Proteomics and In Vitro Studies

Proteomics and Protein Biochemistry: Sodium channels play key roles in signal transduction and transmission that underlie pain. But they do not function in isolation and in fact work in concert with partner molecules. We have very strong capabilities in sodium channel proteomics and protein biochemistry for the discovery of new protein-protein interactions and intracellular channel trafficking. We have recently established a Tandem Affinity Purification approach for the identification of sodium channel partners. Our affiliation with Yale University enables full access to the proteomics infrastructure within the university and to the Yale Keck Proteomics Core facility, including protein identification by Mass Spectrometry. We routinely validate newly discovered protein-protein interactions in cell lines via GST-pull down assays, co-IPs, fluorescence energy transfer (FRET), and co-localization studies by confocal microscopy.

DRG Neuron Culture: We have pioneered the use of primary sensory neurons as expression systems to assess the effects of sodium channel variants on gating properties of these channels and on the firing properties of the neurons in which they are expressed, and to assess response to various agents for drug screening. Highly experienced technicians provide our physiologists and pharmacologists with a pipeline of transfected as well as non-transfected cells as needed, thus optimizing our research efficiency. Our high throughput cell culture facility and expertise in DRG neuron phenotyping enable detailed studies of pain pathophysiology and poise us for high-resolution preclinical assessments of the efficacy of sodium channel blockers.

Stem Cell Technology: We have a well-established platform that enables us to routinely develop patient-specific iPSC-derived sensory neurons as a “disease-in-a-dish” model. The model contains the entire genome of the human subject under study, and is invaluable for investigating the pathophysiological basis of pain due to specific channel mutations, and as a cellular platform to test the efficacy of existing and novel sodium channel blockers, and for the study of factors that confer pain resilience.