Dilek Colak

Emerging data implicates a role for astrocyte dysfunction in neurodevelopmental and neuropsychiatric diseases. To study astrocyte pathology in ASD and Schizophrenia (SCZ), we combine patient iPSC-derived in vitro models with cell transplantation techniques to generate humanized mouse models. This enables us to assess synaptic plasticity and behavioral outcomes derived from ASD or SCZ astrocytes. Similarly, we also use organoids to 1) study early developmental deficits in neuropsychiatric diseases and 2) determine signatures of narcotic and neuropsychiatric risk factors in developing human cortices. In our most recent study, we strategically combined stem cell culturing with transplantation techniques to determine disease specific properties inherent to ASD derived astrocytes. We demonstrate that ASD astrocytes induce repetitive behavior as well as impair memory and long-term potentiation when transplanted into the healthy mouse brain. These in vivo phenotypes were accompanied by reduced neuronal network activity and spine density caused by ASD astrocytes in hippocampal neurons in vitro. Transplanted ASD astrocytes also exhibit exaggerated Ca2+ fluctuations in chimeric brains. Another major focus of our research asks how mRNA regulation contributes to synaptic plasticity and cognition. Our recent work established that local protein synthesis is regulated at the level of mRNA degradation in dendrites. 

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Current Projects:

• Autism
• Astrocyte functions
• RNA regulation
• Electrophysiology, Behavior