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Gene Expression Programs in Maturing Dopamine Neurons: Temporal Regulation, Subcellular Localization, and Alteration by Amphetamine

Award Number: F30DA047775
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/15/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Gene Expression Programs in Maturing Dopamine Neurons: Temporal Regulation, Subcellular Localization, and Alteration by Amphetamine - Early initiation of drug use is associated with long-term poor social outcomes and higher rates of substance use disorders in adulthood. Altered dopamine (DA) neurotransmission in forebrain circuits is a hallmark of drug addiction and DA inputs to these circuits continue to mature into adolescence. Recent evidence suggests that adolescent drug exposure alters DA axonal maturation and disrupts proper forebrain development, resulting in persistent behavioral alterations that may increase the risk of drug addiction. In order to prevent long-term adverse outcomes related to adolescent drug use, we must understand the mechanisms by which drugs of abuse alter normal development of DA neurons. Postnatal development of DA neurons is complex: a small number of DA neurons must survive two rounds of cell death and mature their axonal innervation in expansive forebrain structures, suggesting tight regulation of developmental gene expression programs. These DA neuron developmental programs may be particularly susceptible to amphetamine, a psychostimulant drug of abuse that causes lasting changes in forebrain DA innervation when administered during early adolescence. This proposal will develop a precise understanding of gene expression in DA neurons across postnatal development and will analyze how early adolescent amphetamine exposure alters normal gene expression patterns. A combination of neuroanatomical, biochemical, next-generation sequencing, and systems biology approaches will be applied to a transgenic mouse that enables DA neuron-specific, genome-wide analysis of translating mRNAs. Aim 1 will identify changes in gene expression associated with 1) key transitional timepoints related to axonal growth and cell death in early postnatal development and 2) response to adolescent amphetamine exposure and prolonged axonal maturation during later postnatal development. Cell type-specific expression data will be used to elucidate and validate master regulator genes controlling DA neuron maturation. Aim 2 will explore the role of subcellular mRNA localization and protein synthesis in maturing DA neurons across the same conditions studied in Aim 1 (i.e., across postnatal development and following amphetamine exposure). The proposed research will enhance our understanding of DA neuronal cell biology and will have far reaching implications for the neurodevelopmental origins of drug addiction. This pre- doctoral fellowship will support rigorous scientific training of the applicant at Columbia University Medical Center. An interdisciplinary mentorship team with unique expertise will provide training in both neuroscience and systems biology, enhancing the applicant’s technical skills and professional development. The applicant will also undergo extensive clinical training, refining general clinical skills and providing field-specific exposure relevant to the applicant’s interest in neuropsychiatry. The activities proposed under this award will provide the applicant with the skills required to develop a successful career as an independent physician-scientist.


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 = -$10,500 )
2024	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	000	5	4/24/2024	NON-COMPETING CONTINUATION	-$10,500
														Subtotal = -$10,500

Issue Date FY: 2023 ( Subtotal = $35,716 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	001	5	2/7/2023	NON-COMPETING CONTINUATION	$471
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	002	5	7/21/2023	NON-COMPETING CONTINUATION	-$1,131
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	000	5	1/6/2023	NON-COMPETING CONTINUATION	$36,376
														Subtotal = $35,716

Issue Date FY: 2022 ( Subtotal = $51,752 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	002	4	5/20/2022	NON-COMPETING CONTINUATION	-$1
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	000	4	11/26/2021	NON-COMPETING CONTINUATION	$51,036
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	001	4	4/25/2022	NON-COMPETING CONTINUATION	$717
														Subtotal = $51,752

Issue Date FY: 2021 ( Subtotal = $51,036 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	001	3	2/4/2021	NON-COMPETING CONTINUATION	$516
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	000	3	12/1/2020	NON-COMPETING CONTINUATION	$50,520
														Subtotal = $51,036

Issue Date FY: 2020 ( Subtotal = $50,520 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	001	2	2/13/2020	NON-COMPETING CONTINUATION	$504
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	000	2	1/14/2020	NON-COMPETING CONTINUATION	$50,016
														Subtotal = $50,520

Issue Date FY: 2019 ( Subtotal = $50,016 )
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	001	1	12/19/2018	NEW	$0
2019	2019	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Drug Use and Addiction Research Programs	000	1	12/19/2018	NEW	$50,016
														Subtotal = $50,016

Grand Total All Awards = $228,540

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Gene Expression Programs in Maturing Dopamine Neurons: Temporal Regulation, Subcellular Localization, and Alteration by Amphetamine

Award Number: F30DA047775

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/15/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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