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Identification and characterization of a new pericyte subset: Role in blood-brain barrier breakdown

Award Number: F31NS116926
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Project Summary/Abstract Blood-brain barrier (BBB) breakdown is commonly noted in association with numerous neurocognitive disorders and can exacerbate persistent neurological issues by allowing the leakage of toxic and pathogenic materials into the brain. While this disruption is often associated with neuroinflammation which therapeutically difficult to target, our recent research in rhesus macaques has led to the observation of morphologically abnormal pericytes in regions of BBB breakdown. These phenotypically distinct pericytes, named type 2 pericytes (PC2), have been shown to increase in number with age and infection status and are specifically associated with vessels demonstrating decreased tight junction protein levels and increased fibrinogen extravasation. Our studies indicate that PC2 may be a valuable therapeutic target to reduce BBB breakdown and maintain selective permeability. We hypothesize that BBB supportive type 1 pericytes (PC1) are becoming PC2 during BBB disruption and that PC2 have differential expression from PC1 in pathways known to regulate BBB homeostatic function. In this study, we propose to investigate the differentiation of PC2 by determining whether known BBB- disrupting factors can initiate a PC1-to-PC2 transition in vitro and in vivo. Additionally, we will analyze the transcriptomic and proteomic differences between PC1 and PC2 to determine differentially regulated pathways that may impact BBB health in the hopes of identifying potential therapeutic targets. The fulfilment of these aims will improve our understanding of how PC2 develop in vivo and why PC2 are less supportive of the BBB than PC1.


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 = -$3,805 )
2024	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/22/2024	NON-COMPETING CONTINUATION	-$3,805
														Subtotal = -$3,805

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $30,753 )
2022	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/9/2022	NON-COMPETING CONTINUATION	$30,753
														Subtotal = $30,753

Issue Date FY: 2021 ( Subtotal = $30,036 )
2021	2021	EASTERN VIRGINIA MEDICAL SCHOOL	358 MOWBRAY ARCH STE 305	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	7/29/2021	NON-COMPETING CONTINUATION	$30,036
2021	2020	EASTERN VIRGINIA MEDICAL SCHOOL	358 MOWBRAY ARCH STE 305	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	12/14/2020	NEW	$0
2021	2020	EASTERN VIRGINIA MEDICAL SCHOOL	358 MOWBRAY ARCH STE 305	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/10/2020	NEW	$0
														Subtotal = $30,036

Issue Date FY: 2020 ( Subtotal = $29,520 )
2020	2020	EASTERN VIRGINIA MEDICAL SCHOOL	358 MOWBRAY ARCH STE 305	NORFOLK	VA	23507	NORFOLK CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/18/2020	NEW	$29,520
														Subtotal = $29,520

Grand Total All Awards = $86,504

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Identification and characterization of a new pericyte subset: Role in blood-brain barrier breakdown

Award Number: F31NS116926

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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