Principal Investigator: Marie-Pier Tétreault, PhD The epithelial lining of the esophagus serves as the first line of defense to protect the underlying tissue from various external insults. Upon injury and inflammation, a rapid and efficient restoration of the esophageal epithelial barrier is needed. Failure to restore this barrier ultimately leads to pathological consequences. To date, most studies of inflammation have focused in immune cells because they are the paradigmatic inflammatory cell type. Yet immune cells are not the only cell type involved in inflammation and immunity. Epithelial cells sense and initiate inflammation, and also play a key role in the production of inflammatory molecules. It still remains unclear, though, how epithelial cells contribute to inflammation in patients with Eosinophilic Esophagitis (EoE). The investigators will determine how epithelial cells control inflammation and fibrosis in eosinophilic esophagitis. The Tétreault laboratory will also test how blocking mediators of inflammation can prevent the development and progression of...
Principal Investigator: Guang-Yu Yang, MD, PhD Most patients with Eosinophilic Esophagitis (EoE) experience an abnormal immune-mediated response to food antigens. Identifying unique biomarkers involved in the pathogenesis of allergic inflammation could significantly improve treatments. The conversion of cell membrane arachidonic acid to ω-6 prostaglandin and ω-6 leukotriene eicosanoids during the inflammatory cascade provides many potential drug targets to impede the inflammatory process in patients with EoE. ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) have opposing influences on inflammation. Currently, there is no study on PUFA metabolism and the role these PUFAs metabolites play in the pathogenesis of EoE. Dr. Yang’s study aims to determine the ω-3 and ω-6 PUFAs metabolites/eicosanoids profile in eosinophilic esophagitis using a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics approach and to identify the unique eicosanoids or biomarker/s for diagnosis, prognosis and monitoring the therapeutic effect on...
Principal Investigator: Dustin Carlson, MD; Co-Principal Investigator: Erica Donnan, MD In 2017, more than 191 million opioid prescriptions were dispensed in the United States. Opioids frequently cause many gastrointestinal side effects such as bloating, reflux and constipation, yet not much is known about how opioids affect the esophagus and swallowing. Opioids can lead to symptoms that mimic esophageal disorders such as achalasia that could result in unnecessary invasive procedures including surgery. The largest study of its kind, this project will look into how opioids affect esophageal motility. Using the Esophageal Center of Northwestern’s motility registry, Drs. Carlson and Donnan have access to some 4,000 patients who have undergone high-resolution manometries to assess esophageal function. The team will look at patients who have had motility studies at Northwestern while on opioids and evaluate volunteer patients on opioids without swallowing symptoms. Given the widespread use of opioids, patients with opioid- induced swallowing problems will become more common. This study is essential in determining how opioids affect the esophagus so that clinicians can correctly evaluate and treat these...
In Eosinophilic Esophagitis (EoE), a variety of foods trigger inflammation in the esophagus. Diet elimination remains a mainstay treatment approach, with the number and type of food triggers varying between patients. Some respond well to eliminating a single food while others require the removal of multiple foods. Although no biomarkers or testing currently exist to help pinpoint specific triggers, previous studies have found a key role for white blood cells known as T-cells. This study will assess the novel association between individual food triggers and T-cell clonality. Dr. Wechsler and his team intend to examine esophageal biopsies for evidence of the specificity of immune response of white blood cells to specific foods. The researchers will use deep sequencing of the T-lymphocyte receptor to identify how frequently unique types of T-cells appear. The team hopes this data will help explain how the immune system “learns” to respond to specific foods and, ultimately, provide a potential...
Principal Investigator: Ronak Vashi Patel, MD Imagine a piece of food becomes stuck in your throat while eating dinner. Unfortunately, for many patients with Eosinophilic Esophagitis (EoE), this is a symptom that occurs all too often. Dysphagia, or difficulty swallowing, is a gastroenterology “red flag” that often alerts physicians to initiate a work up to determine the cause. Typically, the first step calls for an upper endoscopy to visually assess inflammation and narrowing (strictures) that can be treated. Prior data suggests that visual evaluation is not perfect. Missed strictures can lead to additional testing and delay diagnosis. Other tools have become available to assist in measuring the esophageal diameter such as the Functional Lumen Imaging Probe (FLIP), a novel technology. Dr. Patel’s research project aims to determine how accurately physicians measure esophageal diameter as compared to FLIP in patients with EoE. Better understanding the accuracy of endoscopic assessment by both visual estimation and FLIP assessment will offer insight into which tools should be used in diagnostic and therapeutic treatment of esophageal...
