Principal Investigator: Ronen Sumagin, PhD, Associate Professor of Pathology, Northwestern Medicine, Northwestern Feinberg School of Medicine Made from living cells, biologic medications offer crucial disease mitigation to individuals with inflammatory bowel disease (IBD) when other drugs don’t work or have stopped working. Although biologics may improve symptoms and control infection, some 40% of patients on biologics will still experience ongoing inflammation in the colon, increasing their risk for disease relapse or complications requiring surgery or hospitalization. Better predicting a patient’s response to biologic therapy and/or their likelihood of sustaining remission could greatly inform IBD treatment choices, improving patients’ chances for better health. A type of white blood cell, neutrophils have typically been known to be major drivers of intestinal inflammation. Recent studies suggest, however, that not all neutrophils are the same and some neutrophils may actually help maintain colon health and improve response to biologic therapy. Thanks to previous work, in part supported by DHF, Dr. Sumagin’s team identified a unique subset of beneficial neutrophils found in IBD remission patients. Marked by the expression of surface marker CD74, these unique neutrophils feature distinct anti-inflammatory properties. This year’s DHF funding will help the investigators further expand their understanding of how CD74+ neutrophils work in and why they develop in IBD. Advancing this knowledge offers promise for using these cells as prognostic biomarkers of sustained remission for IBD patients to safely stop biologic therapy and/or as targets to prevent disease recurrence in the...
Principal Investigator: Vasilios Kalas, MD, PhD, Physician-Scientist Training Program Fellow (PGY-4), Division of Gastroenterology and Hepatology, Northwestern Medicine, Northwestern Feinberg School of Medicine Co-Investigator: Gabriel Rocklin, PhD, Assistant Professor of Pharmacology, Northwestern University Feinberg School of Medicine Inflammatory bowel disease (IBD) affects the lives of more than 2.5 million Americans, including many children and adolescents. A serious, chronic autoimmune disease, IBD is characterized by the body’s immune system going into overdrive and attacking its own tissue, causing gut inflammation and infection, diarrhea, rectal bleeding, and bowel obstructions. IBD drugs help tamp down the inflammation, but they also can weaken the immune system. This broad swipe approach to treatment, in combination with the disease, can leave patients vulnerable to infection and cancers. The molecular structure of IBD medications plays a major role in their effectiveness. While small molecules make therapeutics like prednisone an easy-to-swallow oral drug, these drugs typically have low potency because they are unable to target the unique inflammatory causes of a patient’s IBD. On the other hand, large antibody drugs, like Humira or Stelara, offer higher potency and specificity, but they must be injected or infused at a clinic. Supported by this year’s DHF grant, Dr. Kalas’ team plans to use advances in artificial intelligence (AI) to engineer a new kind of drug molecule that has both high potency AND high specificity, and can also be easily taken by mouth. The investigators will create miniprotein blockers that target the receptors TNFR1 and claudin-2 that cause IBD inflammation. This revolutionary research aims to develop more effective oral therapies with fewer side effects that could be a gamechanger for...
THIS STUDY UTILIZES THE DHF BIOREPOSITORY Principal Investigator: Marie-Pier Tétreault, PhD, Assistant Professor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine Gastroesophageal reflux disease (GERD) affects up to 27% of the adult U.S. population, resulting in more than seven million patient visits annually. Over time, GERD leads to serious complications such as erosive esophagitis, Barrett’s esophagus and esophageal cancers. However, how GERD functions at the molecular level is unclear, making it difficult to develop better treatments for patients living with this condition. This year, DHF is supporting Dr. Marie-Pier Tétreault’s work in identifying the molecular mechanisms that drive the development and progression of GERD, in the hopes of changing the future for patients living with this destructive esophageal condition. DHF funding will enable researchers to utilize state-of-the-art, single-cell RNA technology to rapidly look at the precise gene expression patterns of tens of thousands of cells in hopes of uncovering and identifying rare populations of diseased cells. Previous successful DHF funding of the Tétreault team uncovered valuable new insights and created new technology in profiling the unique cells involved in eosinophilic esophagitis (EoE) and scleroderma esophageal disease. This year, the research team is focusing on the widespread disease of GERD with a focus on new, critical treatment options for patients to decrease the risks of major esophageal complications, including...
Principal Investigator: Keith C. Summa, MD, PhD, Instructor of Medicine (Gastroenterology and Hepatology), Northwestern Medicine, Northwestern Feinberg School of Medicine A chronic autoimmune condition affecting over 1.6 million people in the U.S., inflammatory bowel disease (IBD) causes ongoing pain, infection, and debilitating symptoms for many people around the world. An umbrella term encompassing Crohn’s Disease, ulcerative colitis, and unspecified colitis, IBD is a growing global public health problem with more than 70,000 new cases, many in children, diagnosed each year in the U.S. Intestinal inflammation occurs in combination with sleep problems, fatigue, and circadian rhythm disturbances in patients with IBD. In fact, studies have found increased alternations in the circadian clock system of IBD sufferers. Yet the exact molecular mechanisms linking sleep to IBD remain unclear. This year’s grant from DHF funds a study led by Dr. Keith Summa to take a deep dive into the ways sleep and circadian rhythms influence gut health. His team will study, in a mice model of colitis, if and how sleep and circadian disruptions trigger gut microbial changes and activate signaling pathways to accelerate damaging inflammation. The researchers hope this novel scientific avenue yields better insight into the underlying causes of IBD, leading to more effective therapeutic strategies to improve patients’ quality of...
Principal Investigators: Ezra N. Teitelbaum, MD, MEd, Assistant Professor of Surgery (Gastrointestinal), Northwestern Medicine, Northwestern Feinberg School of Medicine Eric S. Hungness, MD, S. David Stulberg, MD, Professor of Advanced Surgical Education, Professor of Surgery (Gastrointestinal) and Medical Education, Northwestern Feinberg School of Medicine Hiatal hernias are a digestive disorder that has plagued patients for decades, developing when the stomach abnormally protrudes into the chest through a hole in the diaphragm. These hernias often cause heartburn, swallowing problems, vomiting, and sometimes worse. While laparoscopic hiatal hernia surgery is the gold standard for stitching closed the opening to fix hiatal hernias, this approach has a historically dismal hernia recurrence rate of up to 50%. This is due, in part, to the only suture material currently available for hernia repair that can often inadvertently pull through the tissue when under tension. Used for other types of hernias, permanent mesh reinforcement is the only alternative and cannot be used for hiatal hernias due to the risk of mesh erosion into the esophagus. Supported by this year’s DHF grant, Dr. Ezra Teitelbaum’s team plans to investigate the potential of new mesh sutures (Duramesh™) invented by Northwestern University researchers and just now available at Northwestern Memorial Hospital. The novel hybrid makeup of Duramesh™ offers the complementary advantages of both new, flexible mesh and traditional, strong suture materials. This research offers great promise for reducing hernia recurrence after repair to improve patient results and prevent the need for risky redo operations and/or the return of distressing, destructive digestive...
