Principal Investigators: Sourav Halder, PhD, Postdoctoral Scholar, Northwestern Medicine, Division of Gastroenterology and Hepatology, Northwestern Feinberg School of Medicine Wenjun Kou, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology) Every year, diagnoses are growing of eosinophilic esophagitis (EoE), a chronic, destructive allergic condition with many sub-types, that causes white blood cells (eosinophils) normally found elsewhere in the body to accumulate in the esophagus. Their presence causes inflammation, scarring, and stiffening of the esophagus. This damage impairs the ability of the esophagus to move foods and liquids from the throat to the stomach via esophageal muscle contractions—a process called peristalsis. Problems swallowing is the hallmark of EoE, which contributes to thousands of food impactions requiring urgent endoscopies each year. An innovative diagnostic tool recently developed by Northwestern gastroenterology investigators called FLIP Panometry has provided a novel method for diagnosing EoE through contraction patterns. This year’s DHF grant will support Dr. Halder’s team in their efforts to better define and classify the many different forms of the disease EoE. By harnessing the power of artificial intelligence to analyze FLIP data, the researchers hope to improve the current one-size-fits-all diagnostic approach by personalizing treatments to specific types of EoE and offering patients their best quality of...
Principal Investigator: Marie-Pier Tetreault, PhD, Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine A dangerous immune system condition that affects children and adults, eosinophilic esophagitis (EoE) occurs when allergic reactions inflame and scar the esophagus. The normally flexible esophagus, that connects the opening of the mouth down to the entry of the stomach, becomes stiff and unable to pass food and liquids down to the stomach. This leads to problems swallowing, heartburn, vomiting, pain, and malnutrition. Despite gains in treating EoE, many patients still have difficulties swallowing or they no longer respond to available therapies. A type of cell overgrowth called basal cell hyperplasia (BCH) has been blamed for progressive esophageal stiffening. While BCH is strongly linked to disease severity,little is known about the molecular and cellular changes that drive BCH. Uncovering the molecular underpinnings of EoE to develop more effective therapies, Dr. Marie-Pier Tetreault’s team recently published a study that points the finger at two genes: SOX2 and KLF5. The researchers hypothesize that the elevation of SOX2 and KLF5 expression correlates with disease outcomes after treatment. With funding from this year’s DHF award, the investigators intend to analyze already biobanked (from the DHF BioRepository) esophageal tissue samples from patients undergoing diverse therapies. The team will look to connect the dots between changes in biomarker expression, treatment responses, and clinical outcomes. Using cutting-edge imaging techniques and clinical assessments, the group hopes to better understand EoE to pave the way toward more personalized and targeted therapies for current and future patients. Better, more effective treatment can preserve remaining esophageal function and prevent further esophageal...
Principal Investigator: Joshua Wechsler, MD An allergic/immune condition, the inflammatory process of eosinophilic esophagitis (EoE) leads to chronic swallowing problems and food impaction. These symptoms develop when large numbers of white blood cells called eosinophils build up in the inner lining of the esophagus. EoE is on the rise in the United States, contributing to more than $1.4 billion in health care costs annually. Recently, EoE patients have been found to experience abrupt food-induced responses of the esophagus (FIRE). Symptoms occur immediately after the ingestion of foods that don’t typically trigger eosinophilic inflammation. Preliminary data from Dr. Ikuo Hirano of the Northwestern Medicine Digestive Health Center suggests these patients are sensitized to specific allergy-related antibodies directed at FIRE-associated foods. An antibody linked to food allergies, IgE typically involve mast cells—immune cells present within tissues such as the esophagus that are increased in patients with EoE. Dr. Wechsler’s study will examine esophageal biopsies to determine whether IgE is present on mast cells and whether increased IgE+ mast cells are increased in patients with FIRE when compared to those without FIRE...
Principal Investigator: Joshua Wechsler, MD Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus. Specific foods can trigger esophageal inflammation leading to pain, difficulty swallowing and malnutrition. Elimination diets remain a mainstay for identifying triggers since effective biomarkers or testing are currently nonexistent in this chronic disease. Previous work of Dr. Wechsler’s team revealed an immune response of white blood cells (T-cell receptors) in patients with active EoE who underwent rigorous dietary elimination and reintroduction regimens. Pursuing this promising line of research, Dr. Wechsler intends to examine esophageal biopsies for evidence of the specific immune response of white blood cells to specific foods. The investigators will use deep sequencing of the T-lymphocyte receptor to identify how frequently certain types of T-cells exist between adults with similar and unique food triggers. Findings from this study could open the door to building a digital library of T-cell receptors that identify specific foods and allow for more personalized...
Principal Investigator: Marie-Pier Tetreault, PhD Patients with eosinophilic esophagitis (EoE), a chronic immune/allergic condition affecting children and adults, develop difficulty swallowing food and food obstructions in the esophagus (food tube between the mouth and stomach). Dr. Tetreault’s team has created a new mouse model that more accurately replicates the disease process of EoE and exhibit all the features observed in patients with the disease. This game changing animal model offers a unique opportunity to better understand the molecular mechanisms driving EoE. By performing “single-cell RNA sequencing”, Dr. Tetreault hopes to determine how changes in specific molecules in epithelial cells control the development of eosinophilic esophagitis. The team will perform these studies in mice that currently have the disease as well as in mice that have yet to show any obvious signs or symptoms. Dr. Tetreault believes that the early-stage disease models will help identify the initiating molecular events that lead to EoE and provide insight into the development of earlier intervention strategies now lacking in the field of...
