Sushil SarnaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA F1000 Section Head (since 10 January 2005)
BIOGRAPHYACADEMIC POSITION :
Dr Sushil Sarna is currently a Professor in the Division of Gastroenterology and Hepatology, Department of Internal Medicine at The University of Texas Medical Branch (UTMB) in Galveston.
My research interests include cell signaling and gene expression in gut inflammation, Functional Bowel Disorders, and in response to chronic psychological stress. We perform experiments on freshly dissociated and cultured smooth muscle cells obtained from the human and animal gut, integrated muscle strips and in conscious animals The objective is to identify key signaling molecules and their gene expression that regulate gut smooth muscle excitation-contraction coupling, excitation-inhibition coupling, excitation-transcription coupling, and neurotransmitter release from the enteric neurons. The alterations in excitation-contraction coupling make significant contributions to the symptoms of diarrhea, abdominal cramping, and urgency of defecation in inflammatory bowel disease and irritable bowel syndrome.
My lab uses cellular, molecular and biochemical approaches. Our focus is on transcriptional and translational changes that lead to alterations in the expression of L-type Ca2+ channels, myosin II, myosin light chain kinase, CPI-17,MLCK, Galphaq protein and changes in the expressions of nitric oxide (NO) and pro- and anti- inflammatory cytokines. Transcription factors NF-kappaB, SP-1, CREB and AP-1 mediate these some of these alterations. We investigate the role of smooth muscle cells in the secretion of cytokines, chemokines, and chemotactants in inflammation. This seems to be an important role of smooth muscle cells, whose normal function is to contract. By secreting these inflammatory mediators, the smooth muscle cells amplify the inflammatory response initiated by a relatively small number of resident and infiltrating immunocytes to induce permanent alterations in gene expression of excitation-contraction coupling proteins.
In recent publications, we have shown that many of the enteric neurotransmitters in the gut wall induce excitation-transcription coupling in smooth muscle cells. This seminal finding explains motility disorders in intestinal inflammation as well as in Functional Bowel Disorders. An additional area of interest in my lab is stress-induced gene expression in colonic circular smooth muscle cells, enteric neurons and dorsal root ganglia. My lab found that acute and chronic stressors differentially alter colonic smooth muscle function. More recently, studies in my lab focus on identifying the developmental origins of Functional Bowel Disorders and Inflammatory Bowel Disease. We have tested the hypothesis that an inflammatory or psychological insult during the formative stages of fetal and neonatal developments alters the epigenetic programming of critical genes, which persists into adulthood to cause the symptoms of Functional Bowel Disorders. The fetal and neonatal programming also alters immune responses and mucosal permeability in adulthood, which enhances inflammatory responses to subthreshold stimuli.
Our approach emphasizes translational research related to the diagnosis of motility disorders in inflammatory bowel disease, irritable bowel syndrome, and gastroparesis as well as to the development of therapeutic agents targeting pharmacological receptors, cell signaling molecules and epigenetic proteins. We have developed recently a rat model of post-infectious IBS, which mimics the motility dysfunction in human disease. This model shows that gene plasticity in colonic smooth muscle cells underlies motility dysfunction.
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