Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Illuminating Reactive Astrocyte Contributions to Alzheimer’s Pathology via PIP-sort Technology

Award Number: R01AG100367
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2031

Group Awards By:

View Award Description

Illuminating Reactive Astrocyte Contributions to Alzheimer’s Pathology via PIP-sort Technology - PROJECT SUMMARY Astrocytes—supportive glial cells in the brain—undergo significant changes in Alzheimer’s disease (AD), becoming reactive and contributing to disease progression. These reactive astrocytes, characterized by markers such as SERPINA3, GFAP δ, and PLXNB1, are scarce in postmortem brain tissues, making them difficult to study with conventional methods. Traditional single-nucleus RNA sequencing requires analyzing vast numbers of cells to capture these rare populations, and standard fluorescence-activated cell sorting (FACS) techniques are ineffective on nuclei due to the absence of surface markers. To overcome these challenges, we introduce PIP-sort, an innovative, microfluidic-free method that enables the isolation and detailed analysis of rare astrocyte nuclei from frozen brain samples. PIP-sort utilizes droplet digital PCR (ddPCR) to amplify specific mRNA transcripts within droplets, causing them to fluoresce. This fluorescence allows for the rapid sorting of targeted nuclei using standard FACS equipment. Each nucleus is paired with a barcoded bead, facilitating the capture of its full-length cDNA and, with additional processing, its chromatin accessibility profile. This approach yields high- resolution, single-nucleus RNA and ATAC sequencing data, providing insights into both gene expression and epigenetic regulation. Our project comprises three specific aims: · Validation of PIP-sort: We will optimize and validate the PIP-sort technique using synthetic mixtures of human and mouse cells to demonstrate its capability in enriching rare cell types based on mRNA markers. · Multi-omic Profiling: We will extend PIP-sort to simultaneously profile transcriptomic and epigenomic landscapes of isolated nuclei, enabling a comprehensive understanding of the regulatory mechanisms in reactive astrocytes. · Functional Analysis: Applying PIP-sort to human AD brain samples, we will isolate reactive astrocyte populations and identify key regulatory genes. Subsequent CRISPR/Cas9-mediated perturbations in mouse models will assess the causal roles of these genes in amyloid and tau pathologies and cognitive decline. By facilitating the study of elusive astrocyte subpopulations directly from archival human tissues, PIP-sort aims to uncover novel therapeutic targets and advance our understanding of glial contributions to Alzheimer’s disease.


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 = $700,564 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Aging Research	000	1	9/17/2026	NEW	$700,564
														Subtotal = $700,564

Grand Total All Awards = $700,564

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Illuminating Reactive Astrocyte Contributions to Alzheimer’s Pathology via PIP-sort Technology

Award Number: R01AG100367

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer