Past Research Awards
The AMS-Janssen Research Awards were provided to four young investigators to carry out research in the area of gastrointestinal motility. Research proposals were selected on the basis of potential impact on the understanding and treatment of disorders of gastrointestinal motility. Funding support of $25,000.00 was provided to each individual to support their research. Grants were selected on the basis of innovation and potential for future funding from other agencies.

Dr. Premysl Bercik

Dr. Premysl Bercik is currently a Post-doctoral Fellow in the Intestinal Diseases Research Programme at McMaster University in Hamilton, Ontario, Canada. After graduating from the Medical Faculty of Charles University in Prague, Czechoslovakia, in 1991, Dr. Bercik obtained a Doctoral degree in GI Physiology at the University of Lausanne, Switzerland in 1995. After a 3-year residency training at the General University Hospital and Central Military Hospital in Prague, Czech Republic, Dr. Bercik was certified in Internal Medicine in 1998.

Dr. Bercik’s project is entitled “Immune-driven model of functional gastrointestinal disorders”. Functional gastrointestinal diseases as IBS and NUD are among the most common disorders encountered by gastroenterologists. Motility disorders, visceral hypersensitivity and psychological factors have been considered as pathophysiological mechanisms. Inflammation releases many active substances, which can either directly activate peripheral nerve endings or, more probably, induce functional and structural alterations in sensory and motor neurons. It is plausible that gastrointestinal infection, either transient or chronic, may initiate a chain of events leading to a functional disorder. Dr. Bercik has proposed to study the effects of repeated exposure to luminal antigens on motor and sensory function in mice sensitized by previous infection by Trichinella spiralis and to investigate the mechanisms leading to chronic post-infective upper gut dysfunction in vivo.

Dr. Bercik has recently published several papers in this area.

Bercik P, De Giorgio R, Blennerhassett P, Verdu EF, Barbara G and Collins SM.
Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection. Gastroenterology. 123(4):1205-1215, 2002.

Verdu EF, Deng Y, Bercik P, Collins SM. Modulatory effects of estrogen in two murine models of experimental colitis. Am J Physiol Gastrointest Liver Physiol. 283:G27-G36, 2002.

Wang XY, Berezin I, Mikkelsen HB, Der T, Bercik P, Collins SM, Huizinga JD. Pathology of interstitial cells of Cajal in relation to inflammation revealed by ultrastructure but not immunohistochemistry. Am J Pathol. 160:1529-1540, 2002.

Huizinga JD, Berezin I, Sircar K, Hewlett B, Donnelly G, Bercik P, Ross C, Algoufi T, Fitzgerald P, Der T, Riddell RH, Collins SM, Jacobson K. Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system. Gastroenterology. 120: 561-567, 2001.

Der T, Bercik P, Donnely G, Jackson T, Berezin I, Collins SM, Huizinga J. Interstitial cells of Cajal and inflammation-induced motor dysfunction in the mouse small intestine. Gastroenterology 2000: 119: 1590-9.

Bercik P, Bouley L, Dutoit P. Blum AL, Kucera P. Quantitative analysis of intestinal motor patterns: spatio-temporal organization of nonneural pacemaker sites in the rat ileum. Gastroenterology 2000: 119: 386-94.

Verdu EF, Bercik P, Cukrowska B, Farre-Castany MA, Bouzourene H, Saraga E, Blum AL, Corthesy-Thelaz I, Tlaskalova-Hogenova H, Michetti P. Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice. Clin Exp Immunol 2000; 120:46-50.

Bercik P, Verdu EF, Armstrong D, Idstrom JP, Cederberg C, Markert M, Crabtree JE, Stolte M, Blum AL. The effect of ammonia on omeprazole-induced reduction of gastric acidity in subjects with Helicobacter pylori infection. Am J Gastroenterol 2000; 95: 947-55.

