FALL NEWSLETTER 2026   Dear Friends, Thanks to your support, in August we announced funding for two more transformative research projects that could deepen our understanding of why Crohn's disease happens. Both projects, which are already underway, embrace new approaches and will be testing novel treatments in the lab. Read more below about these exciting initiatives from teams at Stanford University and the Mater Research Institute. As always, these updates come directly from the scientists leading the projects you sponsor. This is work happening in real time, led by scientists who believe, like you do, that cures for Crohn's disease are absolutely possible. Your support enables us to fund specialists across different areas of research—from immunology to microbiology and even chemical engineering—who are tackling important questions about Crohn's disease that remain underexplored or have never been addressed before. Every finding and every project brings us one step closer to cures. We salute these teams who are dedicated to improving the lives of IBD patients and you for making their work possible. Sincerely, ANGELA CLARK President and CEO SPONSORED PROJECT UPDATES Investigating Mitochondrial Damage in Crohn's Disease With the support of Propel a Cure, in partnership with the Mendez Family Foundation, the Weinberg and Haileselassie Labs at Stanford University recently began their project to investigate how mitochondrial damage in intestinal epithelial cells may be driving Crohn's disease. The scientists have started growing cells from patients' endoscopic biopsies of the colon or ileum into three-dimensional "organoids." These intestinal patient-derived organoids are small spherical bodies in which the epithelial cells grow and develop, forming organized structures similar to that of the bowel. The team will compare mitochondria (the "powerhouse of the cell") in intestinal organoids from patients with Crohn's disease that is either poorly controlled or in remission with those in organoids derived from healthy individuals. These organoids, which serve as a "disease in a dish" model, will allow investigators to examine the mitochondria under a microscope and measure potential defects in their ability to produce energy in intestinal epithelial cells affected by Crohn's disease. The team has begun growing the first intestinal organoids from a patient with Crohn's disease and a healthy control. Once the researchers establish a baseline for mitochondrial function, they will test how the organoids respond to stress caused by exposure to immune cells, extracellular mitochondria (ExMito), or chemicals produced by microbes. The overall goal will be to develop and test a nonimmunosuppresive therapeutic designed to treat Crohn's disease by preventing mitochondrial damage and the release of ExMito, thereby improving the health of the intestinal epithelium. For the first time, the U.S. Food and Drug Administration has recently approved new drugs for treating diseases, based on testing in organoid models. If the researchers can identify mitochondrial abnormalities and demonstrate that their drug can correct them, this approach could potentially accelerate the path from drug discovery to testing in patients.   Searching for Gut Bacteria That May Protect Against Intestinal Fibrosis The team leading Propel a Cure's newly funded project at the Mater Research Institute (University of Queensland) has been expanding its search for gut bacteria that may protect against intestinal fibrosis in Crohn's disease. Building on its initial screening of 96 bacterial isolates, the team has now screened additional isolates and identified promising candidates that may be able to modify biological processes involved in the development of fibrosis. The researchers are now obtaining additional strains of one of their most promising bacterial species to determine whether its protective effects are unique to the strain originally identified or are shared by other strains of the same species. At the same time, they are continuing to screen additional bacterial isolates in search of other candidates with protective effects. The strongest candidates will then be prioritized for studies to identify which substances they produce are responsible for these effects. This work represents an important early step toward identifying ways to harness the gut microbiome to help prevent or reduce intestinal fibrosis in Crohn's disease patients.   Uncovering Why Immune Cells Struggle to Clear Bacteria in Crohn's Disease As part of Propel a Cure's funded project at UC San Diego, the Ghosh Lab is investigating how immune cells recognize and destroy harmful bacteria and what goes wrong in this process in Crohn's disease. Since the last report, the team has completed additional experiments to strengthen its earlier findings and resubmitted a research paper based on this project to an academic journal, where it is now under review. The lab's earlier work uncovered how NOD2, a protein involved in recognizing bacteria, works with a partner protein called GIV to help immune cells switch from detecting bacteria to destroying them. The researchers found that when this switch malfunctions – as it seems to do in Crohn's disease – a signaling system inside the cells remains active for too long, leaving the cells stuck in recognition mode instead of effectively clearing the bacteria. New experiments have strengthened the evidence for how this failure affects the cell's bacteria-killing machinery. The compartments that contain the bacteria fail to mature properly and become sufficiently acidic and are therefore unable to destroy the bacteria efficiently. Additional analyses independently supported the team's finding that the cells struggle to make the transition from recognizing bacteria to eliminating them. Importantly, the team has shown that this defect can be reversed in laboratory experiments. Several approaches that reduce the activity of a signaling protein called PKA restored the cells' ability to clear bacteria, while artificially increasing another signaling molecule, cAMP, made clearance worse. The researchers also found that delivering a functional portion of GIV restored both signaling control and bacterial clearance. The researchers are now taking an important next step toward understanding how these findings apply to Crohn's patients. Using gene-editing technology called CRISPR, the researchers have begun creating human cell models with specific NOD2 mutations associated with Crohn's. These models will help them determine how different mutations disrupt the bacteria-clearing process and provide a human-based system for screening potential treatments.   