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Identifying Cell Type-Specific RNA Expression and Regulatory Changes in Entorhinal Cortex Clinical Samples of Alzheimer's Disease

Award Number: F31AG090056
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Identifying Cell Type-Specific RNA Expression and Regulatory Changes in Entorhinal Cortex Clinical Samples of Alzheimer's Disease - Spatial and temporal regulation of RNA is key to cellular homeostasis and can become disrupted in disease. The lifecycle of RNA can include splicing, modification, transport, and translation, which all require RNA-binding proteins (RBPs), a class of proteins that bind and regulate RNAs. Specifically in the brain, there are many neuronal and non-neuronal cell types that are each comprised of distinctive sets of transcripts with unique RNA regulatory machineries. While there are genetic tools in mice to parse out cell type-specific RNA regulation, a parallel tool does not currently exist to study this in human postmortem brain tissue, limiting the ability to study human diseases. We have developed crosslinking immunoprecipitation-Fluorescence Activated Nuclei Sorting (CLIP-FANS) which will allow us to overcome this hurdle and for the first time, identify cell-type specific RBP mediated RNA regulation in postmortem samples. CLIP-FANS builds on two previous methodologies: fluorescence-activated nuclei sorting (FANS) to achieve cell type specificity, followed by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) to analyze gene regulation in sorted populations. Here, we have built an ordered approach and show preliminary data of the similarities and differences in the Hu-binding between excitatory and inhibitory neurons in the human entorhinal cortex in the first iteration of CLIP-FANS. One neurodegenerative disorder with dysregulation of RNAs and RBPs in Alzheimer’s disease (AD), a highly prevalent disease and the leading cause of dementia. For therapeutic interventions, maximum benefit would be achieved by targeting the first brain regions affected in AD, such as the entorhinal cortex, which has few studies on gene expression changes and none on gene regulation changes. Therefore, a combined approach of RNA sequencing of sorted cell types (FANSseq) and CLIP-FANS will generate cell-type specific gene expression and regulatory data of the differences occurring in AD to identify potential 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: 2026 ( Subtotal = $50,114 )
2026	2026	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	2	8/26/2026	NON-COMPETING CONTINUATION	$50,114
														Subtotal = $50,114

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	001	1	8/21/2025	NEW	$0
2025	2025	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	1	8/21/2025	NEW	$49,538
														Subtotal = $49,538

Grand Total All Awards = $99,652

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Identifying Cell Type-Specific RNA Expression and Regulatory Changes in Entorhinal Cortex Clinical Samples of Alzheimer's Disease

Award Number: F31AG090056

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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