4 week old NGN2-induced neurons decorated with synaptic puncta 
Neural progenitors (SOX2+ MIK67+) in
3 week old forebrain organoids.
The overarching scientific interest of the Pak lab is to understand the molecular and cellular basis of how our brains develop and function from early embryonic stages through adulthood and to investigate how disruptions in these pathways contribute to neurodevelopmental/neuropsychiatric disorders. Specifically, we are interested in pursuing this big task by focusing on synapse development, a developmental period when neurons (and astrocytes) make active connections with one another. Synapses are polarized cellular junctions that organize fast and efficient signaling and communication between nerve cells. We now know from multiple human genetic studies that brain disorders (both neurodevelopmental and neurodegenerative disorders) arise from synaptic dysfunction.
To achieve this mission, we not only have to figure out the underlying biology of synapse formation, specification, and maintenance in healthy and disease states, but we must also develop novel cellular and molecular tools to approach these questions from human cellular contexts. In our lab, we utilize human pluripotent stem cell-derived neural models (i.e. induced neurons and brain organoids) to probe human synaptic biology and disease mechanisms.
Currently, in the lab, we are focusing on three major research areas:
Signaling mechanisms in neurodevelopment
Functional analysis of pathogenic variants in neuropsychiatric disorders
Development of improved human iPSC-based tools
We use a combination of approaches from gene editing, patient-derived iPSCs, biochemistry, omics, and electrophysiology and collaborate with experts in biochemistry, neurobiology, human genetics, and engineering to approach these questions from diverse scientific perspectives.