Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Roles for histone monoaminylation in cocaine-induced transcriptional and behavioral plasticity

Award Number: DP1DA042078
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2022

Group Awards By:

View Award Description

Roles for histone monoaminylation in cocaine-induced transcriptional and behavioral plasticity - Project Summary: Maze, IS, Ph.D. Persistent changes in neuronal gene expression promote physiological alterations implicated in a wide variety of human neurodevelopmental and adult psychiatric disorders. More recently, cell-type and brain region specific `epigenetic' mechanisms have been demonstrated to regulate transcriptional programs contributing to addiction-like behaviors; however, our understanding of how these mechanisms mediate life-long addiction remains limited. Monoaminergic neurotransmission in the central nervous system plays a critical role in psychostimulant-induced neural plasticity, with alterations in monoamine production/function being implicated in both the development and treatment of substance abuse disorders. Although packaging of monoamines by the vesicular monoamine transporter is essential for numerous aspects of reward, recent data have demonstrated the additional presence of `reserve' pools of extravesicular monoamines in the nucleus of monoamine producing neurons. Dopamine, as well as other monoamines, has previously been shown to form covalent bonds with certain cytoplasmic proteins catalyzed by the tissue Transglutaminase 2 enzyme. We recently identified histone proteins – histones are highly abundant, post-translationally modified proteins, which constitute the building blocks of eukaryotic chromatin and form the fundamental repeating units of transcription in mammalian cells – as robust substrates for monoaminylation in brain. Our data indicate that histone H3 dopaminylation likely acts to potentiate binding of adjacent histone posttranslational modification (PTM) interacting proteins (`readers') and may play a direct and critical role in dopaminergic neuronal transcription. Furthermore, our data demonstrate that chronic withdrawal from volitional administration of extended access to cocaine in rodents results in high levels of dopamine accumulation in the nucleus of dopamine producing neurons in the ventral tegmental area (an important structure within the mesolimbic reward circuitry), as well as increased cytoplasmic to nuclear shuttling of TGM2, the H3 dopaminylase. Take together, these data suggest that persistent states of addiction may result from increased genomic enrichment of H3 dopaminylation, potentiation of aberrant transcriptional plasticity and increased drug seeking behaviors. Using a unique combination of chromatin biochemistry, chemical biology, genome-wide and functional neurobiological approaches, we plan to fully characterize the functions of histone dopaminylation, both in the context of normal neuronal function and in ethologically valid rodent models of drug abuse; understanding these highly novel molecular phenomena promises to provide new insights into the underlying mechanisms of drug addiction, and aims to identify novel targets for the development of more effective therapeutics. Lastly, given the fundamental role other monoaminergic systems (e.g., serotonin, norepinephrine) in addiction, we believe that this `paradigm shifting' work will serve as a launching pad for countless future investigations aimed at fully delineating the `epigenetic' mechanisms at play in the development of substance abuse disorders.


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: 2023 ( Subtotal = $0 )
2023	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	6	5/3/2023	NON-COMPETING CONTINUATION	$0
2023	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	001	6	5/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $508,500 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	6	4/16/2021	NON-COMPETING CONTINUATION	$508,500
														Subtotal = $508,500

Issue Date FY: 2020 ( Subtotal = $508,500 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	5	4/22/2020	NON-COMPETING CONTINUATION	$508,500
														Subtotal = $508,500

Issue Date FY: 2019 ( Subtotal = $635,625 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	4	4/15/2019	NON-COMPETING CONTINUATION	$508,500
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	002	4	7/10/2019	NON-COMPETING CONTINUATION	$0
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	001	4	6/21/2019	SUPPLEMENT FOR EXPANSION	$127,125
														Subtotal = $635,625

Issue Date FY: 2018 ( Subtotal = $508,500 )
2018	2018	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	3	4/23/2018	NON-COMPETING CONTINUATION	$508,500
														Subtotal = $508,500

Issue Date FY: 2017 ( Subtotal = $508,500 )
2017	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	000	2	4/17/2017	NON-COMPETING CONTINUATION	$457,650
2017	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Drug Use and Addiction Research Programs	001	2	5/22/2017	NON-COMPETING CONTINUATION	$50,850
														Subtotal = $508,500

Issue Date FY: 2016 ( Subtotal = $508,500 )
2016	2016	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL, BOX 3500	NEW YORK-NEW YORK	NY	10029		USA	Drug Use and Addiction Research Programs	000	1	5/31/2016	NEW	$508,500
														Subtotal = $508,500

Grand Total All Awards = $3,178,125

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Roles for histone monoaminylation in cocaine-induced transcriptional and behavioral plasticity

Award Number: DP1DA042078

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer