THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigator: Xiaoying Liu, PhD, Research Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine A rare liver disorder, primary sclerosing cholangitis (PSC) occurs when thickening of bile ducts block the normal, necessary flow of bile within the digestive system. Buildup of toxic bile acids can lead to irreversible liver cirrhosis, cancer, and the need for a risky, life-altering liver transplant. For unknown reasons, up to 70% of patients with PSC also have inflammatory bowel disease (IBD), especially ulcerative colitis. Today, effective treatments don’t yet exist to prevent this progressive and potentially fatal liver disease. Dr. Xiaoying Liu’s team is using this year’s DHF grant award to better understand the disease process of PSC in order to stop it from damaging the liver. The researchers are studying a molecular pathway called “unfolded protein response (UPR)” that springs into action to protect cells from toxicity in the liver. This exciting study stands on the shoulders of previously successful DHF funded research proving increased UPR pathway gene expression in post-liver transplant patients. Dr. Liu hopes to further delineate the protective role of UPR to create a first-in-the-world liver cell atlas in PSC to map cell signaling and cellular interactions. These studies offer important promise for identifying molecular targets to develop much needed new drug therapies for PSC...
THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigator: David Escobar, MD, PhD, Assistant Professor of Pathology (Gastrointestinal Pathology), Northwestern Medicine, Northwestern Feinberg School of Medicine The second leading cause of death in the U.S., colorectal cancer diagnoses have skyrocketed in recent years, especially in younger people in their 30s and 40s, for reasons that are still under investigation. In 2023 over 153,000 Americans will be diagnosed with colorectal cancer, with 30% of those diagnoses being rectal cancer. During the past 20 years, treatment for locally advanced rectal cancer has evolved from traditional chemotherapy, radiation and surgery, and then more chemotherapy, to a new standard of care known as total neoadjuvant chemoradiotherapy (TNT). This more personalized medicine strategy initially involves only chemotherapy and radiation. Many patients undergoing TNT do not need surgery—preserving crucial organs and normal function, as well as maintaining quality of life. Dr. David Escobar speculates that the radiation used in TNT uniquely sensitizes the tumors of these patients, leading to higher cancer cure rates without surgery in contrast to less successful, risker traditional therapy. This year’s grant from DHF will advance his team’s work investigating how radiation therapy may change the genetics of patients’ tumor cells by making the cells more responsive to cancer killing strategies like TNT. If this hypothesis proves to be true, further research could be launched, on strategies like immunotherapy, to help patients who still have residual cancer after TNT in avoiding colorectal surgery and the often serious, life-changing complications that come with...
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...
