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Karen M. Harnett Adjunct Assistant Professor of Molecular Pharmacology, Physiology and Biotechnology

Brown Affiliations

research overview

Our research examines the mechanisms mediating contraction of the smooth muscle in the esophagus and Lower Esophageal Sphincter (LES). Disorders of esophageal motor function and LES competence, for instance gastroesophageal reflux disease, affect more than one in ten adults over 40 and one in four adults over 60 years of age. We investigate the inflammation-associated changes in the signaling mechanisms mediating esophageal contraction that occur with gastroesophageal reflux disease.

research statement

Disorders of esophageal motor function and competence of the Lower Esophageal Sphincter (LES), for instance gastroesophageal reflux disease, affect more than one in ten adults over 40 and one in four adults over 60 years of age.

Our research is focused on the mechanisms mediating contraction of the smooth muscle in the esophagus and LES, in normal conditions and during inflammation. We use human esophageal specimens from organ donors, when available, or the cat esophagus as a model for the human esophagus. We study signal transduction mediating contraction of circular muscle from the body of the esophagus and LES and the sequence of events responsible for the onset and development of inflammation and for alterations in esophageal and LES motor function.

We find that acid-induced esophageal inflammation begins with refluxed acid activating proton-sensitive vanilloid type 1 receptor or transient receptor potential vanilloid type 1 (TRPV1), present in the esophageal mucosa, resulting in production of the neurotransmitters substance P and calcitonin-gene-related peptide (CGRP) and of platelet activating factor (PAF). PAF diffuses to the muscle layer and induces the production of several inflammatory mediators including interleukin (IL)-6, IL-1, H2O2 (hydrogen peroxide), and more PAF by muscle cells. These inflammatory mediators reduce esophageal contraction by inhibiting release of acetlycholine (ACh) from cholinergic nerves.

These data suggest that esophagitis may begin from activation of TRPV1 receptors in esophageal mucosal epithelial cells, and that PAF may be an important factor contributing to alterations in motor function that are associated with gastroesophageal reflux disease.

funded research

Coinvestigator, National Institutes of Health (NIH) RO1-DK28614 "Biophysical Principles of Peristaltic Phenomena." Direct cost $242,000 per year, 8/1/03-6/30/07

Coinvestigator, NIH RO1-DK57030 "Inflammation and Signal Transduction in Esophagitis." Direct cost $175,097, 12/1/99 – 2/28/03.