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Combinatorial Perturbation with Multi-Omics Readout to Dissect Etiology of Alzheimer's Disease Using Stem Cell and In Vivo Models

Award Number: R01AG091819
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2025
PERIOD OF PERFORMANCE END DATE: 01/31/2030

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Combinatorial Perturbation with Multi-Omics Readout to Dissect Etiology of Alzheimer's Disease Using Stem Cell and In Vivo Models - Combinatorial Perturbation with Multi-Omics Readout to Dissect Etiology of Alzheimer's Disease Using Stem Cell and In Vivo Models Abstract Alzheimer's disease (AD) is a prevalent age-related neurodegenerative disorder. While early-onset AD is driven by well-characterized genes, the mechanistic links between aging and late-onset AD remain elusive. Human genetic studies have revealed numerous risk alleles that modulate AD susceptibility, but their complex interactions are challenging to study using current tools. We propose to develop Combo-Seq/Tag, a powerful toolkit combining precisely installing multiple risk alleles (Combo-Seq) with a multiplex protein tagging tool (Combo-Tag) for studying endogenous protein interactions. These tools will enable efficient perturbation of AD risk genes and multi-omics readouts in human stem cell models. We will also generate a Combo-Seq/Tag mouse strain compatible with the 5xFAD AD model for in vivo study. Our project will yield innovative products, including multiplex, optimized gene-editing vectors, and rich multi-omics datasets, amplifying the impact of AD human genetics studies. By providing a toolkit to dissect the complex genetic interactions underlying AD pathogenesis, our work will contribute to understanding the mechanistic links between aging and neurodegeneration, potentially revealing novel targets for AD diagnosis and therapy.


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 = $556,820 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	2	1/23/2026	NON-COMPETING CONTINUATION	$556,820
														Subtotal = $556,820

Issue Date FY: 2025 ( Subtotal = $619,681 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	1	3/13/2025	NEW	$619,681
														Subtotal = $619,681

Grand Total All Awards = $1,176,501

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Combinatorial Perturbation with Multi-Omics Readout to Dissect Etiology of Alzheimer's Disease Using Stem Cell and In Vivo Models

Award Number: R01AG091819

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/15/2025

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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