Principal Investigator: Josh Levitsky, MD, Professor of Medicine (Gastroenterology and Hepatology), Medical Education and Surgery (Organ Transplantation), Northwestern University Feinberg School of Medicine Autoimmune hepatitis (AIH) occurs when the body’s immune system attacks its own liver cells, causing long term scarring and damage to the liver. No one knows precisely what causes autoimmune hepatitis (AIH), but it is diagnosed more frequently in patients with other autoimmune diseases (e.g., celiac disease, ulcerative colitis, rheumatoid arthritis, etc.) and in women, and often begins in adolescence or young adulthood. Standard treatment focuses on suppressing the immune system with medications, yet immunosuppressants have many potentially harmful side effects. General recommendations call for patients to stop taking the medications when they are no longer needed. Unfortunately, without them, most patients soon relapse and risk more liver injury. Currently, tracking relapses requires taking a biopsy of the liver—a very invasive procedure—and looking at it under the microscope. The Levisky lab believes that measuring levels of biomarkers in the blood may offer a less invasive window into the liver than a traditional biopsy, giving physicians the ability to predict AIH relapse before the liver incurs any damage. This project offers the potential for better monitoring of patients with AIH. It also may shape the future of personalized treatments to individualize immunosuppressant therapy by using simple, cost effective blood draws rather than riskier liver...
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...
Principal Investigator: Wenjun Kou, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Feinberg School of Medicine Many serious esophageal motility disorders and diseases are diagnosed with the newer technology of High-Resolution Impedance Manometry (HRIM). HRIM measures pressures and fluid movement in the esophagus and lower esophageal sphincter connecting to the stomach. Dr. Kou’s team is transforming an HRIM-based analysis technique into new tools with metrics/outcomes for use by physicians in clinical practice. Taking HRIM analytics a step further offers more specific evaluation of esophageal function. The esophageal metrics being studied include bolus retention; intrabolus pressure (IBP) and distensibility of the esophageal body at each phase; pressure and distensibility of esophagogastric junction (EGJ) as well as emptying flow rate. Dr. Kou’s research study involves: 1) designing and implementing metrics-based algorithms to analyze esophageal function; and 2) deriving a metrics dataset from HRIM studies of various tissue/cellular phenotypes. The research team will then use complex statistical analysis and the new field of ‘machine learning’ to evaluate the discriminating power (usefulness) of the metrics, and derive classification models of esophageal function for use in diagnosing esophageal diseases. Dr. Kou will conduct a further comparison of those results with similar outcomes from panometry—another recently developed technology used in esophageal evaluations. Using these high-level tools to develop precise metrics and advanced classifications in esophageal diseases ultimately improves physicians’ ability to diagnose and treat esophageal diseases as accurately and quickly as possible, minimizing the long-term effects of these potentially debilitating and life-threatening...
Principal Investigator: Ronen Sumagin, PhD, Assistant Professor of Pathology (Experimental Pathology), Northwestern Feinberg School of Medicine When conventional medications, such as corticosteroids or 5-aminosalicylates, fail to work in IBD patients, biologics that block a critical inflammatory molecule called tumor-necrosis-factor alpha (TNFα) are commonly prescribed. However, one third of patients receive no relief from these biologic drugs, and other patients become resistant to the therapy over time, forcing physicians to pursue other avenues of treatment for their patients. In previous work, the Sumagin lab and other researchers established the important role of immune cells, called neutrophils, in IBD. Recent studies revealed that in inflamed tissue there are diverse neutrophil populations with distinct functions. With the DHF grant, Dr. Sumagin is using innovative single-cell sequencing to map neutrophil diversity in IBD. His research team seeks to determine whether specific neutrophil subtype(s) dictate resistance to anti-TNFα therapy. This effort offers great promise for unraveling new disease processes and identifying predictive biomarkers of treatment outcomes or drug targets to prevent anti-TNFα resistance in IBD patients. Physicians could then predict ahead of time which drugs may work for their patients living with IBD. This valuable insight could potentially decrease symptom or disease flares, as a result of drug inefficacy or resistance, in the long-term treatment of...
