Understanding how identity programs shape brain development and dysfunction

We study how neurons acquire their identity, how that identity shapes cortical circuit formation, and how its disruption contributes to neurodevelopmental disease. We view neuronal identity as a dynamic and plastic developmental program shaped by both genetic instructions and environmental context.

Our lab combines brain organoid systems, machine learning, and electrophysiology to uncover how neuronal subtypes emerge, integrate, and function within developing circuits. We focus on building scalable experimental models that allow direct testing of how identity and environment interact to guide brain development.

We developed novel grafting protocols to generate chimeric organoid models, which allowed us to demonstrate that specific three-dimensional environments are sufficient to drive the specification of parvalbumin interneurons. Building on this, we established mouse cortical organoid models that endogenously produce parvalbumin interneurons, offering a new platform for studying inhibitory circuit assembly using the same embryonic stem cell lines as in vivo models.

We have also shown that postmitotic cortical neurons, including both excitatory projection neurons and interneurons, can reprogram their class-specific identity. This work reveals unexpected plasticity in neuronal fate and offers new tools for engineering neuronal diversity.

To support these efforts, we developed SIMS, a deep learning tool for cell type classification in single-cell transcriptomics, and HIPPIE, a model for identifying neuronal identity from electrophysiological recordings. These tools help bridge molecular identity with network-level function.

Our long-term goal is to build predictive and programmable frameworks that explain how identity programs guide brain development and how their disruption leads to disease. We are based at the UCSC Genomics Institute and are part of the Braingeneers group, where we collaborate across neuroscience, computation, and bioengineering to create new tools for understanding the brain.