3 week old forebrain organoids
Research Overview
The Pak Lab is broadly interested in understanding how the human brain develops and functions from early embryonic stages through adulthood, and how disruptions in these processes contribute to neurodevelopmental and neuropsychiatric disorders. We focus on synapse development—a critical period when neurons and astrocytes form active, polarized connections that enable fast and efficient communication across neural circuits. Extensive human genetic studies have shown that synaptic dysfunction is a core feature of both neurodevelopmental and neurodegenerative brain disorders.
To address these questions, we aim not only to uncover the fundamental biology of synapse formation, specification, and maintenance in health and disease, but also to advance new cellular and molecular tools that allow us to investigate these processes in human-relevant systems. Our lab utilizes human pluripotent stem cell-derived neural models—including induced neurons (iNs) and brain organoids—to study human synaptic biology and disease mechanisms.
Our current projects center on three major research areas:
Synaptic dysfunction in complex brain disorders
Developmental deficits associated with neurodevelopmental syndromes
Development of improved human iPSC-based tools
We take an integrative approach combining CRISPR/Cas9 gene editing, patient-derived iPSCs, biochemistry, single-cell transcriptomics, proteomics, and electrophysiology. Our work is enriched through collaborations with experts in neurobiology, human genetics, biochemistry, and engineering, as well as with physicians who care for individuals with neurodevelopmental disorders.