ION CHANNEL AND NEUROTRANSMITTER RECEPTOR FUNCTION IN EPILEPSY
Epilepsy is a devastating neurological disorder characterized by the occurrence of spontaneous seizures. Seizures, which fundamentally reflect hyperexcitability in neural networks, manifest at the cellular, microcircuit, and the systems level and are captured well by diverse model systems. This allows us to probe the consequences of epilepsy-related genetic variants at multiple levels of complexity and to make comparisons across rodent and human cell model systems. We are currently exploring the role of voltage gated sodium channels and glutamate receptors in early-life epilepsies.
ENGINEERING HUMAN CELL MODELS OF NEUROLOGICAL DISEASES
The Makinson lab uses 3D cell culture models of the developing brain derived from human induced pluripotent stem cells (hiPSC) to study neurodevelopmental disorders. We generate and functionally characterize these microphysiological systems using a diverse set of complementary approaches including single cell transcriptomic profiling, large-scale network imaging, and multi-channel extracellular and intracellular electrophysiology.
NETWORK-SCALE FUNCTIONAL IMAGING AND MANIPULATION OF DEVELOPING NEURAL CIRCUITS
The Makinson lab leverages recent advances in functional imaging, genetically encoded fluorescent indicators (including calcium and voltage indicators) optogenetic tools, and photolabile compounds to survey and manipulate large networks of cells. This enables us to assess the activity of ensembles of neurons during normal and pathological states of activity in human brain organoid and rodent models of neurological disease.