Our lab fuses electrophysiology and stem cell biology in order to explore how abnormal physiology contributes to diseases of the motor and sensory nervous systems. We use primary mouse motor neurons as well as motor neurons derived from human induced pluripotent stem cells (iPSCs).

Working with motor neurons made from amyotrophic lateral sclerosis (ALS) patients and healthy controls, we performed electrophysiological characterization and identified motor neuron hyperexcitability in ALS patient-derived motor neurons. Analysis of the motor neurons led to the identification of a novel therapeutic candidate, which is currently the focus of a 12-center clinical trial with neurophysiological measures as outcomes. Within this clinical trial, we are generating subject stem cell-derived motor neurons, and we are determining whether in vitro motor neuron electrophysiological properties are predictive of clinical indices of motor neuron excitability. We are also using in vitro motor neuron excitability as a screening tool to identify and evaluate novel therapeutics in the context of personalized or targeted medicine.

On the sensory neuron front, we developed a reprogramming technique for derivation of pain sensing (nociceptor) neurons from mouse and human fibroblasts. By comparing primary mouse and induced nociceptor neurons, we showed that the technique recapitulates many of the quintessential nociceptor receptors, channels and pathophysiological molecular pathways. This technology has already revealed novel insights through disease modeling of familial dysautonomia and promises to be valuable in the development of drug screens using human neurons. We are continuing to use this technique to investigate different painful neuropathies.