Normally immune cells like polymorphonuclear neutrophils (PMNs) protect our body against invading pathogens, but sometimes they go overboard. Accumulating in tissue they can cause cell injury in the GI tract, leading to the development of Inflammatory Bowel Diseases (IBD) and potentially, colorectal cancer. While neutrophils can drive inflammation, it remains unclear just how they contribute to tumor development. Supported by funding from a Digestive Health Foundation, Ronen Sumagin, PhD, a faculty member in the Department of Pathology at Northwestern Medicine and colleagues plan to define the mechanism that allows neutrophils to both promote abnormal cell mutations and inhibit DNA repair genes. They will also study if neutralizing these harmful effects can prevent increased mutations and cancer. The research team will specifically explore the potential use of targeted inhibition PMN-derived miRNAs as an antitumor therapy and test the theory that PMNs play a critical role in causing genomic instability, cellular transformation and tumor growth. Recurring PMN-mediated injury to the intestinal lining is a hallmark of IBD and significantly enhances the risk of developing colorectal cancer (CRC). Current IBD therapies include steroids, which have harsh long-term side effects. Confirmation of the role of PMNs, and identification of specific targets to inhibit PMN activity in patients with IBD, could help reduce the need for steroids and lead to the development of future diagnostics for colon cancer. Preventative treatment in this vulnerable patient population—many of them young adults—could significantly reduce their risk of colon cancer, which typically increases with age. Beyond IBD patients, Dr. Sumagin’s groundbreaking discovery of the relationship between inflammation and cancer could have far-reaching implications for all inflammatory-related cancers, from...
Principal Investigator: Madeline McGuire Bertha, MD, MS Medical marijuana use has grown among patients attempting to tamp down the debilitating effects of Inflammatory Bowel Disease (IBD). However, no one knows if cannabis improves intestinal inflammation—critical to treating IBD. In fact, marijuana could be simply masking symptoms and delaying necessary medical treatment. To determine if that’s the case, Northwestern Medicine researchers led by internal medicine resident Madeline McGuire Bertha, MD, MS, will compare patients in symptomatic remission (feeling well/ without symptoms) who use marijuana to those in symptomatic remission who do not use it. The researchers suspect that while patients using cannabis feel fine, they actually may have a higher level of dangerous, underlying inflammatory activity than their perceived “lack of intestinal distress” might imply. Supported by a grant from the Digestive Health Foundation, the investigators will use blood and fecal tests to assess levels of intestinal inflammation in the two groups. In particular, they will focus on measuring a blood marker of inflammation, C-Reactive Protein, and a stool marker, fecal calprotectin. If the study hypothesis holds true, the IBD patients using marijuana as a proposed alternative or complementary therapy will be found to have significantly higher levels of these inflammatory markers compared to non-cannabis users who experience no symptoms. Findings of this study will help to advance the limited data assessing the therapeutic efficacy of cannabis on objective markers of intestinal inflammation in patients with IBD. These research efforts could have important clinical and societal implications as medical marijuana becomes more widespread. New knowledge in this area could help both ordering physicians and patients to make more informed...
Barrett’s Esophagus (BE) occurs when damaging acid reflux causes the lining of the esophagus to change from normal to pre-cancerous tissue. Although BE can be effectively treated with acid-blocking medications, some patients with more advanced disease often require endoscopic therapy to remove the abnormal tissue. While many experience successful outcomes with this treatment option, some 5 to 25 percent will redevelop the disease; recurrence puts patients at increasing high risk for esophageal cancer or adenocarcinoma. With a five-year survival rate of about 20 percent, this deadly cancer has increased by a factor of more than seven in the past 40 years. Many risk factors contribute to BE, including gender, with men are at higher risk than women; chronic heartburn and acid reflux, especially before age 30; and smoking. Interesting, the disorder has developed with increasing frequency in non-smoking young men between the ages of 20 to 45. Sri Komanduri, MD, Director of Interventional Endoscopy at Northwestern Medicine and his research team previously found that persistent acid reflux in patients who have undergone endoscopic therapy likely causes recurrent BE. Currently, these patients must undergo placement of an uncomfortable transnasal catheter over a 24-hour period to assess and measure persistent acid reflux. This testing helps gastroenterology specialists to determine the best treatment options: a combination of medications and endoscopic treatment or perhaps a referral for surgery. Due to costs and patient intolerance, though, this type of reflux testing has proven to be impractical. Studies of patients without endoscopically-treated BE have suggested consistent changes in the lining of esophageal biopsy samples, which strongly indicate uncontrolled acid reflux. Extrapolating from this observation, Dr....