Engineering Gut Microbes to Advance Potential IBD Therapies The Woolston Lab at Northeastern University has exciting news this quarter! With funding from Propel a Cure, in partnership with the Mendez Family Foundation, the team is investigating how hydrogen sulfide produced by gut microbes may contribute to intestinal inflammation, a key feature of inflammatory bowel disease. The long-term goal is to help advance new microbiome-based approaches to treating IBD. The researchers have now published the results of its first study using engineered microbes for this project in the journal Metabolic Engineering. The findings support the team's innovative "backward design" strategy: instead of engineering microbes under laboratory conditions and hoping they will work in the gut, the researchers first analyzed which nutrients are available in the gut and used that information to design microbes better suited to function in the body. This approach could help the lab advance its own engineered microbes as potential IBD therapies and may also prove useful for developing other treatments based on gut microbes. The scientists are now preparing for the next phase of the project, which will investigate how much high levels of hydrogen sulfide produced by gut microbes contribute to intestinal inflammation. This phase has involved training lab personnel in the necessary tissue-analysis techniques and refining experimental methods based on what the team has learned so far. VIDEO INTERVIEW NEW LINKS BETWEEN CROHN'S & UC UNCOVERED As part of our continuing series of video interviews with leading IBD researchers, this summer we spoke with Dr. Vincent van Unen about his team's recent findings from a Propel a Cure-funded study. Among the exciting discoveries discussed were how genetic risk factors influence T-cell behavior in IBD, why the underlying mechanisms of Crohn's disease and ulcerative colitis may be more similar than previously thought, and intriguing clues pointing to specific viruses and fungi that may be just the "tip of the iceberg" in identifying the triggers of IBD. Dr. van Unen is an Assistant Professor of Immunology at the Leiden University Medical Center in the Netherlands, where he leads the Vincent van Unen Research Group. He is an expert in mucosal immunology, with a focus on immune-mediated inflammatory disorders. His lab aims to dissect key immune mechanisms driving disease, with the goal of improving diagnostic precision and developing more effective treatments for chronic intestinal conditions. Click here to watch the video. RESEARCH REVIEW A CURATED ROUNDUP OF RECENT IBD RESEARCH AND NEWS "Researchers at the Icahn School of Medicine at Mount Sinai have found that exposure to per- and polyfluoroalkyl substances (PFAS), commonly known as ‘forever chemicals,' during pregnancy and early life is associated with increased intestinal inflammation during childhood." PFAS can be found in nonstick cookware, food packaging, stain-resistant fabrics, and firefighting foam. Article Link: Mount Sinai Newsroom Scientists have discovered a hidden molecular defect that may help explain why flare-ups can return even when IBD patients feel well. Article Link: SciTech Daily Scientists from Weill Cornell Medicine have found that treating intestinal Candida overgrowth with the systemic antifungal fluconazole was associated with changes in the gut microbiome and improvements in disease activity in some patients with mild-to-moderate IBD. The study was small and was not randomized or placebo-controlled, so it cannot establish that fluconazole treats IBD. The researchers are now planning a larger clinical trial to determine whether these findings can be confirmed and which patients might benefit. Article Link: Cornell Chronicle Researchers at McMaster University have developed a bacteriophage (phage) therapy that targets specific bacteria linked to inflammation in some people with Crohn's disease, without disrupting the broader gut microbiome. In preclinical models, the therapy has reduced inflammation. The findings support further research into more targeted, personalized treatments for IBD. Article Link: Medical Xpress HOPE BUILDERS GROWING HOPE. ADVANCING RESEARCH. Hope Builders are the community behind Propel a Cure's year-round investment in promising Crohn's research. With Gratitude to Our Hope Builders Raihaneh Bokharai Kimberly Brown Imran Chaudry Sue Cragg Vince Cvijanovic Dina Fiatarone Manuela Gonzalez-Bueno Stephen Hall Tracy Loewenthal Diana Miguens Natalie Muccioli Federico Nan Gustavo Nonohay Kathleen Pinckney Anthea Pritchard Devin Rasmussen Hellie Saffery Lakshmi Sampath Misty Triplett Angela Vilomar Elizabeth Voisard Eric Voisard An Inside Look at What's Next Exclusive Hope Builder Webinar Coming in November! Hope Builders will be invited to hear from the Stanford team leading Propel a Cure's newly funded research into mitochondrial dysfunction in Crohn's disease and ask questions about their work, including laboratory testing of a potential new treatment. To receive an invitation to this exciting event, become a Hope Builder by making a monthly, quarterly, or yearly gift of any amount. Small recurring gifts can add up to major impact! Employer Matching Opportunities Want to double your donation to help cure Crohn's disease? Some companies will match donations made by their employees to nonprofits like Propel a Cure. Does yours? It's worth asking! Thank you for your support! Thank you for supporting Propel a Cure! If you can get involved, please let us know. We would love to have you as a volunteer! If you'd like more information about Propel a Cure or have suggestions for topics you'd like to see covered in the next newsletter, please contact us at info@propelacure.org. Together we can make a difference! ANGELA CLARK President and CEO info@propelacure.org | PropelaCure.org