Tuesday, July 1, 2025 7/1/2025

Regulation of mechanosensitive ion channels by membrane lipids

Award Number: R01GM133845
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: 08/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2024

Group Awards By:

View Award Description

Regulation of mechanosensitive ion channels by membrane lipids - Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. Piezo channels mediate mechanoelectrical transduction to regulate crucial physiological processes, including vascular architecture and remodeling, cell migration, erythrocyte volume, touch, vibration, and proprioception. Piezo1 and Piezo2 are essential proteins in mice, as global knockouts are embryonic lethal and cell-specific knockouts result in animals with severe defects. In humans, Piezo channels gain- and loss-of-function mutations have been associated with hereditary human pathophysiologies. Mutations in Piezo1 are associated with dehydrated hereditary stomatocytosis, a hemolytic anemia characterized by increased cation permeability and dehydrated erythrocytes. Hence, it is essential to determine the proteins and lipids that regulate Piezo channels gating mechanisms. It has been shown that phosphoinositides and phosphatidylserine translocation regulate Piezo channels activity. However, it remains largely unknown how dietary fatty acids-containing phospholipids modulate Piezo1 and Piezo2 mechanical gating. Our long-term goal is to determine the mechanisms underpinning how bioactive lipids modulate mechanosensitive ion channels. In this proposal, the overall objective is to establish the molecular basis underlying Piezo channels modulation by dietary fatty acids. The central hypothesis is that Piezo channels activation and inactivation are regulated by the mechanical properties of the membrane via lipid remodeling. The rationale for the proposed research plan is that once the precise mechanisms are determined whereby fatty acids modulate Piezo channels function, it will be possible to use fatty acids to control vascular function and ameliorate the effects of hereditary disorders. The hypothesis will be tested by pursuing three Specific Aims: 1) Determine how fatty acid composition modulates Piezo1 activity through changes in membrane stiffness; 2) Determine the effect of dietary fatty acids on Piezo1 mutations causing red blood cell disorders; and 3) Test the hypothesis that saturated fatty acids decrease Piezo2 activation. We will leverage functional, biochemical, and biophysical approaches to uncover the contribution of bioactive lipids to mechanosensation. The research plan is innovative because it exploits the use of dietary fatty acids to control Piezo channels mechanical response. The proposed research is significant because it is expected to have broad translational impact in targeting Piezo channels, involved in vascular and neuronal function.


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 = -$33,105 )
2025	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	005	6	11/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$881
2025	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	004	6	10/28/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$5,020
2025	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	002	5	10/22/2024	NON-COMPETING CONTINUATION	-$1
2025	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	003	6	10/22/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$5,020
2025	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Trans-NIH Research Support	001	4	10/22/2024	SUPPLEMENT FOR EXPANSION	-$8,456
2025	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	000	4	10/22/2024	NON-COMPETING CONTINUATION	-$23,766
														Subtotal = -$33,105

Issue Date FY: 2024 ( Subtotal = $8,600 )
2024	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Biomedical Research and Research Training	001	6	12/14/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$335,399
2024	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	000	5	12/13/2023	NON-COMPETING CONTINUATION	-$326,799
														Subtotal = $8,600

Issue Date FY: 2023 ( Subtotal = $326,800 )
2023	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	000	5	6/12/2023	NON-COMPETING CONTINUATION	$326,800
														Subtotal = $326,800

Issue Date FY: 2022 ( Subtotal = $443,080 )
2022	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	000	4	6/28/2022	NON-COMPETING CONTINUATION	$326,800
2022	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Trans-NIH Research Support	001	4	6/29/2022	SUPPLEMENT FOR EXPANSION	$116,280
														Subtotal = $443,080

Issue Date FY: 2021 ( Subtotal = $443,080 )
2021	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Trans-NIH Research Support	000	2	4/26/2021	SUPPLEMENT FOR EXPANSION	$116,280
2021	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	001	3	6/9/2021	NON-COMPETING CONTINUATION	$326,800
														Subtotal = $443,080

Issue Date FY: 2020 ( Subtotal = $326,800 )
2020	2020	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	000	2	6/23/2020	NON-COMPETING CONTINUATION	$326,800
														Subtotal = $326,800

Issue Date FY: 2019 ( Subtotal = $326,800 )
2019	2019	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Biomedical Research and Research Training	000	1	7/16/2019	NEW	$326,800
														Subtotal = $326,800

Grand Total All Awards = $1,842,055

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of mechanosensitive ion channels by membrane lipids

Award Number: R01GM133845

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: 08/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer