Principal Investigator: Ronen Sumagin, PhD, Associate Professor of Pathology, Northwestern Medicine, Northwestern Feinberg School of Medicine Ulcerative colitis (UC) causes inflammation in the innermost lining of the colon. From belly pain to diarrhea and bleeding, this type of inflammatory bowel disease (IBD) can take a serious toll on patients’ overall health and lead to life-threatening complications. While most IBD therapies, including biologics, improve symptoms, many individuals still have low-grade tissue inflammation that puts them at risk for disease or infection. Implicated in driving intestinal inflammation, white blood cells have long been lumped together as bad actors. Yet, as it turns out, not all immune cells are alike. Thanks to previous support from DHF, Dr. Sumagin’s team has identified “healer” neutrophils in UC patients in remission. Frequently found in non-inflamed tissue, this unique subset of immune cells may be strong candidates for promoting colon health and predicting response to IBD treatments. In 2024, the Sumagin lab barely missed winning a $1.7 million NIH grant by a slim 1% application score. Using this year’s DHF award as important bridge funding, the researchers will focus on characterizing these CD74+ neutrophils in human UC tissue and preclinical animal models to determine if they truly improve gut health. Advancing this breakthrough work could bring new hope for UC patients in achieving disease remission and avoiding repeated hospitalizations, surgery, and life-threatening complications from active...
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: Ronen Sumagin, PhD, Assistant Professor of Pathology (Experimental Pathology), Northwestern Feinberg School of Medicine When conventional medications, such as corticosteroids or 5-aminosalicylates, fail to work in IBD patients, biologics that block a critical inflammatory molecule called tumor-necrosis-factor alpha (TNFα) are commonly prescribed. However, one third of patients receive no relief from these biologic drugs, and other patients become resistant to the therapy over time, forcing physicians to pursue other avenues of treatment for their patients. In previous work, the Sumagin lab and other researchers established the important role of immune cells, called neutrophils, in IBD. Recent studies revealed that in inflamed tissue there are diverse neutrophil populations with distinct functions. With the DHF grant, Dr. Sumagin is using innovative single-cell sequencing to map neutrophil diversity in IBD. His research team seeks to determine whether specific neutrophil subtype(s) dictate resistance to anti-TNFα therapy. This effort offers great promise for unraveling new disease processes and identifying predictive biomarkers of treatment outcomes or drug targets to prevent anti-TNFα resistance in IBD patients. Physicians could then predict ahead of time which drugs may work for their patients living with IBD. This valuable insight could potentially decrease symptom or disease flares, as a result of drug inefficacy or resistance, in the long-term treatment of...
Immune cells called neutrophils protect our body against invading pathogens, but when they accumulate in tissue, they can also cause recurring injury to cells of the gastrointestinal tract. The resulting chronic inflammation in the colon is a hallmark of inflammatory bowel diseases (IBDs). It is also a well-recognized risk factor for the development of colorectal cancer. Dr. Sumagin’s preliminary findings suggest that neutrophils may influence the transformation of normal cells into cancerous ones by increasing the occurrence of mutations, inhibiting the ability of cells to repair themselves and ultimately promoting cancer development. The team is focusing on specific mutations in the tumor suppressor gene TP53—the most frequently mutated gene in Colitis-associated colon cancer. The goal of this project will be to determine whether immune cell-mediated inflammation results in specific mutations in TP53 and to identify these mutations. If successful, this study will open the door to future prognostic biomarkers of inflammation-induced colorectal cancer. Funding will partially support the research personnel involved in this work and for purchases of essential reagents needed to complete these...
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...
