Jackie D. Wood, Ph.D.

Professor Physiology and Cell Biology Internal Medicine 305D Hamilton Hall 1645 Neil Avenue Columbus  OH  43210-1218 wood.13@osu.edu

Education:
B.S., Biology, Kansas State University, Pittsburg, KS
M.S., Biology/Physiology, Kansas State University, Pittsburg, KS
Ph.D., Physiology and Biophysics, University of Illinois, Urbana, IL

The general orientation of investigative work in my laboratory is a continuous effort at moving forward our understanding of the neurobiology of the enteric nervous system, which is an independent integrative nervous system often referred to as the “brain-in-the-gut”. Three major projects are currently underway:
 

1: Corticotropin Releasing Factor and Stress

This project investigates the role of corticotropin releasing factor in the enteric nervous system in relation to symptoms of the irritable bowel syndrome (IBS) and brain-gut interactions during   psychogenic stress. This work aims to understand how release of corticotropin releasing factor (CRF) in the enteric nervous system (ENS) and ENS interactions with mast cells during stress are transformed into symptoms of cramping abdominal pain, fecal urgency and watery diarrhea, which are hallmarks of diarrhea-predominant irritable bowel syndrome (d-IBD), infectious enteritis, food allergy, and inflammatory bowel disease (IBD) in humans. Psychogenic stress evokes and exacerbates the symptoms of d-IBS and IBD. Integration of multiple methods will be used to clarify the neurobiology of CRF in the ENS including: 1) intraneuronal electrophysiology combined with morphological and functional identification of single neurons; 2) immunohistochemical identification and localization of receptors and transmitters expressed by the identified neurons; 3) laser-capture and isolation of enteric neurons for real time RT-PCR analysis; 4) selective gene silencing by in vivo RNA interference 5) Ussing chamber technology; 6) organ bath pharmacology; 7) whole animal intestinal transit and secretion.

2: Purinergic Neurotransmission in the Enteric Nervous System

The overall aim of this project is to characterize a novel purinergic slow excitatory postsynaptic potential (EPSP) that is mediated by a metabotropic ATP receptor (P2Y1 receptor) in the enteric nervous system. Evidence for the existence of the purinergic slow EPSP comes from studies in which the P2Y1 receptor antagonist MRS2179 was found to selectively block both the slow EPSP and slow EPSP-like responses evoked by ATP in submucosal neurons. The hypothesis that the purinergic slow EPSP is mediated by synaptic release of ATP and P2Y1 receptors in submucosal secretomotor neurons is supported by pharmacological evidence obtained from morphologically identified neurons. Molecular cloning and functional expression has been used to characterize the P2Y1 receptor.  We find that intestinal secretomotor neurons receive purinergic slow excitatory synaptic input from neurons in the myenteric plexus, from neighboring neurons in the submucosal plexus and from sympathetic neurons in prevertebral ganglia. Moreover, we have discovered that the selective P2Y1 receptor antagonist MRS2179  suppresses neurogenic secretory responses evoked by application of ATP and by transmural electrical stimulation of secretomotor neurons in Ussing chamber experiments. This work was the first to demonstrate a functional purinergic slow EPSP in the enteric nervous system. The discovery that a P2Y1 receptor mediates the slow EPSP in intestinal secretomotor neurons is expected to translate into development of new drugs for treatment of the irritable bowel syndrome,  inflammatory bowel disease and other disorders of defecation by targeting the P2Y1 receptor or ATP metabolic pathways in the pool of enteric neurons that control intestinal secretion.

3. Signal Transduction in the Enteric Nervous System

This is project investigates the cellular biology of secretomotor neurons in the intestinal submucosal plexus and musculomotor neurons in the myenteric plexus of guinea-pig intestine.  The cellular neurobiology underlies functions of secretomotor neurons that are basic to control of fluidity of the intestinal contents in states of health and to diarrhea and constipation in disordered states.  Cellular neurobiology of musculomotor neurons is basic to the control of muscular contractile behavior during patterns of intestinal motility.  We have discovered that  slow synaptic and paracrine signaling in enteric motor neurons is specialized and differs from this form of signaling in other kinds of enteric neurons (e.g., AH-Dogiel morphologic Type II myenteric neurons).  The results for noncholinergic secretomotor neurons in the submucosal plexus and ascending and descending musculomotor neurons in the myenteric plexus shows that these neurons express in common  the properties of uniaxonal morphology, S-type electrophysiologic behavior, increased ionic conductance during slow synaptic excitation and a signal transduction cascade that  involves calmodulin kinase II, but not  protein kinase A.   Common expression of calmodulin kinase II for in the pilot studies on this group of neurons suggests mechanisms of signal transduction that differs from the more extensively studied mechanism of stimulation of adenylate cyclase and elevation of cAMP as an intraneuronal second messenger in myenteric AH-type neurons.

