New Genetic Risk Factor (CLDN2) Found Responsible for Increased Susceptibility to Pancreatitis

Principal Investigator: Beatriz Sosa-Pineda, PhD, Professor of Medicine (Nephrology and Hypertension), Northwestern University Feinberg School of Medicine Pancreatitis is a dangerous inflammatory condition, often associated with considerable socioeconomic risk factors. Usually diagnosed in middle-aged to elderly individuals, and more commonly in men versus women, pancreatitis is responsible for the majority of gastrointestinal disease-related hospital admissions. Although acute to chronic pancreatitis susceptibility results from a combination of genetic, metabolic, and environmental factors, it remains challenging to predict the onset, progression, and severity of the disease. Understanding how distinct genetic risk factors affect the pathologic outcome in pancreatitis is key to developing better diagnostic and therapeutic tools for physicians treating patients. The Sosa-Pineda team is beginning to dissect the role of claudin-2 (CLDN2), a newly identified pancreatitis risk factor, in pancreatic ductal cell function and pancreatitis outcome. The investigators will use an animal model for these new studies that will complement previous results from Dr. Sosa-Pineda’s lab using CLDN2 knockout mice and pancreatic ductal cell cultures. The investigators expect to demonstrate that sustained expression of this gene exacerbates tissue injury, such as inflammation and fibrosis in chronic pancreatitis.  Illuminating a genetic pathway of this disease will enable further research to provide better, earlier diagnosis and targeted therapies for pancreatitis patients, allowing for better health...

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...

Division of Gastroenterology and Hepatology Northwestern Medicine/Feinberg School of Medicine
Center for Artificial Intelligence and Mathematics in Gastroenterology

Division of Gastroenterology and Hepatology Northwestern Medicine/Feinberg School of Medicine Center for Artificial Intelligence and Mathematics in Gastroenterology The Center for Artificial Intelligence and Mathematics in Gastroenterology (AIM-GI) is a first of its kind program developed in a division of Gastroenterology.  Artificial Intelligence and Machine Learning have the potential to vastly improve our ability to accurately predict, diagnose and treat our patients living with digestive diseases.  Through collaboration with engineers at the McCormick School of Engineering and physician scientists at the Feinberg School of Medicine at Northwestern University, our team has been incorporating mathematical modeling and advanced programming to study the mechanisms that lead to poor gastrointestinal function.  This work led to the development of a more formalized center that focuses on three main initiatives. Development of virtual organs which can be used to study the effects of surgery and medications; Development of new hybrid diagnostic tools using AI and machine learning to enhance diagnosis; Using machine learning and neutral networks to predict disease outcome. Although this is a new program, we have already had success developing an NIH funded Center of Research Expertise (CORE) and we have also developed new AI prototypes that can improve diagnostic accuracy and reliability of motility tests.  This work is supported by the generosity of the Digestive Health Foundation and these funds help provide the computational power and expertise required to continue to develop these innovative tools.  Our goal is to continue invent and develop new approaches and our partnership with the Digestive Disease Foundation will continue to allow us to grow and evolve this...

Predicting Symptom Improvement after Novel Endoscopic Treatment for Gastroparesis

Principal Investigator: Aziz Aadam, MD Gastroparesis is a debilitating condition that can cause persistent nausea, vomiting, and abdominal pain due to delayed stomach (gastric) emptying. The inability to eat or drink can lead to malnutrition and reduced quality of life. Current treatments are limited in both effectiveness and durability. A minimally invasive endoscopic procedure called G-POEM has recently shown promise in improving spasms of the sphincter muscle that prevent proper gastric emptying. G-POEM involves cutting this smooth band of muscle—that connects the stomach to the small intestine—to prevent further spasms and to allow the stomach to empty. Dr. Cai hopes to identify which gastroparesis patients would most likely benefit from this treatment using two novel methods: EndoFLIP, a probe that measures sphincter flexibility and antroduodenal manometry (ADM), a catheter that measures pressures throughout the upper gastrointestinal tract. Her team will look for specific EndoFLIP and ADM metrics that can be used to more effectively select patients for and predict improvement after...

Atrantil Supplement for Methane Predominate Intestinal Bacterial Overgrowth

Principal Investigator: Darren Brenner, MD Intestinal bacterial overgrowth (IBO) occurs when excessive amounts of bacteria build up in the small intestine (which is usually nearly sterile). These bacteria ferment ingested food, producing hydrogen, methane, and carbon dioxide. These intestinal gases can induce GI symptoms, including abdominal pain, bloating, distention, diarrhea, and constipation. Antibiotics often help, but for some patients, disruptive digestive symptoms will persist. IBO is subcategorized into two types: 1.) small intestinal bacterial overgrowth and 2.) intestinal methanogenic overgrowth. Recent studies suggest that increased methane production may come from the overgrowth of a specific type of bacteria. No current therapies exist to treat methane predominate IBO. An initial study of the herbal supplement Atrantil has shown promise. Investigating the potential benefit of this “holistic” treatment, Dr. Brenner will conduct a trial of Atrantil in 30 patients at the Northwestern Medicine Digestive Health Center. Researchers will evaluate Atrantil’s impact on reducing methane levels, lessening symptoms, and enhancing quality of life. The team believes Atrantil could offer an inexpensive and safe treatment for...