Principal Investigator: Nirmala Gonsalves, MD Previously thought to be a rare disorder, Eosinophilic Esophagitis (EoE) has emerged as a common cause of swallowing problems (dysphagia) and esophageal dysfunction in adults. The condition arises when inflammatory cells called “eosinophils” wreak havoc on the esophagus by creating inflammation. Over time, the inflamed esophagus begins to undergo abnormal structural changes that can severely impede the passage of food and make it extremely difficult to eat or drink and live a normal life. EoE can lead to increased risk of food impactions, often requiring immediate medical attention. Occurring in 1 to 2 individuals per 10,000, EoE’s prevalence rivals that of other immunologically-related disease such as inflammatory bowel disease and can cause similar debilitating pain and discomfort. While diet changes and medications such as topical corticosteroids work well, matching the best treatment to the right patient remains challenging. Funded by a Digestive Health Foundation grant, Northwestern Medicine researchers led by Nirmala Gonsalves, MD, a faculty member in the Division of Gastroenterology and Hepatology, hope to uncover genetic differences between EoE patients that could lead to better predictors of treatment response and more personalized care. Northwestern Medicine currently has one of the world’s largest cohorts of adults being diagnosed and treated with EoE. Some 700 esophageal tissue samples from these patients, collected at various points in their disease progression, provide an invaluable resource for study. Dr. Gonsalves’ research team plans to mine Northwestern’s comprehensive clinical database (NUCATS) in combination with sophisticated genetic testing and analysis of tissue biopsies. The grant will allow investigators to embark on what will be the largest molecular-phenotype association study of...
Introducing a groundbreaking research technology, the The Digestive Health Foundation became a founding supporter in 2017 of a powerful new resource for digestive health medical research: The Digestive Health Foundation BioRepository. As one of only a few GI biorepositories of its kind in the world, the DHF BioRepository stores, organizes, and makes accessible (digitally, in real time) blood and tissue samples from patients and family members diagnosed with one or more of the digestive disorders treated at the Northwestern Medicine Digestive Health Center. Digestive disease research using the DHF BioRepository will leverage the latest advances in information technology with cutting-edge biologic and molecular research techniques to better understand gastrointestinal diseases and to help develop better treatment options for patients. Across GI sub-specialties, from liver and pancreatic cancers, esophageal diseases/swallowing disorders, inflammatory bowel disease (Crohn’s Disease and ulcerative colitis), GERD, IBS, bariatric surgery, nutritional issues, and many more, the extensive and growing patient network at Northwestern Medicine provides a diverse and valuable resource of participants. After a patient chooses to participate, Northwestern Medicine directly links the patient’s anonymized electronic medical record, physiologic diagnostic test results, imaging results, and patient-directed quality of life indicators to a tissue bank that will include: samples obtained during endoscopy (biopsies), blood, urine, and stool. The DHF BioRepository’s depth of capacity will enable physician scientists around the world to pursue large scale research studies into the mechanisms of digestive diseases. Discoveries about the natural history and progression of digestive disease is providing the insight necessary to develop new diagnostic tools, better treatments, and eventual cures for digestive disease patients and future generations. — The Digestive Health...
