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...
Principal Investigator: Sarah Taylor, MD, Assistant Professor of Pediatrics (Gastroenterology, Hepatology, and Nutrition), Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern Medicine, Feinberg School of Medicine Gestational alloimmune liver disease (GALD) is the leading cause of liver failure in newborns. This disease occurs when maternal antibodies injure the liver of the fetus during pregnancy. Infants with GALD require prompt diagnosis and treatment at birth. Even with treatment, about 50% of infants with GALD do not survive. Quickly obtaining a precise and reliable diagnosis remains challenging. DHF’s grant is enabling Dr. Taylor’s lab to create histologic scoring criteria that can be easily disseminated to enable prompt and reliable diagnosis of GALD. Evaluating the ribonucleic acid (RNA) of livers from affected patients, the Taylor team hopes to identify new blood tests that will differentiate GALD from other causes of neonatal liver failure. Dr. Taylor’s research is fostering a better understanding of GALD’s disease process to help launch future research and the development of life-saving therapies for newborns facing this potentially deadly...
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...
Principal Investigator: Alyssa Kriegermeier, MD Children with liver disease frequently suffer from jaundice caused by the poor flow of bile from the liver to the intestines—a disease state called cholestasis. Currently no treatments are available that effectively prevent liver failure due to pediatric cholestatic liver diseases. Lifesaving liver transplantation is often the only answer. Cells within the liver deal with the stress from cholestasis via stress-induced pathways known as the unfolded protein response (UPR). While the UPR has been studied in adult liver diseases, little is known about its activation in children. Dr. Kriegermeier previously demonstrated, in an animal model of primary sclerosing cholangitis (PSC), one form of cholestatic liver disease affecting children and adults (about 80 percent of whom also have inflammatory bowel disease (IBD- Crohn’s disease, ulcerative colitis, etc.)), that removing parts of the UPR affects disease progression. This study will seek to better understand the differences in adults and children within this cell stress response during times of cholestasis. Identifying new therapeutic targets will provide a springboard for developing treatments for these children that will hopefully prevent them from needing liver...
