Exposing and Confronting Destructive Chronic Inflammation in Acid Reflux (GERD)

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...

Molecular Changes in Scleroderma Esophageal Disease

Principal Investigator: Marie-Pier Tétreault, PhD Scleroderma is considered an autoimmune disease (the immune system erroneously attacks the body) causing stiffening of the body’s connective tissues of numerous organs leading to stiffening and functional disruptions. More than 95 percent of scleroderma patients develop GI problems, with the esophagus being the most commonly affected organ. Weakening muscle tissue and impairing function, scleroderma esophageal disease can result in complications such as gastroesophageal reflux (GERD), Barrett’s esophagus, and/or adenocarcinoma. Despite efforts to better understand the nature of scleroderma in multiple organs, how scleroderma damages the esophagus remains unclear. Consequently, no treatment exists to change the course of scleroderma esophageal disease. Determining the molecular mechanisms underlying the disease process is critical to developing effective therapies. Using a powerful new technology called single-cell RNA sequencing (scRNA-seq), Dr. Tétreault will examine esophageal biopsies from patients with scleroderma esophageal disease. By pinpointing specific molecular changes in this patient population compared to those of healthy patients, her team hopes to identify novel targets for diagnosis and treatment of this complex...

Which molecular changes are causing the development of eosinophilic esophagitis?

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...

How Does Inflammation Affect the Development and Progression of Eosinophilic Esophagitis?

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...
DHF BioRepository

DHF BioRepository

Introducing a groundbreaking research technology, the The Digestive Health Foundation became a founding supporter in 2017 of a powerful new resource for digestive health medical research: The Digestive Health Foundation BioRepository.  As one of only a few GI biorepositories of its kind in the world, the DHF BioRepository stores, organizes, and makes accessible (digitally, in real time) blood and tissue samples from patients and family members diagnosed with one or more of the digestive disorders treated at the Northwestern Medicine Digestive Health Center.  Digestive disease research using the DHF BioRepository will leverage the latest advances in information technology with cutting-edge biologic and molecular research techniques to better understand gastrointestinal diseases and to help develop better treatment options for patients. Across GI sub-specialties, from liver and pancreatic cancers, esophageal diseases/swallowing disorders, inflammatory bowel disease (Crohn’s Disease and ulcerative colitis), GERD, IBS, bariatric surgery, nutritional issues, and many more, the extensive and growing patient network at Northwestern Medicine provides a diverse and valuable resource of participants.  After a patient chooses to participate, Northwestern Medicine directly links the patient’s anonymized electronic medical record, physiologic diagnostic test results, imaging results, and patient-directed quality of life indicators to a tissue bank that will include: samples obtained during endoscopy (biopsies), blood, urine, and stool.  The DHF BioRepository’s depth of capacity will enable physician scientists around the world to pursue large scale research studies into the mechanisms of digestive diseases.  Discoveries about the natural history and progression of digestive disease is providing the insight necessary to develop new diagnostic tools, better treatments, and eventual cures for digestive disease patients and future generations. — The Digestive Health...