Dr. John Grider
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Contact Information
Department of Physiology and Biophysics Virginia Commonwealth University P.O. Box 980551 Richmond, Virginia 23298-0551 Tel: 804-828-1853 Fax: 804-828-7382 email: jgrider@vcu.edu |
John R. Grider completed his B.A. in Biology in 1974 at the University of Pennsylvania and his Ph.D. in Physiology and Biophysics in 1981 at Hahnemann University (now Drexel University School of Medicine). He did an NIH postdoctoral fellowship in Gastrointestinal Physiology with Gabriel Makhlouf, M.D., Ph.D. at the Medical College of Virginia from 1981 through 1983. He joined the department in 1984.
Research
The main goal of our laboratory is understanding the enteric nervous system and how it regulates the contraction and relaxation of the gut smooth muscle in a coordinated manner. Much of our work has focused on identifying the main neurotransmitters released from neurons of the enteric nervous system and constructing models of neural circuits within the enteric nervous system based on the action of these transmitters. We have focused on the peristaltic reflex which underlies peristalsis, the main propulsive activity of the gut. Initial studies identified excitatory and relaxant neurotransmitters and characterized the signaling pathways that they activated in smooth muscle cells. More recently we have examined the complex sensory pathways that initiate the peristaltic reflex. We demonstrated that stretch activates extrinsic sensory neurons that originate in the dorsal root ganglia whereas responses to luminal stimuli (movement of intestinal villi or components of the chyme) are mediated by release of serotonin from enteroendocrine cells that, in turn, activate 5-HT4 receptors on enteric sensory neurons that release calcitonin gene-related peptide. Our latest studies have demonstrated that this latter sequence is enhanced by a unique rapid action of the neurotrophin, Brain Derived Neurotrophic Factor (BDNF). We are currently studying the growth of enteric neurons in tissue culture to determine the role of various cytokines and neurotrophins in guiding enteric neurons to the correct targets, thereby establishing circuits within the enteric nervous system. This has importance in the embryonic development of the gut and in understanding the re-establishment of correct circuits following pathologies. We are also continuing to examine the role of various neurotransmitters as modulators of the sensory and motor limbs of the peristaltic reflex. We are also actively studying the changes in nerve-muscle function and in enteric neural circuits following inflammatory bowel disease. A wide range of techniques from molecular and cellular biological approaches to nerve-muscle tissue culture to intact organ based physiology preparations are employed in our research. This work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases for over 20 years.
Teaching
I am actively involved in the teaching of graduate and medical students at VCU. I lecture on gastrointestinal physiology in the first year medical physiology course and in the graduate mammalian physiology course. In addition, I lecture on enteric neuromuscular function in Cell and Molecular Neuroscience and in Cell Physiology courses as well as in several advanced physiology courses on cell signaling and on sensory neurophysiology. My lab is actively involved in the research training of undergraduate, graduate, and medical students as well as postdoctoral research fellows and clinical fellows from the Department of Surgery, and the Department of Medicine, Division of Gastroenterology. I am a member of several NIH training grants, the MD/PhD training program, and the VCU Academy of Mentors.
Selected Publications
Gianino S, Grider, JR, Cresswell J, Endomoto H, and Heuckeroth, RO. GDNF determines enteric neuron numbers by controlling precursor proliferation. Development 130:2187-2198 2003. PubMed
Grider, JR. Neurotransmitters mediating the intestinal peristaltic reflex in the mouse, J Pharmacol and Exptl. Therap 307: 460-467, 2003. PubMed
Bornstein, JC, Costa M, Grider JR. Enteric motor and interneuronal circuits. Neurogastroenterology and Motility 16 (Suppl 1): 34-38, 2004.
Grider, JR. Desensitization of the peristaltic reflex induced by mucosal stimulation with the elective 5-HT4 agonist Tegaserod. Am J Physiol 290:G319-G327, 2006. PubMed
Grider, JR, Piland, BE, Gulick, M, and Qiao, LY. Brain-derived neurotrophic factor augments the peristaltic reflex by augmenting serotonin and calcitonin gene-related peptide release. Gastroenterology 130:771-780, 2006.PubMed
Grider, JR, Piland, BE. The peristaltic reflex induced by short chain fatty acids is mediated by sequential release of 5-HT and neuronal CGRP but not BDNF. Am J Physiol : 292: G429-437, 2007. PubMed
Affiliate Listings
Department of Internal Medicine, Division of Gastroenterology
VCU Program in Enteric Neuromuscular Sciences (VPENS)