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Molecular Mechanisms of Chromatin Remodeling Proteins in Alzheimers Disease

Award Number: R01DC015000
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2022

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Molecular Mechanisms of Chromatin Remodeling Proteins in Alzheimers Disease - ABSTRACT Sporadic Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss. Pathogenic β-amyloid (Aβ) plaques are a hallmark of AD, starting first in the hippocampus before spreading to other parts of the brain. Initial research has primarily focused on how Aβ aggregates are formed. Despite progress made in understanding progression of AD pathology, fundamental questions remain about what molecular determinants contribute to the onset of AD. Age-dependent genomic changes likely play a role in AD but the molecular players involved have yet to be defined. We show that Chd4, a nucleosome repositioning enzyme, dramatically decreases expression with age in pyramidal neurons of the hippocampus. We propose that Chd4 deletion mimics the epigenomic landscape of old neurons to accelerate the onset of AD pathology. The goal of the proposal is to address the function of Chd4 in the context of AD. We will use tools in single-cell transcriptomics and super-resolution microscopy to determine the molecular changes that occur in pyramidal neurons (Aim1) and the composition of synaptic proteins as well as the integrity of neuronal circuits in the hippocampus (Aim2) after deleting Chd4. We will also determine if Aβ plaques and memory loss are observed in animals lacking Chd4 (Aim3).


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 = -$151 )
2023	2020	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	001	5	6/8/2023	SUPPLEMENT FOR EXPANSION	-$82
2023	2020	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	5	5/15/2023	NON-COMPETING CONTINUATION	-$69
														Subtotal = -$151

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	001	5	8/24/2022	NON-COMPETING CONTINUATION	$0
2022	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	002	5	8/24/2022	SUPPLEMENT FOR EXPANSION	$151
2022	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	5	7/13/2022	SUPPLEMENT FOR EXPANSION	-$151
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $719,375 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	001	5	6/18/2020	SUPPLEMENT FOR EXPANSION	$390,000
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	5	4/14/2020	NON-COMPETING CONTINUATION	$329,375
														Subtotal = $719,375

Issue Date FY: 2019 ( Subtotal = $329,375 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	4	4/17/2019	NON-COMPETING CONTINUATION	$329,375
														Subtotal = $329,375

Issue Date FY: 2018 ( Subtotal = $329,375 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	3	4/27/2018	NON-COMPETING CONTINUATION	$329,375
														Subtotal = $329,375

Issue Date FY: 2017 ( Subtotal = $329,375 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	001	2	5/24/2017	NON-COMPETING CONTINUATION	$32,938
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	2	5/2/2017	NON-COMPETING CONTINUATION	$296,437
														Subtotal = $329,375

Issue Date FY: 2016 ( Subtotal = $328,993 )
2016	2016	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	1	5/7/2016	NEW	$328,993
														Subtotal = $328,993

Grand Total All Awards = $2,036,342

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Molecular Mechanisms of Chromatin Remodeling Proteins in Alzheimers Disease

Award Number: R01DC015000

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2022

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