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Allostery of RAMP-CLR Signaling in Vascular Cells During Migraine

Award Number: R01HL176992
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/2026
PERIOD OF PERFORMANCE END DATE: 11/30/2030

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Allostery of RAMP-CLR Signaling in Vascular Cells During Migraine - Project Summary Abstract This proposal builds on our long-standing interest and expertise in the functions of the multifunctional G protein-coupled receptor (GPCR), calcitonin receptor-like receptor (CLR=protein; Calcrl=gene) and its allosteric modulators, receptor activity modifying proteins (RAMPs) 1, 2 and 3. CLR-RAMP signaling activated by adrenomedullin peptide is required for the development and normal function of lymphatic vessels in mice and humans, while activation by calcitonin gene related peptide (CGRP) represents a breakthrough pharmacological target for migraine treatment. However, the cellular and signaling effects of CLR-RAMPs in different lymphatic vascular beds, and under the regulation of female sex hormones, has yet to be elucidated. Our preliminary data converge these signaling paradigms into a promising molecular hypothesis on how RAMPs can allosterically modify CLR receptor signaling in vascular cells to trigger and sustain the female-predominance of chronic migraine. We plan to use sophisticated genetic mouse models coupled to in vitro pharmacological and cell biological assays to address the integrative roles of RAMPs in vascular cells during migraine. We anticipate that our findings will provide novel insights into the cell-specific and hormonally-responsive processes that govern vascular CGRP signaling during migraine and shed new light onto the pharmacological targets and actions of anti-CGRP therapies commonly prescribed to treat migraine.


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 = $2,676,945 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	The National Institute of Neurological Disorders and Stroke (NINDS) Helping to End Addiction Long-term® (HEAL) Initiative	000	1	8/19/2026	NEW	$2,676,945
														Subtotal = $2,676,945

Grand Total All Awards = $2,676,945

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Allostery of RAMP-CLR Signaling in Vascular Cells During Migraine

Award Number: R01HL176992

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/20/2026

PERIOD OF PERFORMANCE END DATE: 11/30/2030

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