Principal Investigator: Guang-Yu Yang, MD, PhD Most patients with Eosinophilic Esophagitis (EoE) experience an abnormal immune-mediated response to food antigens. Identifying unique biomarkers involved in the pathogenesis of allergic inflammation could significantly improve treatments. The conversion of cell membrane arachidonic acid to ω-6 prostaglandin and ω-6 leukotriene eicosanoids during the inflammatory cascade provides many potential drug targets to impede the inflammatory process in patients with EoE. ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) have opposing influences on inflammation. Currently, there is no study on PUFA metabolism and the role these PUFAs metabolites play in the pathogenesis of EoE. Dr. Yang’s study aims to determine the ω-3 and ω-6 PUFAs metabolites/eicosanoids profile in eosinophilic esophagitis using a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based metabolomics approach and to identify the unique eicosanoids or biomarker/s for diagnosis, prognosis and monitoring the therapeutic effect on...
Principal Investigator: Marie-Pier Tétreault, PhD The epithelial lining of the esophagus serves as the first line of defense to protect the underlying tissue from various external insults. Upon injury and inflammation, a rapid and efficient restoration of the esophageal epithelial barrier is needed. Failure to restore this barrier ultimately leads to pathological consequences. To date, most studies of inflammation have focused in immune cells because they are the paradigmatic inflammatory cell type. Yet immune cells are not the only cell type involved in inflammation and immunity. Epithelial cells sense and initiate inflammation, and also play a key role in the production of inflammatory molecules. It still remains unclear, though, how epithelial cells contribute to inflammation in patients with Eosinophilic Esophagitis (EoE). The investigators will determine how epithelial cells control inflammation and fibrosis in eosinophilic esophagitis. The Tétreault laboratory will also test how blocking mediators of inflammation can prevent the development and progression of...
In Eosinophilic Esophagitis (EoE), a variety of foods trigger inflammation in the esophagus. Diet elimination remains a mainstay treatment approach, with the number and type of food triggers varying between patients. Some respond well to eliminating a single food while others require the removal of multiple foods. Although no biomarkers or testing currently exist to help pinpoint specific triggers, previous studies have found a key role for white blood cells known as T-cells. This study will assess the novel association between individual food triggers and T-cell clonality. Dr. Wechsler and his team intend to examine esophageal biopsies for evidence of the specificity of immune response of white blood cells to specific foods. The researchers will use deep sequencing of the T-lymphocyte receptor to identify how frequently unique types of T-cells appear. The team hopes this data will help explain how the immune system “learns” to respond to specific foods and, ultimately, provide a potential...
Principal Investigator: Richard M. Green, MD A chronic bile duct and liver disease, Primary Sclerosing Cholangitis (PSC) affects more than 50,000 Americans and can progress to cirrhosis, liver failure, and bile duct cancer. Currently, the only effective therapy is liver transplantation. Better understanding the pathogenesis of PSC is urgently needed to develop new therapies. In recent cell culture and animal studies, Dr. Green and his colleagues focused on a protective cell signaling pathway: the unfolded protein response (UPR). They found that the UPR is activated when bile flow is impaired, and mice lacking UPR genes in their liver are highly susceptible to injury from bile duct obstruction. Now moving forward with the first human investigations examining UPR, Dr. Green aims to determine how it is activated in the bile ducts of patients with PSC. The team plans to study bile duct tissues obtained during endoscopic procedures performed for bile duct obstruction. The identification of “protective” genes and proteins could lead to new drug targets and, ultimately, the development of novel medical...
Principal Investigator: Shilajit D. Kundu, MD One million-plus Americans have IBD, accounting for more than two million ambulatory and emergency room visits annually. This health care utilization can lead to annual medical expenditures ranging from $5,000 to $8,000 per patient. Reducing unnecessary medical costs in this patient group is paramount. Take for example, PSA tests. While PSA screening can reduce prostate cancer deaths, false-positive elevations commonly occur, especially for patients with IBD. The Kundu research group recently found that men 65 and older with IBD, who underwent prostate cancer screening at Northwestern Memorial Hospital, had higher PSA values than non-IBD controls. In addition, men with IBD had a significantly higher risk of prostate cancer. However, whether the elevation in PSA is due to IBD-related inflammation versus a true reflection of an increased risk of prostate cancer remains unclear. Study findings may optimize how men with IBD are screened for prostate cancer by better assessing their risk while at the same time reducing needless medical...
