# Molecular drivers of tauopathies in stem cell models from diverse human populations

> **NIH NIH K01** · WASHINGTON UNIVERSITY · 2024 · $126,981

## Abstract

Project Summary/Abstract
The overall goal of this research and training plan is to define the molecular mechanisms underlying
tauopathies in diverse populations. Currently, the contribution of specific MAPT mutations to tau toxicity, the
mechanisms by which tauopathies occur, and the contribution of different genetic backgrounds to these
mechanisms remain poorly understood. This project aims to define druggable molecular signatures of MAPT
mutations using stem cell models from African (Nigeria), Asian (Japan), and South American (Brazil)
populations.
The investigator, Dr. Miguel Minaya, will gain advanced training in stem cell biology and functional genomics in
support of an innovative approach that establishes novel cell models that use human induced pluripotent stem
cell (iPSC)-derived neurons, diverse populations, and CRISPR-based screens to study the extent to which
MAPT mutations occurring in diverse genetic backgrounds will produce common and/or unique molecular
signatures of disease. The mentors who were selected for this training, Drs. Celeste Karch, Carlos Cruchaga,
and Martin Kampmann, are internationally recognized experts in the fields of tau biology, human and molecular
genetics, stem cell biology, genome editing, and functional genomic screens using CRISPRi.
The goal of this proposal is to define druggable molecular signatures of MAPT mutations using stem cell
models from diverse populations. The overarching hypothesis of this proposal is that MAPT mutations
occurring in diverse genetic backgrounds will produce common molecular signatures of disease. To define
these common mechanisms, I will define molecular changes in iPSC-derived neurons from iPSC lines with
engineered MAPT mutations and will then functionally annotate those genes using CRISRPi screens. Through
this research and mentored training plan, Dr. Minaya will make fundamental contributions to our knowledge of
the mechanisms by which disruptions in the MAPT gene are associated with tauopathies and will establish new
experimental tools and approaches that will form the foundation for a career as an independent, translational
neuroscientist.

## Key facts

- **NIH application ID:** 10892256
- **Project number:** 5K01AG083215-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Miguel Minaya
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $126,981
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892256

## Citation

> US National Institutes of Health, RePORTER application 10892256, Molecular drivers of tauopathies in stem cell models from diverse human populations (5K01AG083215-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892256. Licensed CC0.

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