# Single cell and tissue level functional genomic analysis of astrocyte-related mechanisms in tauopathy

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $205,524

## Abstract

ABSTRACT
Genetic evidence indicates that glia, including microglia and astrocytes, play causal roles in Alzheimer’s disease.
Therefore, detailed mechanistic understanding of causal glial factors has strong potential to lead to new
therapies. However, little is known about neuronal-glial interactions and how emerging pictures of glial
heterogeneity and changing states over time contribute to disease. This proposal aims to define astrocyte
subtypes and states present across the spectrum of disease pathology in human neurodegenerative tauopathies,
and identify key regulatory factors with which to experimentally manipulate these subtypes and states for
mechanistic study, via three specific aims. First, through analyzing a unique single nuclear sequencing dataset
to identify diverse astrocyte subtypes and states present across a spectrum of tau pathology and
neurodegeneration, and integrating these data with other whole tissue and single cell datasets to identify
reproducible findings and observe relationships to other cell types. Second, by identifying and validating key
molecular regulators of disease-associated astrocyte subtypes and states by combining bioinformatics
predictions with experimental testing in human iPSC models. Third, by assessing the functional relationship
between specific astrocytes subtypes and states and neurodegeneration in vivo using mouse models of
neurodegeneration. By including both human post-mortem data, experimental human in vitro systems, and
mouse in vivo systems, I will focus on robust and reproducible findings that are amenable to detailed functional
and mechanistic study. Ensuring the success of this project is a rich institutional environment and mentorship
team of world-class leaders in single-cell sequencing, basic astrocyte biology, functional genomics, and
experimental disease modeling. The training aspects of this proposal complement a strong background in
molecular biology and biochemistry with a solid foundation in genomics and bioinformatics as well as astroglial
biology. Altogether, the proposed work completes a professional transition to independent investigator focused
on glial mechanisms of neurodegeneration, by establishing the necessary experience and publication record in
the integration of functional genomics and single-nuclear sequencing with experimental glia biology.

## Key facts

- **NIH application ID:** 10242096
- **Project number:** 5K08NS105916-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jessica E Rexach
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,524
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242096

## Citation

> US National Institutes of Health, RePORTER application 10242096, Single cell and tissue level functional genomic analysis of astrocyte-related mechanisms in tauopathy (5K08NS105916-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242096. Licensed CC0.

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