Wednesday, July 2, 2025 7/2/2025

PHARMACOLOGICAL MODULATION OF PIEZO1 CHANNELS

Award Number: R01GM130834
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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PHARMACOLOGICAL MODULATION OF PIEZO1 CHANNELS - Summary Mechanosensitive Piezo ion channels enable eukaryotic cells to sense mechanical forces. In vertebrates, two Piezo homologs, Piezo1 and Piezo2, play central roles in all major physiological systems and are associated with numerous diseases including hypertension, xerocytosis, lymphedema, arthrogryposis, inflammation, pain, and cancer progression. Hence, pharmacological modulation of specific Piezo homologs could help treat many human ailments. Yet, this effort is currently limited by the paucity of homolog-selective pharmacological agents and the lack of a clear molecular understanding by which Piezo channels open and close their pore in response to physical and chemical stimuli. To bridge this gap, this proposal will leverage a recently identified pharmacological binding site in mammalian Piezo1 channels. Specifically, we will use reverse genetics, high-resolution electrophysiology, and calcium imaging to dissect structural pathways by which the binding of the small molecule Yoda1 energetically promotes an open state (Aim 1). In parallel, we will deploy an innovative, multi-pronged approach combining binding free energy calculations, structure-activity relationships, machine learning-based virtual screening of ultra- large billion-compounds library, and rapid experimental screening assays to identify novel molecules that preferentially bind conducting or non-conducting channel conformations, thus potentially acting as Piezo1 activators and inhibitors, respectively (Aim 2). Successful completion of this project will identify discrete mechanotrasnduction pathways associated with pharmacological activation of Piezo1 channels and identify novel pharmacological activators and inhibitors of Piezo1 channels with potential research and clinical value.


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 = $367,686 )
2025	2025	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	5/16/2025	NON-COMPETING CONTINUATION	$367,686
														Subtotal = $367,686

Issue Date FY: 2024 ( Subtotal = $367,685 )
2024	2024	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	003	6	5/23/2024	NON-COMPETING CONTINUATION	$367,685
2024	2023	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	002	5	5/17/2024	COMPETING CONTINUATION	$0
2024	2023	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	001	5	4/29/2024	COMPETING CONTINUATION	$166,085
2024	2022	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	4/29/2024	NON-COMPETING CONTINUATION	-$166,085
														Subtotal = $367,685

Issue Date FY: 2023 ( Subtotal = $373,201 )
2023	2023	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	001	5	8/18/2023	COMPETING CONTINUATION	$373,201
2023	2022	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	8/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $373,201

Issue Date FY: 2022 ( Subtotal = $324,300 )
2022	2022	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	5/18/2022	NON-COMPETING CONTINUATION	$324,300
														Subtotal = $324,300

Issue Date FY: 2021 ( Subtotal = $432,834 )
2021	2021	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	5/20/2021	NON-COMPETING CONTINUATION	$324,300
2021	2021	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	001	3	7/13/2021	SUPPLEMENT FOR EXPANSION	$108,534
														Subtotal = $432,834

Issue Date FY: 2020 ( Subtotal = $301,668 )
2020	2020	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	5/18/2020	NON-COMPETING CONTINUATION	$301,668
														Subtotal = $301,668

Issue Date FY: 2019 ( Subtotal = $301,668 )
2019	2019	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	9/4/2019	NEW	$301,668
														Subtotal = $301,668

Grand Total All Awards = $2,469,042

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PHARMACOLOGICAL MODULATION OF PIEZO1 CHANNELS

Award Number: R01GM130834

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/05/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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