Sushil Sarna, Ph.D.
Professor, Division of Gastroenterology and Hepatology
Sushil Sarna, Ph.D.
Department of Internal Medicine
University of Texas Medical Branch
301 University Blvd.
Galveston, TX 77555-0764
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. Dr. Sarna earned his B.E. degree from Delhi School of Engineering in Delhi, India. He earned his M.S. degree and Ph.D. degrees from The University of Alberta Edmonton, Canada.
He is a member of the American Physiological Society, American Gastroenterological Association, American Motility Society, elected its Secretary, Councilor and President 1995-2002, International Motility Society, elected Member and Chair, 1993-2001. He is also the Director of Research, Division of Gastroenterology.
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, Gαq protein and changes in the expressions of nitric oxide (NO) and pro- and anti- inflammatory cytokines. Transcription factors NF-κB, 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.
One of our new initiatives is to use epigenetic tools in investigations of GI complications of diabetes – impaired gastric emptying and colonic motor function. We use the established animal models of type 2 diabetes. We are also developing models of neonatal injury to investigate epigenetic dysregulation in adult diabetes.
- Gonzalez, A., and Sarna, S.K. Neural regulation of in vitro giant contractions in the rat colon. American Journal of Physiology-Gastrointestinal and Liver Physiology 44: G275-G282; 2001.
- Johnson, C.P., Sarna, S.K., Zhu, Y.-R., Buchmann, E., Bonham, L., Telford, G.L., Roza, A.M., Adams, M.B. Effects of intestinal transplantation on postprandial motility and regulation of intestinal transit. Surgery. 2001 Jan;129(1):6-14.
- Liu, X., Rusch, N.J., Striessnig, J., Sarna, S.K. Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon. Gastroenterology. 2001 Feb;120(2): 480-9.
- Gonzalez, A., Sarna, S.K. Different types of contractions in rat colon and their modulation by oxidative stress. Am J Physiol Gastrointest Liver Physiol. 2001 Apr; 280(4): G546-54.
- Goldblatt, M.I., Swartz-Basile, D.A., Choi, S.-H., Rafiee, P., Nakeeb, A., Sarna, S.K., Pitt, H.A. Iron deficiency transiently suppresses biliary neuronal nitric oxide synthase. J Surg Res. 2001 Jun 15;98(2):123-8.
- Gonzalez, A., Sarna, S.K. Neural regulation of in vitro giant contractions in the rat colon. Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1): G275-82.
- Ali, I., Sarna, S.K. Selective modulation of PKC isozymes by inflammation in canine colonic circular muscle cells. Gastroenterology. 2002 Feb;122(2):483-94.
- Goldblatt, M.I., Choi, S.-H., Swartz-Basile, D.A., Nakeeb, A., Sarna, S.K., Pitt, H.A. Iron deficiency suppresses ileal nitric oxide synthase activity. J Gastrointest Surg. 2001 Jul-Aug; 5(4):393-400.
- Li, M., Johnson, C.P., Adams, M.B., Sarna, S.K. Cholinergic and nitrergic regulation of in vivo giant migrating contractions in rat colon. Am J Physiol Liver Physiol. Sep;283(3):G544-52.
- Sarna, S.K. Neuronal locus and cellular signaling for stimulation of ileal giant migrating and phasic contractions. Am J Physiol Gastrointest Liver Physiol. 2003 May;284(5):G789-97. Epub 2002 Dec 27.
- Saada, N., Dai, B., Echetebu, C., Sarna, S.K., Palade, P. Smooth muscle uses another promoter to express primarily a form of human Cav1.2 L-type calcium channel different from the principal heart form. Biochem Biophys Res Commun. 2003 Feb 28;302(1):23-8.
- Shi, X-Z, Lindholm, P.F., Sarna, S.K. NF-ï«B activation by oxidative stress and inflammation suppresses contractility in colonic circular smooth muscle cells. Gastroenterology. 2003 May;124(5):1369-80.
- Shi, X-Z., Sarna, S.K. G protein-mediated dysfunction of excitation-contraction coupling in ileal inflammation. Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G899-905.
- Pazdrak, K; Shi, X-Z., Sarna, S.K. TNFï¡ suppresses human colonic circular smooth muscle cell contractility by SP1- and NF-kappaB-mediated induction of ICAM-1. Gastroenterology. 2004 Oct;127(4):1096-109.
- Shi, X-Z., Sarna, S.K. Transcriptional regulation of inflammatory mediators secreted by human colonic circular smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. 2005 Aug;289(2):G274-G284.
- Shi, X-Z., Pazdrak, K., Saada, N.I., Dai, B., Palade, P., Sarna, S.K. Negative transcriptional regulation of human colonic smooth muscle Cav1.2 channels by p50 and p65 subunits of nuclear factor-kappaB. Gastroenterology. 2005 Nov; 129(5):1518-32.
- Micci, M-A., Kahrig, K.M., Simmons, R.S., Sarna, S.K, Espejo-Navarro, M.R. Pasricha, P.J. Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice. Gastroenterology. 2005 Dec;129(6):1817-24.
- Sarna, S.K. Molecular, functional and pharmacological targets for the development of gut promotility drugs. Am. J. Physiol. Gastrointest. Liver Physiol. 2006 Oct;291(4):G545-55.
- Hoogerwerf, WA, Sarna, S.K. Tachykinin recpetors as drug targets for motility disorders. Dig. Dis. 2006;24(1-2):83-90.
- Sarna, S.K. Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain. Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G572-81.
- Shi, XZ, Choudhury, BK, Pasricha, PJ, and Sarna, SK. A novel role of VIP in colonic motility function: induction of excitation-transcription coupling in smooth muscle cells. Gastroenterology. 2007 Apr;132(4): 1388-400.
- Sarna, SK. Are interstitial cells of Cajal plurifunction cells in the gut? Am J Physiol Gastrointest Liver Physiol. 2008 Feb. 294(2):G372-90. Review. Erratum in: Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1299.
- Shi XZ, Sarna, S.K. Gene therapy of Cav1.2 channel with VIP and VIP receptor agonists and antagonists: a novel approach to designing promotility and antimotility agents. Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G187-G196. Epub 2008 May 8. PMCID2494720.
- Sarna, S.K. Novel aspects of enteric regulation of colonic motility. Eur Rev Med Pharmacol Sci. 2008 Aus;12 Suppl 1:134.
- Choudhury, BK, Shi, XZ, Sarna, S.K. Gene plasticity in colonic circular smooth muscle cells underlies motility dysfunction in a model of postinfective IBS. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G632-642. Epub 2009 Jan.8. PMCID2660181.
- Li, Q., Sarna, S.K. Nuclear myosin II regulates the assembly of preinitiation complex for ICAM-1 gene transcription. Gastroenterology. 2009 Sept; 137(3):1051-60, e1-3. Epub 2009 Mar 26. PMCID2736361.
- Choudhury, BK, Shi, XZ, Sarna, S.K. Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function. Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1238-47. Epub 2009, Apr 9. PMCID2697948.
- Shi, XZ, Sarna, S.K. Homeostatic and Therapeutic Roles of VIP in Smooth Muscle Function: Myo-Neuro-Immune Interactions. Am J Physiol Gastrointest Liver Physiol. 2009 Aug 6. (Epub ahead of print). PMCID2763800.
- Winston, J.W., Xu, Guang-Yin, Sarna, S.K. Adrenergic stimulation mediates visceral hypersensitivity to colorectal distension following heterotypic chronic stress. Gastroenterology, 2010. Jan;138(1):294-304.e3. Epub 2009, Oct 1. PMCID2813397.