Dr. Greg Dick

Dr. Greg Dick is currently a Research Assistant Professor in the Department of Physiology & Cell Biology at the University Of Nevada School Of Medicine. After receiving a B.S. in Physiology from Oklahoma State University in 1991, Dr. Dick earned his Ph.D. in Physiology from the University Of Missouri School Of Medicine in 1996. He was a post-doctoral fellow with Dr. Kent Sanders and was funded by a National Research Service Award from NIDDK. Dr. Dick has recently accepted a position as Assistant Professor at Louisiana State University Health Sciences Center. Dr. Dick has received support from the AMS and a Beginning Grant-In-Aid from the American Heart Association (Western States Affiliate) for a grant entitled: “Tamoxifen, angiogenesis, and vascular reactivity” for $120,000.

Dr. Dick’s project is entitled “Investigation of the BK Channel b1 Subunit as a Novel Modulator of GI Motility”. BK channels are large conductance Ca2+/voltage-activated K+ channels that influence the electrical and mechanical activity of visceral organs. In smooth muscle, BK channels associate with a regulatory subunit, b1, that increases the Ca2+-sensitivity and alters pharmacological properties. For example, presence of the b1 subunit allows BK channels to be activated by estrogen in a non-genomic manner. Dr. Dick has found that tamoxifen, an estrogen receptor modulator, also activates BK channels in the presence of the b1 subunit. He has proposed to study the structural properties of the b1 subunit that confer sensitivity to estrogens and related molecules, as well as the functional impact of channel activation.

Dr. Dick has recently published several papers in this area.

Dick, G.M., A.C. Hunter, P.J. Cragg, and K.M. Sanders. Inhibition of volume-sensitive Cl- current by purinergic receptor antagonists in canine colonic smooth muscle. Molecular Pharmacology (submitted)

Dick, G.M., D.B. Lubahn, K.B. Murch, K.M. Sanders, and D.K. Bowles. Activation of smooth muscle K+ channels by tamoxifen in estrogen receptor a and b knockout mice. American Journal of Physiology: Endocrinology & Metabolism (in revision)

Cipleu, C.D., C.E. Palant, K.M. Sanders, and G.M. Dick. Separation of two Cl- currents in cultured human and murine mesangial cells: biophysical and pharmacological characteristics of ICl.vol and ICl.Ca. Journal of Vascular Research 39(5): 426-436, 2002.

Dick, G.M. The pure anti-oestrogen ICI 182,780 (FaslodexTM) activates large conductance Ca2+-activated K+ channels in smooth muscle. British Journal of Pharmacology 136: 961-964, 2002.

Dick G.M., A.C. Hunter, and K.M. Sanders. Ethylbromide tamoxifen, a membrane impermeant antiestrogen, activates smooth muscle calcium-activated large conductance potassium channels from the extracellular side. Molecular Pharmacology 61 (5): 1105-1113, 2002.

Dick, G.M. and K.M. Sanders. (Xeno)estrogen-sensitivity of smooth muscle BK channels conferred by the regulatory b1 subunit: A study of b1 knockout mice. Journal of Biological Chemistry 276 (48): 44835-44840, 2001.

Dick, G.M., C.F. Rossow, S. Smirnov, B. Horowitz, and K.M. Sanders. Tamoxifen activates smooth muscle BK channels through the regulatory b1 subunit. Journal of Biological Chemistry 276 (37): 34594-34599, 2001.

Dr. Tamas Ordog

Dr. Tamas Ordog is currently a Research Assistant Professor in the Department of Physiology and Cell Biology at the University of Nevada, Reno School of Medicine. Dr. Ordog earned his M.D. from the University of Pécs Medical School (Hungary) in 1988, where he became a Research Fellow of the Hungarian Academy of Sciences in 1989. He received further training in Dr. Ernst Knobil’s Laboratory for Neuroendocrinology at The University of Texas–Houston Medical School as a Postdoctoral Research Fellow (1992-1994) and Senior Fellow (1994-1997). He joined the Department of Physiology and Cell Biology at the University of Nevada, Reno School of Medicine in 1997.

Dr. Ordog’s project is entitled “A Model to Study Entrainment of Gastric Pacemakers”. Gastric peristalsis requires orderly propagation of electrical slow waves, down a steep frequency gradient, from the dominant pacemaker in the orad corpus toward the pylorus. Damage to electrical pacemaking or slow wave propagation can lead to dysrhythmias and delayed gastric emptying in a variety of disorders including diabetes mellitus. Interstitial cells of Cajal (ICC) have been shown to generate and propagate slow waves in the gastric corpus and antrum but the mechanisms responsible for the integration of their disparate frequencies are unclear. Dr. Ordog has proposed to develop an in vitro model of pacemaker entrainment by co-culturing ICC purified from murine gastric corpus and antrum by a novel approach and to utilize this system to study the mechanisms of integration of pacemaker activity.

