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...
THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigator: Marie-Pier Tétreault, PhD, Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine Gastroesophageal reflux disease (GERD) affects up to 27% of the adult U.S. population, resulting in more than seven million patient visits annually. Over time, GERD leads to serious complications such as erosive esophagitis, Barrett’s esophagus and esophageal cancers. However, how GERD functions at the molecular level is unclear, making it difficult to develop better treatments for patients living with this condition. This year, DHF is supporting Dr. Marie-Pier Tétreault’s work in identifying the molecular mechanisms that drive the development and progression of GERD, in the hopes of changing the future for patients living with this destructive esophageal condition. DHF funding will enable researchers to utilize state-of-the-art, single-cell RNA technology to rapidly look at the precise gene expression patterns of tens of thousands of cells in hopes of uncovering and identifying rare populations of diseased cells. Previous successful DHF funding of the Tétreault team uncovered valuable new insights and created new technology in profiling the unique cells involved in eosinophilic esophagitis (EoE) and scleroderma esophageal disease. This year, the research team is focusing on the widespread disease of GERD with a focus on new, critical treatment options for patients to decrease the risks of major esophageal complications, including...
Principal Investigator: Marie-Pier Tétreault, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern University Feinberg School of Medicine Gastroesophageal reflux disease (GERD/acid reflux) affects over ¼ (up to 27 percent) of U.S. adults, resulting in more than 7 million patient visits annually. GERD leads to complications such as erosive esophagitis, Barrett’s esophagus and esophageal cancer. Learning more about the molecular basis for the development and progression of GERD is critical to improving treatment options and decreasing the risks for these esophageal conditions. Dr. Tetreault is looking at the role of the crucial mediator of inflammation IKKβ in the development of chronic GERD. The team will use molecular approaches to shut down the expression of IKKβ and evaluate the impact of this loss on the development of GERD. This project will also employ a new technology called single-cell RNA sequencing (scRNA-seq) that enables the rapid determination of the precise gene expression patterns of tens of thousands of individual cells. Employing scRNA-seq should help give greater insight into how IKKβ signaling impacts the regulation of the inflammatory process in chronic gastroesophageal reflux. Interrupting the disease process of GERD can crucially impact long term patient prognosis and risk of...
Principal Investigator: Joshua Wechsler, MD, MS, Attending Physician, Gastroenterology, Hepatology and Nutrition; CURED (Campaign Urging Research for Eosinophilic Disease) Foundation Research Scholar, Assistant Professor of Pediatrics (Gastroenterology, Hepatology, and Nutrition) and Medicine (Allergy and Immunology), Northwestern University Feinberg School of Medicine Eosinophilic Esophagitis (EoE) is a chronic immune disorder of the esophagus caused by certain foods triggering an allergic response, or by chronic GERD (Gastroesophageal reflux disease/acid reflux). Over time, chronic inflammation from EoE can lead to fibrosis (scarring) and subsequent esophageal stiffness and narrowing of the esophagus. Patients experience difficulty passing food and impaction when food becomes trapped in the esophagus. Identifying early signs and drivers of scarring would help prevent the development of these and other serious complications. Endoscopic Functional Luminal Impedance Probe (EndoFLIP) is used to measure esophageal distensibility (stiffness or stretchiness). Prior research has demonstrated that eosinophils—a type of immune cell—have a weak association with esophageal distensibility. While different types of immune cells play a role in EoE, the association of non-eosinophil immune cells has never been studied. Dr. Wechsler is examining the correlation between esophageal distensibility and non-eosinophil immune cell populations in children with EoE. The team expects this work will guide future studies on EndoFLIP, as well as how immune cells, such as mast cells and T-cells, impact esophageal fibrosis to help develop targeted treatments for EoE that can inhibit disease progression and its destructive effects on pediatric...
