Circuits in the Crossfire of Inflammation

We study how immune and metabolic pathways interact to maintain, or destabilize, the cellular and synaptic organization of the brain. By reconstructing human neural networks from stem cells, our goal is to uncover how inflammation propagates across cells and circuits, leading to dysfunction in neurodegenerative diseases such as Alzheimer’s disease.

Our approach begins with human induced pluripotent stem cells (iPSCs), which we engineer into complex, multicellular brain models containing neurons and glia. Using CRISPR-based perturbations, live imaging, and multi-omic profiling, we define how genetic and environmental risk factors alter glial signaling, metabolic flexibility, and intercellular communication. By combining these tools with functional network readouts, including calcium imaging, electrophysiology, and optogenetics, we map how inflammatory cues reshape connectivity and network dynamics.

A major focus of the lab is to define the causal links between cellular inflammation and circuit dysfunction. We investigate how glia sense neuronal activity, how their metabolic states influence cytokine production, and how chronic inflammatory feedback loops emerge across the brain. We also integrate data from post-mortem human tissue to anchor our in vitro findings within the architecture of the diseased human brain.

Through this work, we aim to build a new framework for understanding neurodegeneration, not as the isolated failure of neurons, but as a systems-level collapse of communication between cells, circuits, and immune networks. By engineering the human brain in vitro, we seek to reveal the cellular logic by which inflammation drives dysfunction and to identify points of resilience that can be harnessed for therapy.