Dissertations and Theses (Open Access)

Author ORCID Identifier

0000-0002-5409-9232

Date of Graduation

8-2026

Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Jian Hu

Committee Member

Daniel Frigo

Committee Member

Hyun Kyoung Lee

Committee Member

David Grosshans

Committee Member

Hyun Ei Kim

Committee Member

Vihang A, Narkar

Abstract

Astrocytes are the predominant glial cell type in the central nervous system (CNS) and are essential for maintaining its homeostasis through regulation of neurotransmitter clearance, metabolic support, blood-brain barrier integrity, and ion and water equilibrium. While the importance of these homeostatic functions is well established, the molecular regulators that coordinate astrocyte homeostasis are still not fully understood. The RNA-binding protein Quaking (QKI) has emerged as an important regulator of glial biology; more recently it’s been implicated in astrocyte biology. However, whether astrocytic QKI coordinates the molecular programs required to maintain CNS homeostasis and neurological function remain unclear. To further investigate this, we generated an inducible astrocyte-specific Qki knockout mouse model.

Astrocyte-specific deletion of Qki resulted in progressive severe neurological dysfunction and histological abnormalities within the CNS. Transcriptomic profiling identified coordinated dysregulation of genes involved in lipid metabolism, glutamate and amino acid transport and astrocyte-associated homeostatic functions. These transcriptional programs are required for normal astrocyte physiology, and its disruption under QKI loss induces neurological dysfunction and cellular abnormalities. Together, these findings highlight QKI as a critical regulator of astrocyte function and CNS integrity

Keywords

QKI, astrocytes, CNS homeostasis, oligodendrocytes

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Available for download on Friday, August 13, 2027

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