Dr. Gregory Holmes' overarching area of research interest employs a systems neuroscience approach to addressing two key pathophysiological changes in autonomic nervous system (e.g., gastrointestinal) functions following spinal cord injury (SCI).

First, Dr. Holmes' ongoing studies of post-SCI gastrointestinal (GI) dysfunction are revealing that substantial pathophysiological remodeling of GI reflex circuits occurs following injury. Specifically, vagal afferents form the intrinsic circuitry necessary for the gastric reflexes during digestion. The sensitivity of these afferents is diminished after SCI even though vagal innervation remains anatomically intact. One emerging mechanism leading to vagal afferent hyposensitivity appears to involve voltage-gated channelopathy that reduces the initiation and propagation of digestion-associated action potentials within vagal afferents following SCI.

The Holmes lab's data support the emerging notion that the profound changes to the entire physiology following SCI merits focused investigation, and that SCI is a systemic injury beyond the spinal tissue.

Dr. Holmes' second area of research addresses a vastly understudied co-morbidity following SCI that is referred to as neurogenic bowel. Neurogenic bowel is a persistent challenge to the well-being and social reintegration of individuals with SCI. Insights from other fields of GI dysfunction (e.g., irritable bowel) suggests that pathophysiological remodeling of enteric neural circuitry is one mechanism contributing to the reduced colonic transit reported after SCI. The Holmes lab has identified anatomical and functional remodeling of the colonic neuromuscular interface in response to SCI. The enteric nervous system circuit is the final common pathway to the smooth muscle, and remodeling of this circuit will profoundly affect any extrinsic input from spinal autonomic motor neurons.

Addressing the changes in enteric and central nervous system neurocircuitry is critical to better understand the neural mechanisms leading to neurogenic bowel in the SCI population.