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...

Personalized Exercise Program Improves Survival Rate in Liver Transplant Patients

Principal Investigator: Daniela P. Ladner, MD, MPH, Interim Director, Comprehensive Transplant Center; Professor of Surgery (Organ Transplantation) and Medical Social Sciences, Northwestern University Feinberg School of Medicine Patients with poor physical conditioning who are diagnosed with cirrhosis frequently experience worse outcomes before and after receiving a liver transplant. Exercise helps reduce frailty and leads to better outcomes, but patients face a variety of financial and logistical barriers to the regular physical activity needed to maintain strength. Additionally, transplant teams often expect patients to optimize their physical health on their own with little guidance. The Ladner research team seeks to optimize patient outcomes through a practical and affordable approach to enhance physical conditioning in the pre- and post-liver transplant setting. The researchers are developing a simple and cost-effective intervention called LIFT (Liver FrailTY), which will include a full in-person strength assessment, an exercise program with smart phone guidance, and remote coaching. Regular and frequent check-ins will be essential to encouraging patients to achieve recommended levels of exercise. Dr. Ladner’s study will then measure the impact of LIFT on strength as well as on positive clinical outcomes, such as increased survival and fewer hospitalizations for patients facing liver...

Unprecedented Use of DNA Modeling to Identify Lifetime Risk for Colon Cancer

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...

Can Probiotics Improve Circadian Sleep Rhythms and Symptoms in Ulcerative Colitis Patients?

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...

Predicting Relapse in Liver Failure (Autoimmune Hepatitis) Patients for Personalized Treatment

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...