With the aid of this Research Grant Award, Dr. Ordog has recently obtained an R01 grant from the National Institute of Diabetes, Digestive and Kidney Diseases (“Interstitial Cells of Cajal in Diabetic Gastropathy”). One of the major goals of this NIH grant is to further investigate the role of impaired pacemaker entrainment in the generation of gastric arrhythmias and resultant gastroparesis. Results that arose from Dr. Ordog’s Research Grant Award have also been published as a full paper and in abstract form:

Ordog T, Baldo M, Danko R, and Sanders KM. Plasticity of electrical pacemaking by interstitial cells of Cajal and gastric dysrhythmias in W/WV mutant mice. Gastroenterology 123: 2028-2040, 2002.

Ordog T, Redelman D, Miller LJ, Horowitz NN, Zhang Q, Horowitz B, and Sanders KM. Approaches to purification of interstitial cells of Cajal. Neurogastroenterol Mot 14: 442-443, 2002. (American Neurogastroenterology and Motility Society Young Investigator Award)

Other papers Dr. Ordog has published in this field:

Ordog T, Takayama I, Cheung WKT, Ward SM, and Sanders KM. Remodeling of networks of interstitial cells of Cajal in a murine model of diabetic gastroparesis. Diabetes 49: 1731-1739, 2000.

Ward SM, Ordog T, Koh SD, Abu Baker S, Jun JY, Amberg G, Monaghan K, and Sanders KM. Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. Journal of Physiology (London) 525: 355-361, 2000.

Ordog T, Ward SM, and Sanders KM. Interstitial cells of Cajal generate electrical slow waves in the murine stomach. Journal of Physiology (London) 518: 257-269, 1999.

Dr. Xuan-Zheng Shi

Dr. Xuan-Zheng Shi is currently an Assistant Professor in the Department of Medicine (Division of Gastroenterology) at the University of Texas Medical Branch. Dr. Shi earned his M.D. from Wannan Medical College, China in 1984. He was a lecturer in medical physiology for five years at Lanzhou Medical College, and his research focused on gastrointestinal motility. In 1992, Dr. Shi moved to the Department of Physiology at the Medical College of Wisconsin and studied molecular biology for two years before joining Dr. Sushil Sarna’s team in 1994.

Dr. Shi’s project is entitled “The Secretory Function of Colonic Smooth Muscle Cells”. NF-kB is a proinflammatory transcription factor, whose activation leads to expression of many genes encoding cytokines, chemokines, and other inflammatory mediators. Dr. Shi has found that NF-kB is present in the colonic circular smooth muscle cells and is activated during inflammation. The proposed project will investigate cytokine/ chemokine -secreting function of human colonic smooth muscle cells upon activation by NF-kB. He has also proposed to study the autocrine effects of these secreted cytokines, chemokines, and other inflammatory mediators on smooth muscle contractility.

Dr. Shi has recently published several papers in this area:

Shi, XZ, P. F. Lindholm, and S. K. Sarna. NF-kB Activation By Oxidative Stress and Inflammation Supresses Contractility in Canine Colonic Circularmooth Muscle Cells. Gastroenterology 124 (5), 2003.

Shi, XZ and SK Sarna. Impairment of Ca2+ mobilization in circular muscle cells of the inflamed colon. Am. J. Physiol. (Gastrointest. Liver Physiol 41): G234 -G242, 2000.

Shi, XZ and SK Sarna. Differential inflammatory modulation of canine ileal longitudinal and circular muscle cells. Am. J. Physiol. (Gastrointest. Liver Physiol. 40): G341 -G350, 1999.

Shi, XZ, and SK Sarna: Inflammatory Modulation of Muscarinic Receptor Activation in Canine Ileal Circular Muscle Cells. Gastroenterology 112:864-874, 1997.