems and can be severe, and we do not fully understand their mechanisms or have effective treatments. One crucial mechanism controlling bowel motility is mechanosensing, allowing each bowel segment to sense and respond to stretch. Various cell types within the intestinal muscularis control motility, sense stretch, and induce contractions. Among these cells are the components of the SIP syncytium comprised of smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and PDGFRcells. These cells respond to stretch and receive inputs from enteric neurons (EN), glia, and enteroendocrine cells (EEC) that modulate SIP syncytium activity. However, the mechanism underlying the ability to sense and respond to stretch has not been thoroughly evaluated. Here we propose to investigate the role of Piezo in this process. Piezo is a relatively new calcium channel that functions as a mechanosensor in numerous cells, including those in the gut. Here, we will focus on its role in smooth muscle cells, interstitial cells of Cajal, and PDGFRcells of the small intestine. To perform these experiments, we have developed novel methods to maintain murine cells of the muscularis in an in vitro system. We will also use physiologically tunable hydrogels to examine the consequences of stretch in this setting. Finally, we will use various genetic approaches to explore the effects of mechanosensing in SIP cells of the gut. After this study, we anticipate that we will further elucidate the biomechanical and physiological consequences of disrupting a mechanosensitive channel that alters muscularis function and highlight myopathy's indirect effect on the adjacent epithelial layer to exacerbate the dysmotility further.


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: 2026 ( Subtotal = $750,172 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/16/2026	NON-COMPETING CONTINUATION	$750,172
														Subtotal = $750,172

Issue Date FY: 2025 ( Subtotal = $674,937 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/20/2025	NON-COMPETING CONTINUATION	$674,937
														Subtotal = $674,937

Issue Date FY: 2024 ( Subtotal = $719,703 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/1/2024	NON-COMPETING CONTINUATION	$674,723
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/10/2024	NON-COMPETING CONTINUATION	$44,980
														Subtotal = $719,703

Issue Date FY: 2023 ( Subtotal = $749,460 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/20/2023	NEW	$749,460
														Subtotal = $749,460

Grand Total All Awards = $2,894,272

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Piezo-1 & 2’s role in murine intestinal muscularis cells of the SIP syncytium

Award Number: R01DK132319

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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