Saturday, November 23, 2024 11/23/2024

Development and Application of Nicotinic Acetylcholine Receptor Targeted Peptides for Biomedical Research

Award Number: R35GM136430
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Nicotinic acetylcholine receptors (nAChRs) are broadly expressed in the CNS where they modulate the release of key neurotransmitters involved in learning, mood, and reward. nAChRs are also found in diverse non- neuronal tissues including immune cells, skin, gastro-intestinal epithelium and breast tumors. Research in our laboratory, which has been funded by R01 GM103801 and a project of P01 GM48677, is focused on enabling mechanistic understanding of how nAChRs regulate signaling at the single cell and systems levels. Venoms from predatory marine snails, known as Conus, are the richest known source of diverse, evolutionarily-refined ligands that target nAChRs. We have made substantial progress in developing peptides from these venoms that are selective for α6 subunit-containing subtypes of nAChRs. These peptides have been widely used to demonstrate that specific nAChR subtypes modulate key dopaminergic circuits that are strongly implicated in the addictive properties of drugs and in movement disorders such as Parkinson’s disease. Separately, we made groundbreaking progress in validating the α9α10 nAChR as a novel target for treatment of neuropathic pain. We enabled such progress by developing potent and highly selective conopeptides. Over the next 5 years, an overarching goal of our research program will be to develop robust suites of potent, highly selective conopeptide-based probes for the study of additional subtypes of nAChRs. We will continue to exploit the resulting compounds for applications in medicine. A particular focus will be to develop new ligands with high specificity for nAChR subtypes of non-neuronal cells. The most widely expressed nAChRs in non-neuronal cells have α7, α9, α10 and α5 subunits where our insight into function is limited. We will utilize the resulting peptide probes to examine the structures and functions of these nAChR subtypes. We have demonstrated that block of α9α10 nAChRs is analgesic in multiple animal models of neuropathic pain. Of high interest to us, is that selective conopeptides not only alleviate neuropathic pain, but they also prevent development of, or accelerate recovery from, nerve injury. Thus, the underlying therapeutic mechanism has significant implications for truly disease-modifying therapies. We will test the hypothesis that modulation of nAChRs in non-neuronal cells is key to understanding disease modification observed in models of trauma-, chemotherapy- and diabetes-induced nerve injury.


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 = $0 )
2025	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	5	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $449,875 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	5	1/5/2024	NON-COMPETING CONTINUATION	$404,889
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	5	8/6/2024	NON-COMPETING CONTINUATION	$44,986
														Subtotal = $449,875

Issue Date FY: 2023 ( Subtotal = $449,875 )
2023	2023	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	4	1/18/2023	NON-COMPETING CONTINUATION	$404,889
2023	2023	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	4	4/5/2023	NON-COMPETING CONTINUATION	$44,986
														Subtotal = $449,875

Issue Date FY: 2022 ( Subtotal = $449,875 )
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	3	6/22/2022	NON-COMPETING CONTINUATION	$44,986
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	3	1/13/2022	NON-COMPETING CONTINUATION	$404,889
														Subtotal = $449,875

Issue Date FY: 2021 ( Subtotal = $449,875 )
2021	2021	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	2	1/29/2021	NON-COMPETING CONTINUATION	$404,888
2021	2021	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	2	2/12/2021	NON-COMPETING CONTINUATION	$44,987
														Subtotal = $449,875

Issue Date FY: 2020 ( Subtotal = $493,474 )
2020	2020	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	001	1	6/2/2020	SUPPLEMENT FOR EXPANSION	$43,599
2020	2020	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Biomedical Research and Research Training	000	1	3/11/2020	NEW	$449,875
														Subtotal = $493,474

Grand Total All Awards = $2,292,974

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Development and Application of Nicotinic Acetylcholine Receptor Targeted Peptides for Biomedical Research

Award Number: R35GM136430

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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