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Origins, properties, and therapeutic potential of cells that repopulate the microglia-depleted adult brain

Award Number: R01NS083801
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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Origins, properties, and therapeutic potential of cells that repopulate the microglia-depleted adult brain - Abstract: Our research focuses on microglia, a type of brain cell crucial to understanding and treating several central nervous system diseases. In our first funding cycle (2014-2019), we developed a technique to remove and replace microglia using a drug that targets a specific receptor (CSF1R), which has since become a standard method in neuroscience. This approach has significantly advanced our understanding of microglia and has shown therapeutic potential in various disease and injury models. In our second funding cycle (2019-2024), we further explored microglia replacement and discovered several key findings, including a new method of reprogramming microglia and a novel route for bone marrow-derived cells to enter the brain allowing us to fully replace the microglial tissue with bone-marrow derived monocytes/myeloid cells. Building on these findings, we propose three specific aims for our next research phase. First, we will investigate a new method of microglia recovery that avoids the need for complete microglia removal. This involves temporarily inhibiting CSF1R, leading to the reprogramming and proliferation of microglia and other brain cells. Second, we will explore the potential of replacing dysfunctional microglia with functional bone marrow-derived cells as a treatment for genetic disorders associated with microglia dysfunction. Lastly, we will study the role of peripheral myeloid cells entering the brain in the development of Alzheimer's disease. Our research aims to deepen our understanding of microglia biology and explore its therapeutic potential, moving towards more clinically relevant applications.


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 = $0 )
2025	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	1/22/2025	COMPETING CONTINUATION	$5,892
2025	2023	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/22/2025	NON-COMPETING CONTINUATION	-$5,892
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $715,019 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	9/19/2024	COMPETING CONTINUATION	$715,019
2024	2023	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	9/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $715,019

Issue Date FY: 2023 ( Subtotal = $373,512 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/30/2023	NON-COMPETING CONTINUATION	$373,512
														Subtotal = $373,512

Issue Date FY: 2022 ( Subtotal = $373,512 )
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	3/28/2022	NON-COMPETING CONTINUATION	$37,352
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/24/2022	NON-COMPETING CONTINUATION	$336,160
														Subtotal = $373,512

Issue Date FY: 2021 ( Subtotal = $373,512 )
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	1/27/2021	NON-COMPETING CONTINUATION	$373,512
														Subtotal = $373,512

Issue Date FY: 2020 ( Subtotal = $373,512 )
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/21/2020	NON-COMPETING CONTINUATION	$373,512
														Subtotal = $373,512

Issue Date FY: 2019 ( Subtotal = $373,512 )
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	1/25/2019	COMPETING CONTINUATION	$373,512
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	6/7/2019	COMPETING CONTINUATION	$70,594
2019	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/7/2019	NON-COMPETING CONTINUATION	-$70,594
														Subtotal = $373,512

Issue Date FY: 2018 ( Subtotal = $318,761 )
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	4/25/2018	NON-COMPETING CONTINUATION	$31,877
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/18/2018	NON-COMPETING CONTINUATION	$286,884
														Subtotal = $318,761

Issue Date FY: 2017 ( Subtotal = $319,848 )
2017	2017	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/16/2017	NON-COMPETING CONTINUATION	$287,863
2017	2017	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/13/2017	NON-COMPETING CONTINUATION	$31,985
														Subtotal = $319,848

Issue Date FY: 2016 ( Subtotal = $320,874 )
2016	2016	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/3/2016	NON-COMPETING CONTINUATION	$32,088
2016	2016	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/12/2016	NON-COMPETING CONTINUATION	$288,786
														Subtotal = $320,874

Issue Date FY: 2015 ( Subtotal = $321,841 )
2015	2015	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/9/2015	NON-COMPETING CONTINUATION	$321,841
														Subtotal = $321,841

Issue Date FY: 2014 ( Subtotal = $322,515 )
2014	2014	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/10/2014	NEW	$322,515
														Subtotal = $322,515

Grand Total All Awards = $4,186,418

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Origins, properties, and therapeutic potential of cells that repopulate the microglia-depleted adult brain

Award Number: R01NS083801

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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