Gregory Holmes, PhD

My overarching area of research interest employs a systems neuroscience approach to addressing pathophysiological changes in autonomic nervous system (e.g., gastrointestinal) functions following spinal cord injury (SCI) since 1991. My ongoing studies of post-SCI gastrointestinal (GI) dysfunction are revealing that substantial pathophysiological remodeling of GI reflex circuits occurs following injury. Specifically, in neurally-intact organisms, vagal afferents increase firing rate in response to local GI peptide release that is specific to the luminal contents of the gut. Furthermore, the gastric neurocircuitry located within the medulla is also responsive to the same peptides that have entered the circulation. At each of these points, sensitivity to an array of peptides (e.g., cholecystokinin, ghrelin) is significantly attenuated following SCI and provokes GI dysmotility. This suggests that the intrinsic circuitry of the GI tract is compromised after SCI even if it remains anatomically intact. My lab enjoys numerous collaborations in order to apply a multidisciplinary approach with validated molecular techniques, contemporary transcriptomic approaches (RNAsequencing, CRISPRi), whole cell patch electrophysiology, live cell calcium and voltage imaging, an ex vivo, vagally-innervated gastric preparation and in vivo gastric motility recording in order to fully dissect the role of ion channel dysfunction specific to vagal sensory neuropathy.