Current Grants:
• "Bradykinin in Enteric Neuroimmune Communication", NIH R01 DK57075, $1,658,250, 2001-2006
• "Function of the Enteric Nervous System", NIH R01 DK37238, $1,650,000, 2003-2008
• "Purinergic Neurogenic Mucosal Secretion", NIH R01 DK068258, $1,681,000, 2004-2009
• "Actions of Tegaserod in the Enteric Nervous System", Novartis Pharmaceuticals Corporation, $209,395, 2003-2006

Publications: 
• Liu S, Gao X, Gao N, Wang X, Fang X, Hu H-Z, Wang G-D, Xia Y, Wood JD. Expression of type 1 corticotropin releasing factor receptor (CRF₁) in the guinea-pig enteric nervous system. J Comp Neurol 2005; 481(3):284-298.
• Wang G-D, Wang X-Y, Hu H-Z, Fang X, Liu S, Gao N, Xia Y, Wood JD. Angiotensin Receptors and Actions in Guinea-Pig Enteric Nervous System. Am J Physiol 2005; 289:G614-626.
• Liu S, Gao N, Hu H-Z, Wang X-Y, Wang G-D, Fang X, Gao X, Xia Y, Wood JD. Distribution and chemical coding of corticotropin releasing factor-immunoreactive neurons in the guinea-pig enteric nervous system. J Comp Neurol 2006; 494:63-74.
• Wood JD. Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies. Gut 2006; 55:445-447.
• Hu HZ, Xiao R, Wang C, Gao N, Colton CK, Wood JD, Zhu MX. Potentiation of TRPV3 channel function by unsaturated fatty acids. J Cell Physiol 2006; 208:201-212.
• Gao N, Hu HZ, Zhu MX, Fang X, Liu S, Gao C, Wood JD. The P2Y purinergic receptor expressed by enteric neurones in guinea-pig intestine. Neurogastroenterol Motil 2006; 18:316-323.
• Fang X, Hu HZ, Gao N, Liu S, Wang GD, Wang XY, Xia Y, Wood JD. Neurogenic secretion mediated by the purinergic P2Y(1) receptor in guinea-pig small intestine. Eur J Pharmacol 2006; 536:113-122.
• Wood JD. The enteric purinergic P2Y(1) receptor. Curr Opin Pharmacol 2006; 6(6):564-70.
• Wood JD. Targeting functional gastrointestinal disorders. Curr Opin Pharmacol 2006; 6(6):533-535.
• Gao N, Hu HZ, Liu S, Gao C, Xia Y, Wood JD. Stimulation of Adenosine A1 and A2A Receptors by Adenosine 5'-monophosphate (AMP) in the Submucosal Plexus of Guinea-pig Small Intestine. Am J Physiol Gastrointest Liver Physiol 2007; 292:G492-500.
• Wang GD, Wang XY, Hu HZ, Liu S, Gao N, Fang X, Xia Y, Wood JD. Inhibitory Neuromuscular Transmission Mediated by the P2Y1 Purinergic Receptor in Guinea-Pig Small Intestine. Am J Physiol Gastrointest Liver Physiol 2007; 292:G1483-489.
• Wood JD. Neuropathophysiology of functional gastrointestinal disorders. World J Gastroenterol 2007; 13:1313-1332.
• Wood JD. Effects of bacteria on the enteric nervous system: Implications for the Irritable Bowel Syndrome. J Clin Gastroenterol 2007;41: Suppl 1:S7-S19.
• Mutafova-Yambolieva VN, Hwang SJ, Hao X, Chen H, Zhu MX, Wood JD, Ward SM, Sanders KM. _-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Proc Natl Acad Sci USA 2007; 104:16359-64.
• Fang X, Liu S, Wang X-Y, Gao N, Hu H-Z, Wang G-D, Cook CH, Needleman BJ, Mikami DJ, Xia Y, Fei G-J, Hicks GA, Wood JD. Neurogastroenterology of tegaserod (HTF 919) in the submucosal division of the guinea-pig and human enteric nervous system. Neurogastroenterol Mot 2008; 20(1):80-93.