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...

Tumor-Promoting Functions for Potential Therapies in Pancreatic Cancer

Principal Investigator: Beatriz Sosa-Pineda, PhD Pancreatic cancer has one of the worst survival rates in the world, and patients have very limited therapeutic options to fight the disease. It is predicted that close to 47,000 Americans will succumb to pancreatic ductal adenocarcinoma (PDAC) in 2020. Meeting the dire need for new therapies and diagnostic methods requires a better understanding of the fundamental biology of PDAC. Learning more about the molecular mechanisms that govern tumor formation, progression, and spread (metastasis) is critical to improving outcomes. In this study, Dr. Sosa-Pineda intends to build on her lab’s previous findings to firmly establish the role of a new gene regulator, the transcription factor ONECUT2, in the development of pancreatic cancer. This project will use molecular approaches to abolish the expression of ONECUT2 and test its effect on pancreatic tumor function. The Sosa-Pineda team will employ additional approaches to identify specific pathways and functions regulated by ONECUT2 in pancreatic...