Principal Investigator: Guang-Yu Yang, MD Chronic inflammation is an important risk factor for cancer. Patients with ulcerative colitis (UC) face a significantly increased risk of developing colorectal cancers. Damaged DNA and genetic alterations can be caused by the inflammatory process. Identifying crucial inflammation-associated molecular events offers potential targets to predict and prevent cancers. Missense p53 mutations are one of the most common and earliest molecular events seen in UC-associated carcinogenesis. Yet little is known about the evolution of p53 mutations during the long-term course of UC and whether targeting these mutations will have an impact on the long-term cancer risk in patients with UC. Employing a next-generation sequencing approach, Dr. Yang’s study aims to determine the mutation spectrum and load of the p53 gene in this patient population. The researchers intend to identify whether specific p53 mutations are critical in driving UC-induced carcinogenesis, and to evaluate its role as an efficient biomarker for predicting the risk of cancer development in UC...
Principal Investigator: Darren Brenner, MD Intestinal bacterial overgrowth (IBO) occurs when excessive amounts of bacteria build up in the small intestine (which is usually nearly sterile). These bacteria ferment ingested food, producing hydrogen, methane, and carbon dioxide. These intestinal gases can induce GI symptoms, including abdominal pain, bloating, distention, diarrhea, and constipation. Antibiotics often help, but for some patients, disruptive digestive symptoms will persist. IBO is subcategorized into two types: 1.) small intestinal bacterial overgrowth and 2.) intestinal methanogenic overgrowth. Recent studies suggest that increased methane production may come from the overgrowth of a specific type of bacteria. No current therapies exist to treat methane predominate IBO. An initial study of the herbal supplement Atrantil has shown promise. Investigating the potential benefit of this “holistic” treatment, Dr. Brenner will conduct a trial of Atrantil in 30 patients at the Northwestern Medicine Digestive Health Center. Researchers will evaluate Atrantil’s impact on reducing methane levels, lessening symptoms, and enhancing quality of life. The team believes Atrantil could offer an inexpensive and safe treatment for...
Principal Investigator: Josh Levitsky, MD | Co-Principal Investigator: Imran Nizamuddin, MD Primary sclerosing cholangitis (PSC) causes chronic inflammation of the bile ducts and, over time, potential liver failure. What triggers PSC and how it is strongly linked to ulcerative colitis (UC) remains unclear. One theory is that a “leaky gut” allows toxic compounds from the intestines to erroneously enter the liver. Dr. Levitsky’s team intends to test this theory by measuring intestinal permeability in PSC patients. Intestinal permeability (leakiness) can be studied by comparing absorption of different simple sugar solutions. Study participants will drink several sugar solutions to compare absorption and elimination in the urine. Researchers anticipate that the sugar levels in the urine will be different between patients with PSC, patients with PSC and ulcerative colitis, and healthy patients. If this occurs, the team will evaluate therapies, such as antibiotics, to assess their impact on the “leaky gut.” This project may serve as an initial step toward developing personalized treatment options for patients who currently don’t have any therapeutic options—currently a high unmet need in the field of...
Principal Investigator: Lisa B. VanWagner, MD Liver transplantation extends the lives of many patients with liver failure. Yet, one in three recipients will experience a heart disease event after liver transplant surgery due to the effects of immunosuppression causing a high prevalence of cardiovascular risk factors, such as high blood pressure (BP). Decreasing hypertension in these patients could help improve their outcomes. While there are different methods for detecting high BP, some are better than others. Home monitors and portable/wearable 24-hour monitoring devices often best reveal how blood pressure readings relate to daily activities and sleep and provide keener insights into patients’ true blood pressure levels than measurements taken in the clinic. Dr. VanWagner’s study will involve measuring blood pressure over time in 50 Northwestern liver transplant recipients. Her team will use the office, home, and 24-hour blood pressure measurement approaches to enable interventions to lower blood pressure and prevent dangerous heart disease events after transplant...
Principal Investigator: Marie-Pier Tétreault, PhD Scleroderma is considered an autoimmune disease (the immune system erroneously attacks the body) causing stiffening of the body’s connective tissues of numerous organs leading to stiffening and functional disruptions. More than 95 percent of scleroderma patients develop GI problems, with the esophagus being the most commonly affected organ. Weakening muscle tissue and impairing function, scleroderma esophageal disease can result in complications such as gastroesophageal reflux (GERD), Barrett’s esophagus, and/or adenocarcinoma. Despite efforts to better understand the nature of scleroderma in multiple organs, how scleroderma damages the esophagus remains unclear. Consequently, no treatment exists to change the course of scleroderma esophageal disease. Determining the molecular mechanisms underlying the disease process is critical to developing effective therapies. Using a powerful new technology called single-cell RNA sequencing (scRNA-seq), Dr. Tétreault will examine esophageal biopsies from patients with scleroderma esophageal disease. By pinpointing specific molecular changes in this patient population compared to those of healthy patients, her team hopes to identify novel targets for diagnosis and treatment of this complex...
