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Investigating the Role and Heterogeneity of Reactive Astrocytes in Toxoplasma-Induced Brain Inflammation

Award Number: F32AI197530
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2026
PERIOD OF PERFORMANCE END DATE: 09/29/2027

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Investigating the Role and Heterogeneity of Reactive Astrocytes in Toxoplasma-Induced Brain Inflammation - Project Summary The common protozoan parasite Toxoplasma gondii is estimated to infect up to a third of the human population and forms a lifelong infection within the brain. While typically asymptomatic, individuals with compromised immune systems are at an increased risk for severe disease and death. Astrocytes are known to regulate both T. gondii replication and immune responses in the brain. In the healthy brain, astrocytes normally help regulate homeostasis by participating in the maintenance of the blood brain barrier, facilitating transport of nutrients and waste, providing synaptic support, and responding to immune insults. In response to central nervous system (CNS) insult, astrocytes undergo morphological, transcriptional, and functional changes to transition into what are known as reactive astrocytes (RAs). RA responses can vary across disease state, location in the brain, and proximity to the insult. Whether protective or detrimental to recovery, the precise role of RAs in neuroinflammation remains poorly understood. Two key challenges in studying RAs are their heterogeneity and the lack of tools to selectively target these cells. Our group has previously established a novel mouse line that utilizes Lipocalin 2 (Lcn2) as a driver for tamoxifen-dependent Cre, Lcn2-CreERT2, that selectively labels a subset of reactive astrocytes. We have identified an additional marker that is upregulated over 17-fold in astrocytes following LPS-induced inflammation. Astrocytes are the primary source of this marker in the central nervous system. Using this knowledge, we have created a new mouse line which uses the endogenous promoter for this marker to drive expression of a tamoxifen-dependent FlpO recombinase in subsets of reactive astrocytes. I will use this line to label and manipulate specific subsets of reactive astrocytes, determine their gene and protein expression, and track them over the course of infection. This newly created line and the Lcn2-CreERT2 line will be used to further investigate the heterogeneity of RAs and determine the functional roles of these RAs during T. gondii infection. Aim 1 will define the molecular and spatial characteristics of the marker+ reactive astrocytes by using the NanoString GeoMx platform to reveal the spatial proteomic and transcriptomic changes associated with neuroinflammation caused by T. gondii. Aim 2 will determine the functional phenotypes of these marker+ astrocyte subpopulations during T. gondii infection using FACS to isolate these RAs and examine their capabilities in primary culture. This work will provide critical insights into the development, function, and resolution of RA subsets during chronic infection and improve our understanding of astrocyte heterogeneity and their responses to neuroinflammation.


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: 2026 ( Subtotal = $76,300 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	000	1	3/30/2026	NEW	$75,052
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Allergy and Infectious Diseases Research	001	1	4/13/2026	NEW	$1,248
														Subtotal = $76,300

Grand Total All Awards = $76,300

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Investigating the Role and Heterogeneity of Reactive Astrocytes in Toxoplasma-Induced Brain Inflammation

Award Number: F32AI197530

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2026

PERIOD OF PERFORMANCE END DATE: 09/29/2027

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