# TAOK2 Kinase Signaling in Human Neural Stem Cell Development

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $442,496

## Abstract

Increasing evidence indicates that aberrations in neural stem cell proliferation and early neurogenesis
are critically involved in the pathogenesis of neurodevelopmental and psychiatric disorders. Despite being
implicated in pathophysiology of several neurological diseases, the mechanisms through which human kinome
controls neurogenesis and how its dysfunction manifests in disease remain major gaps in the field of
neurodevelopmental biology. In this proposal, we will investigate the role of an autism susceptibility gene,
TAOK2, which encodes a serine threonine kinase, in human neural stem cell development and function. Both
loss-of-function and activating TAOK2 mutations have been associated with autism spectrum disorders (ASD).
Further, TAOK2 is one of the genes in the 16p11.2 genomic locus, copy number variation (CNV) of which is
the most prevalent genetic risk factor associated with ASD. While work by us and others has demonstrated
compelling evidence that TAOK2 is important for neuronal and synaptic development, the role of TAOK2 in
human neural progenitor cell (NPC) development and differentiation has not been investigated. Further, the
contribution of TAOK2 in the pathology associated with 16p11.2 copy number variation is unknown. Based on
the strength of our preliminary findings, the central hypothesis of this research proposal is that TAOK2 kinase
orchestrates a signaling hub at the centrosome that regulates human neural progenitor stem cell development,
and that perturbation of this signaling pathway contributes to pathogenesis of ASD. We will elucidate the role of
TAOK2 in NPC development through use of 2D and 3D human induced pluripotent stem cell (hiPSC) models
(Aim1). Next, mechanisms through which TAOK2 regulates ciliary growth and signaling will be determined
using super-resolution imaging and biochemical approaches (Aim2). The contribution of TAOK2 in the ciliary
defects observed in patient-derived NPCs from 16p11.2 deletion and duplication carriers will be determined
through application of quantitative proteomics and genome editing techniques (Aim3). Utilizing a combination
of innovative approaches and human disease relevant model systems, we seek to understand how TAOK2
kinase signaling mediates neural stem cell development, and how perturbations in its signaling pathways
contribute to the clinical neuropathology of 16p11.2 CNV.
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## Key facts

- **NIH application ID:** 10737612
- **Project number:** 5R01MH121674-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Smita Yadav
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $442,496
- **Award type:** 5
- **Project period:** 2019-12-02 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10737612

## Citation

> US National Institutes of Health, RePORTER application 10737612, TAOK2 Kinase Signaling in Human Neural Stem Cell Development (5R01MH121674-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10737612. Licensed CC0.

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