THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigators: Amanda C. Cheung, MD, Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine Andres Duarte-Rojo, MD, PhD, Professor of Medicine (Gastroenterology and Hepatology) and Surgery (Organ Transplantation), Northwestern Medicine, Northwestern Feinberg School of Medicine A serious public health concern, excessive alcohol consumption causes almost 50% of liver disease deaths in the United States. Unfortunately, many patients with alcohol-associated liver (ALD) damage have late stage disease by the time they receive a diagnosis. A major liver transplant is often their only option for lifesaving treatment. Importantly, the relationship between amounts of alcohol consumed and damage to the liver is difficult to predict, with some patients (often women) developing liver scarring earlier with less alcohol consumption while others are able to drink more without significant health complications. To add to this challenge, no detection tests currently exist to identify early signs of liver scarring (fibrosis) in individuals with alcohol use disorder. This year, a DHF award is supporting Dr. Amanda Cheung’s team in identifying a biomarker for early fibrosis to improve ALD screening for at-risk individuals. A network of proteins and molecules surrounding cells, the extracellular matrix (ECM) may offer promise as an early warning system. Inflammation from ALD has been shown to damage the ECM, increasing detectable chemical changes, or “degradome,” that are precursors to developing irreversible fibrosis. Up to this point, limited studies have looked only at the degradome profiles in the blood of patients with liver fibrosis. In this new DHF study, Dr. Cheung’s team is investigating the degradome profiles of patients with ALD before...
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...
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...
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...
