Principal Investigator: Mohammad Ali Abbass, MD, Assistant Professor of Surgery (Gastrointestinal), Northwestern University Feinberg School of Medicine Colorectal cancer is the second most common cause of cancer-related death in the United States, but it is also largely preventable with screening. The Abbass team is identifying a genetic tool based on blood samples that can accurately predict an individual’s lifetime risk for developing colorectal cancer. The researchers will use DNA extracted from blood specimens of Northwestern Medicine patients who have either been diagnosed or confirmed clear of colorectal cancer. They will then evaluate changes that occur in the DNA building blocks to validate a polygenic risk score established for European patients. The aim is to use this score to identify patients who lack a family history for colorectal cancer but who should potentially begin their colorectal cancer screening before age 45, the age currently recommended to begin screening. The project could lead to a larger scale study that would target a more expansive population to initiate earlier screening in selected patients and decrease colorectal cancer-related deaths in younger patients. As a result, many people could more accurately know their individual genetic risk, pursue earlier screening if indicated, and detect colorectal cancer earlier, improving their chances of...
Principal Investigator: Fred W. Turek, PhD, Charles and Emma Morrison Professor, Northwestern Weinberg College of Arts and Sciences Experiments in animal models of Inflammatory Bowel Disease (IBD) have shown that disruption of sleep and circadian rhythms increases susceptibility to intestinal inflammation. In addition, studies in patients with IBD have found alterations in the circadian clock that may indicate pervasive sleep problems. Despite these connections, little is known about how sleep and circadian rhythms are involved in gut health, or if strategies to promote sleep and reduce stress can mitigate the risk for intestinal inflammation. Alterations in the intestinal bacteria (microbiome) and abnormal host responses to these bacteria may be contributing factors to the development of IBD. Recent studies have revealed links between the microbiome, circadian rhythms, and the sleep-wake cycle. In previous work, Dr. Turek’s team found that a probiotic promoted resilience to sleep restriction and acute stress exposure. In this project, the investigators are determining if a probiotic can also protect against intestinal inflammation and pathology in a mouse model of colitis. The potential for probiotics to improve sleep and decrease disease activity is an exciting avenue of study that may provide low risk options to improve the daily lives of IBD...
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...
