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David R. Brown, Ph.D. Professor, Department of Veterinary Pathobiology E-mail: brown013@umn.edu

Research Interests:

The intestinal mucosa represents the largest body surface area exposed to the external environment. It is under the control of the enteric nervous system, an independent branch of the autonomic nervous system that operates independently of central nervous system.

My laboratory is investigating the mechanisms by which the enteric nervous system modulates host defense processes in the intestinal mucosa. We are examining the chemical coding and function of enteric neurons that innervate the gut-associated lymphoid tissue, including Peyer's patches, which are organized lymphoid follicles in the wall of the small intestine that are the inductive site for mucosal immunity. We have discovered that drugs which inhibit enteric neurotransmission modulate internalization of pathogenic bacteria such as Salmonella enterica and E. coli O157:H7 into both Peyer's patches and the non-follicular absorptive epithelium of the intestine. Moreover, norepinephrine acting through protein kinase A-coupled alpha-adrenergic receptors has been shown to promote E. coli O157:H7 adherence to the colonic mucosa. Recently, we have discovered that several classes of enteric neurotransmitters regulate the release of secretory immunoglobulin A onto the mucosal surface. Finally, our studies indiocate that enteric neurons expressing opioid receptors with novel pharmacological characteristics modulate immediate hypersensitivity reactions in the intestinal mucosa. Hypothesis-driven research in my laboratory is conducted primarily at the molecular, cellular, and tissue levels using an array of cutting-edge approaches.

Selected Publications:

Schmidt LD, Kohrt LJ, Brown DR. Comparison of growth phase on Salmonella enterica serovar Typhimurium invasion in an epithelial cell line (IPEC J2) and mucosal explants from porcine small intestine. Comp Immunol Microbiol Infect Dis. 2008 Jan;31(1):63-9. Epub 2007 Jun 4.

Schreiber KL, Price LD, Brown DR. Evidence for neuromodulation of enteropathogen invasion in the intestinal mucosa. J Neuroimmune Pharmacol. 2007 Dec;2(4):329-37.

Brown DR, Price LD. Catecholamines and sympathomimetic drugs decrease early Salmonella Typhimurium uptake into porcine Peyer's patches. FEMS Immunol Med Microbiol. 2007 Nov 19.

Chen, C., M. Lyte, M. P. Stevens, L. Vulchanova and D.R. Brown:
Mucosally-directed adrenergic nerves and sympathomimetic drugs
enhance non-intimate adherence of Escherichia coli O157:H7 to
porcine cecum and colon. Eur. J. Pharmacol., 539: 116-124, 2006.

Schreiber, K.L. and D.R. Brown: Adrenocorticotrophic hormone
modulates Escherichia coli O157:H7 adherence to porcine colonic
mucosa. Stress, 8:185-190, 2005.

Former Graduate Students:

Kristin Schreiber (Ph.D. 2004, Neuroscience, University of Minnesota).