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Role of TRPM8 in Cold-stored Platelet Transfusions

Award Number: R01HL153072
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Role of TRPM8 in Cold-stored Platelet Transfusions - PROJECT SUMMARY The detection of temperature change by nerve receptors in human tissues is a life‐preserving function which is highly evolutionarily selected. Platelets show a unique response to cold with cytoskeletal rearrangement and low‐level receptor activation. Temperature‐gated transient receptor potential channels (Thermo TRPs) are a family of ion channels activated by temperature. Transient Receptor Potential Melastatin 8 (TRPM8) also known as Cold and Menthol Receptor 1 (CMR1), is a nonselective cation channel gated by cold‐stimuli and various cooling reagents including menthol, eucalyptol, and icilin. In preliminary studies, we show that platelets express TRPM8, and the addition of TRPM8 agonists mimic typical morphologic and functional changes of platelets exposed to cold. The overarching goal of these studies is to characterize the molecular pathways through which platelets react to temperature changes. Further elucidating these mechanisms could lead to improved platelet storage conditions at 4ºC for transfusions, safer antiplatelet therapy, better prevention of heart attacks, and fewer side effects when therapeutic lowering of the body temperature after cardiac arrest is required. In aim 1 of this proposal, we will characterize the role of TRPM8 in platelets and elucidate its specific function for the cold platelet phenotype. This aim proposes to expand on our preliminary data that identified TRPM8 on human platelets and underscore its functional relevance. In aim 2 we will evaluate TRPM8 as a target for inhibition during platelet storage at 4ºC utilizing a small molecule TRPM8 inhibitor. In aim 3 of this proposal, we will determine the role of TRPM8 inhibition during 4ºC storage for recovery, survival, and function after transfusion in healthy human subjects.


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: 2024 ( Subtotal = $586,949 )
2024	2024	BLOODWORKS	921 TERRY AVE	SEATTLE	WA	98104	KING	USA	Blood Diseases and Resources Research	000	5	7/15/2024	NON-COMPETING CONTINUATION	$586,949
														Subtotal = $586,949

Issue Date FY: 2023 ( Subtotal = $598,928 )
2023	2023	BLOODWORKS	921 TERRY AVE	SEATTLE	WA	98104	KING	USA	Blood Diseases and Resources Research	000	4	8/31/2023	NON-COMPETING CONTINUATION	$598,928
														Subtotal = $598,928

Issue Date FY: 2022 ( Subtotal = $477,739 )
2022	2022	BLOODWORKS	921 TERRY AVE	SEATTLE	WA	98104	KING	USA	Blood Diseases and Resources Research	000	3	7/26/2022	NON-COMPETING CONTINUATION	$477,739
														Subtotal = $477,739

Issue Date FY: 2021 ( Subtotal = $477,739 )
2021	2021	BLOODWORKS	921 TERRY AVE	SEATTLE	WA	98104	KING	USA	Blood Diseases and Resources Research	000	2	7/15/2021	NON-COMPETING CONTINUATION	$477,739
														Subtotal = $477,739

Issue Date FY: 2020 ( Subtotal = $507,279 )
2020	2020	BLOODWORKS	921 TERRY AVE	SEATTLE	WA	98104	KING	USA	Blood Diseases and Resources Research	000	1	7/31/2020	NEW	$507,279
														Subtotal = $507,279

Grand Total All Awards = $2,648,634

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Role of TRPM8 in Cold-stored Platelet Transfusions

Award Number: R01HL153072

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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