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Investigating Dysregulation of Stress-related Ribonucleoprotein Granules and Functions of Associated RNA-binding Proteins in ALS/FTD

Award Number: R01NS110098
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Protein and RNA homeostasis are two major themes in the study of neurodegenerative diseases, as exemplified by the implications of many RNA-binding proteins (RBPs) in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative conditions. As a major pathology in ALS/FTD, protein misfolding and aggregation, including those initiated by RBPs, manifest as a common thread among many neurodegenerative diseases. Additionally, a large collection of genetic, biochemical, and pathological evidence underscores the importance of RBPs in ALS/FTD and other neurodegenerative disease and calls for a better understanding of the functions of these RBPs and their associated cellular processes. A prominent feature of RBPs is their involvement in the formation of ribonucleoprotein (RNP) granules, including stress granules that are formed by a variety of RNAs and proteins under stress conditions. Stress-induced RNP granules are considered to play important roles as part of normal stress responses in the cell and in the pathological cascades underlying a range of human diseases including neurodegeneration. However, the molecular basis of RNP granule formation and the full spectrum of RBP functions remain to be elucidated. The goal of the proposed project is to investigate the molecular mechanism of protein and RNA homeostasis related to stress-induced RNP granules and disease-associated RBPs. The specific aims include understanding the diversity and functions of stress-induced granules in physiological and disease-relevant conditions, elucidate the mechanism of context-dependent granule assembly, and uncover novel functions of disease- associated RBPs such as TIA1. We propose a series of fundamental studies that combine biochemical, molecular, and genetic approaches and usage of state-of-art cellular and animal models to shed light on the novel structures and pathways related to protein and RNA homeostasis and ALS/FTD pathogenesis. Successful completion of the project is expected to provide insights into fundamental mechanisms of neurodegeneration in ALS/FTD that may ultimately lead to development of novel interventions to treat ALS/FTD and other relevant neurodegenerative diseases.


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: 2025 ( Subtotal = $564,290 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	11/25/2024	NON-COMPETING CONTINUATION	$564,290
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	11/1/2024	COMPETING CONTINUATION	$118,936
2025	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/1/2024	NON-COMPETING CONTINUATION	-$118,936
														Subtotal = $564,290

Issue Date FY: 2024 ( Subtotal = $634,358 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/21/2023	COMPETING CONTINUATION	$634,358
														Subtotal = $634,358

Issue Date FY: 2023 ( Subtotal = $516,155 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/5/2022	NON-COMPETING CONTINUATION	$516,155
														Subtotal = $516,155

Issue Date FY: 2022 ( Subtotal = $527,280 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/19/2021	NON-COMPETING CONTINUATION	$474,552
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	3/24/2022	NON-COMPETING CONTINUATION	$52,728
														Subtotal = $527,280

Issue Date FY: 2021 ( Subtotal = $949,425 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	9/21/2021	SUPPLEMENT FOR EXPANSION	$417,888
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/14/2020	NON-COMPETING CONTINUATION	$478,383
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/18/2021	NON-COMPETING CONTINUATION	$53,154
														Subtotal = $949,425

Issue Date FY: 2020 ( Subtotal = $543,000 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/20/2019	NON-COMPETING CONTINUATION	$543,000
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	2/17/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $543,000

Issue Date FY: 2019 ( Subtotal = $543,000 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/18/2019	NEW	$543,000
														Subtotal = $543,000

Grand Total All Awards = $4,277,508

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Investigating Dysregulation of Stress-related Ribonucleoprotein Granules and Functions of Associated RNA-binding Proteins in ALS/FTD

Award Number: R01NS110098

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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