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Investigating Pathogenic Mechanisms of Frontotemporal Dementia Caused by Mutations in CHMP2B and TBK1

Award Number: R37NS057553
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2018
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Investigating Pathogenic Mechanisms of Frontotemporal Dementia Caused by Mutations in CHMP2B and TBK1 - ABSTRACT Frontotemporal dementia (FTD) is a progressive neurodegenerative disease associated with focal atrophy of the prefrontal and/or temporal lobes. FTD is the second most common form of dementia among people under the age of 65. Many FTD-causing genes have been identified during the last decade, including CHMP2B, GRN, C9ORF72, and TBK1. Some of these genes are also implicated in the motor neuron disease amyotrophic lateral sclerosis (ALS), paving the way for in-depth mechanistic investigation of pathogenic processes in both disorders. In order to reveal common pathogenic mechanisms in different forms of FTD, it is critically important to investigate both common and rare genetic mutations. To this end, in this application, we will focus on the effects of FTD-causing mutations in CHMP2B and TBK1 on the functions of the endosomal- lysosomal and autophagy pathways, two closely linked cellular pathways for degradation of transmembrane and intracellular cargos. We will take advantage of strengths of different experimental systems including fruitfly Drosophila, mouse models of FTD and cortical neurons differentiated from CRISPR-engineered induced pluripotent stem cells (iPSCs). This multidisciplinary approach will greatly enhance our understanding of pathogenic mechanisms of FTD and reveal novel targets for therapeutic intervention.


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 = $634,466 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	11/23/2023	NON-COMPETING CONTINUATION	$588,679
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	4/10/2024	NON-COMPETING CONTINUATION	$45,787
														Subtotal = $634,466

Issue Date FY: 2023 ( Subtotal = $654,088 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	12/7/2022	NON-COMPETING CONTINUATION	$588,679
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	17	1/30/2023	NON-COMPETING CONTINUATION	$65,409
2023	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	11/21/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $654,088

Issue Date FY: 2022 ( Subtotal = $654,088 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	12/20/2021	EXTENSION WITH OR WITHOUT FUNDS	$588,679
2022	2022	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	3/24/2022	EXTENSION WITH OR WITHOUT FUNDS	$65,409
2022	2022	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	16	8/16/2022	EXTENSION WITH OR WITHOUT FUNDS	$326,530
2022	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	15	8/16/2022	NON-COMPETING CONTINUATION	-$326,530
														Subtotal = $654,088

Issue Date FY: 2021 ( Subtotal = $594,625 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	1/26/2021	NON-COMPETING CONTINUATION	$59,463
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	11/23/2020	NON-COMPETING CONTINUATION	$535,162
														Subtotal = $594,625

Issue Date FY: 2020 ( Subtotal = $594,625 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	11/21/2019	NON-COMPETING CONTINUATION	$535,162
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	2/12/2020	NON-COMPETING CONTINUATION	$59,463
														Subtotal = $594,625

Issue Date FY: 2019 ( Subtotal = $594,625 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	11/28/2018	NON-COMPETING CONTINUATION	$594,625
														Subtotal = $594,625

Issue Date FY: 2018 ( Subtotal = $594,625 )
2018	2018	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	12/22/2017	COMPETING CONTINUATION	$594,625
														Subtotal = $594,625

Grand Total All Awards = $4,321,142

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Investigating Pathogenic Mechanisms of Frontotemporal Dementia Caused by Mutations in CHMP2B and TBK1

Award Number: R37NS057553

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2018

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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