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Role of Dynamic Signaling of NRG3-ErbB4 in the Prefrontal Cortex in Mediating Nicotine Withdrawal Phenotypes

Award Number: F31DA057812
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/12/2024
PERIOD OF PERFORMANCE END DATE: 12/20/2025
AWARD TERMINATION DATE: 03/04/2026

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Role of Dynamic Signaling of NRG3-ErbB4 in the Prefrontal Cortex in Mediating Nicotine Withdrawal Phenotypes - PROJECT SUMMARY/ABSTRACT While several pharmacotherapies are currently available for nicotine dependence, smoking cessation is only 7.5% successful. Recent advances in the study of genetic contributions to nicotine dependence represent a promising avenue for the development of novel smoking cessation therapies. Our lab has shown that variations in the gene for Neuregulin 3 (NRG3) and its cognate receptor ErbB4 are linked to smoking cessation outcomes and may be responsible, in part, for affective nicotine withdrawal (WD) phenotypes. Therefore, the overarching goal of this fellowship-training proposal is to systematically investigate the region-specific, functional role of the Neuregulin Signaling Pathway during nicotine use and WD. To accomplish this, we are evaluating two central aims: 1) Determine the PFC-specific contributions of ErbB4 to nicotine WD related behavioral phenotypes and the mechanism by which they occur, and 2) Characterize expression patterns of NRG3-ErbB4 signaling within the prefrontal cortex and identify the molecular alterations induced during chronic nicotine and WD. Our approach is significant because it utilizes a novel genetic mouse model of nicotine dependence in a multidimensional approach to provide insight into the underlying mechanisms that define the NRG3 signaling pathway and its role in nicotine dependence. Research undertaken in this fellowship will be performed at the University of Kentucky College of Pharmacy under the purview of the Graduate Program in Pharmaceutical Sciences, a multidisciplinary program designed to prepare motivated individuals for academic, industrial, or government careers in pharmaceutical and biomedical research. My mentor, Dr. Jill Turner, has helped develop a training plan for my graduate career that consists of professional development and didactic training in techniques that will develop my understanding and expertise in the field. The outlined training plan will help me to develop expertise in the field of neuropharmacology/genetics of addiction, expand upon my experimental techniques, refine my experimental design and data analysis skills, and continue to work on my presentation and networking skills. The training gained during my graduate career under the guidance of Dr. Turner will provide me with a broad exposure to the neurobiology of substance use disorders; in addition to my research work, these experiences will help me in my future goals of developing novel precision therapeutics for nicotine dependence and other co-morbid psychiatric disorders. The combination of my dedicated mentor that will assist in the development and progression of my training with innovative research venues to conduct and share my research will warrant my success as a well-trained graduate student.


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: 2027 ( Subtotal = -$30,903 )
2027	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Drug Use and Addiction Research Programs	000	2	10/27/2026	NON-COMPETING CONTINUATION	-$30,903
														Subtotal = -$30,903

Issue Date FY: 2026 ( Subtotal = -$1,679 )
2026	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Drug Use and Addiction Research Programs	000	2	3/4/2026	TERMINATION	-$1,679
														Subtotal = -$1,679

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Drug Use and Addiction Research Programs	000	2	12/13/2024	NON-COMPETING CONTINUATION	$48,974
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Drug Use and Addiction Research Programs	001	2	8/15/2025	NON-COMPETING CONTINUATION	$564
														Subtotal = $49,538

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Drug Use and Addiction Research Programs	001	1	4/30/2024	NEW	$1,280
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Drug Use and Addiction Research Programs	000	1	12/27/2023	NEW	$47,694
														Subtotal = $48,974

Grand Total All Awards = $65,930

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Role of Dynamic Signaling of NRG3-ErbB4 in the Prefrontal Cortex in Mediating Nicotine Withdrawal Phenotypes

Award Number: F31DA057812

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/12/2024

PERIOD OF PERFORMANCE END DATE: 12/20/2025

AWARD TERMINATION DATE: 03/04/2026

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