Brian Wainger

Brian Wainger

Assistant Professor of Anaesthesia
Brian Wainger

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. Patch clamp analysis of the motor neurons led to the identification of a novel therapeutic candidate, which is currently the focus of a 12-center, randomized, double-blind clinical trial with neurophysiological measures of cortical and motor neuron excitability 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. In addition, we are defining the channels and molecular processes that contribute to motor neuron excitability in primary mouse and human iPSC-derived motor neurons. We are also using in vitro motor neuron excitability as a screening tool to identify and evaluate novel therapeutics.

On the sensory neuron front, we developed a lineage 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 ionotropic 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.

We are active within the Neurology and Anesthesia, Critical Care & Pain Medicine Departments within Massachusetts General Hospital, and we use patient samples and post-mortem tissue to evaluate hypotheses generated in our in vitro studies. We are also a core group within the Harvard Stem Cell Institute.

Contact Information

MassGeneral Institute for Neurodegenerative Disease
114 16th Street, Room 2007
Building 114, Charlestown Navy Yard
Charlestown, MA 02129
p: 617-724-1726