Principal Investigator: Paulius V. Kuprys, MD, PhD, Fellow, Physician-Scientist Training Program, Division of Gastroenterology and Hepatology, Northwestern Medicine, Northwestern University Feinberg School of Medicine One percent of the U.S. population grapples with the chronic symptoms of inflammatory bowel disease (IBD). On the rise around the globe, IBD has gained steady traction in countries adopting “Western” diets of ultra-processed foods, saturated fats, and low fiber. While growing evidence supports the impact of diet in both the onset and relapse of IBD, its direct relationship to gut inflammation remains unclear. Current dietary guidelines recommend fresh foods such as those found in the popular Mediterranean diet. But generalized diet plans often fall short in meeting the diverse tastes and restrictions of IBD patients. Supported by this year’s DHF grant, Dr. Kuprys’ team intends to create a unique IBD specific dietary measurement tool in a first-of-its-kind study. The investigators will ask participants with IBD undergoing colonoscopy to provide a 24-hour recall of what they ate one to two weeks after the procedure. Using that information to calculate an IBD-specific healthy eating index (HEI), the researchers aim to link HEI scores to the health of the colon. Quantifiable data from this invaluable work could offer a reliable roadmap for IBD patients to use in their daily food...
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...
Division of Gastroenterology and Hepatology Northwestern Medicine/Feinberg School of Medicine Center for Artificial Intelligence and Mathematics in Gastroenterology The Center for Artificial Intelligence and Mathematics in Gastroenterology (AIM-GI) is a first of its kind program developed in a division of Gastroenterology. Artificial Intelligence and Machine Learning have the potential to vastly improve our ability to accurately predict, diagnose and treat our patients living with digestive diseases. Through collaboration with engineers at the McCormick School of Engineering and physician scientists at the Feinberg School of Medicine at Northwestern University, our team has been incorporating mathematical modeling and advanced programming to study the mechanisms that lead to poor gastrointestinal function. This work led to the development of a more formalized center that focuses on three main initiatives. Development of virtual organs which can be used to study the effects of surgery and medications; Development of new hybrid diagnostic tools using AI and machine learning to enhance diagnosis; Using machine learning and neutral networks to predict disease outcome. Although this is a new program, we have already had success developing an NIH funded Center of Research Expertise (CORE) and we have also developed new AI prototypes that can improve diagnostic accuracy and reliability of motility tests. This work is supported by the generosity of the Digestive Health Foundation and these funds help provide the computational power and expertise required to continue to develop these innovative tools. Our goal is to continue invent and develop new approaches and our partnership with the Digestive Disease Foundation will continue to allow us to grow and evolve this...
Principal Investigator: Jonah J. Stulberg, MD, PhD, MPH | Salva Balbale, PhD The national opioid crisis continues to adversely affect millions of lives, including a growing number of individuals with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Studies have suggested that long-term opioid use among IBD patients can result in serious detrimental effects on GI function. Opioid use disorders in this population have also been linked to longer hospital stays, increasing health care costs, and deaths. Yet a comprehensive understanding of the opioid usage and pain management needs of these patients remains elusive. Additionally, no published studies have explored the decision-making process that IBD providers use when prescribing opioids. Dr. Stulberg’s study will lay the groundwork for developing best practices to optimize the use of opioids for IBD patients. The researchers will conduct interviews with IBD providers, in addition to focus groups with IBD patients to ensure all voices are heard and incorporated in future opioid safety efforts to enhance the care and pain management for patients with inflammatory bowel disease. (Dr. Stulberg led a previous DHF-funded study in 2017 that tracked and greatly reduced opioid prescriptions and risk of misuse in GI surgery...
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...
