WINTER NEWSLETTER 2026     Dear Friends, Thank you for making 2025 the best year yet for Propel a Cure! Your support is proof that a small all-volunteer organization, together with patients, family members, and friends, can make an outsized impact on Crohn's disease research. Only a couple of months ago, the Ghosh Lab at UC San Diego generated international headlines by solving a 25-year old mystery surrounding the role of the most common genetic mutation associated with Crohn's disease. The pilot study associated with the Ghosh Lab project was funded by Propel a Cure donors and will be the basis for at least two additional upcoming studies that are laying the groundwork for new therapeutic approaches for Crohn's patients. You can read more about this lab's remarkable progress in the updates below. RESEARCH UPDATES UC SAN DIEGO TEAM UNLOCKS BACTERIAL CLEARANCE MECHANISMS The Ghosh Lab at UC San Diego is the recipient of a two-year $100,000 grant from Propel a Cure. Using advanced computer models powered by machine learning, these scientists, with the assistance of the Institute for Network Medicine, have uncovered a deeper pattern behind why immune defenses fail in chronic inflammatory diseases such as inflammatory bowel disease (IBD). Their recently published work in The Journal of Clinical Investigation showed that harmful bacteria can overwhelm key gut immune cells called macrophages when a critical molecular partnership breaks down. This partnership involves an immune sensor called NOD2 and a helper protein called GIV. When GIV levels are reduced—or when NOD2 carries mutations that prevent this molecular "handshake"—macrophages lose their ability to clear bacteria. This discovery has been foundational. It has provided the first clear explanation for why people carrying certain NOD2 mutations face an extremely high risk of developing Crohn's disease. Instead of eliminating harmful microbes, their macrophages allow bacteria to persist and multiply, driving chronic inflammation. In follow-up work, the team uncovered how this molecular handshake protects immune cells from being hijacked. Bacteria attempt to take control of a universal cellular messaging system called cAMP—similar to an internal alarm network. When pathogens succeed, cAMP levels rise, disabling the macrophages' ability to kill microbes and calm inflammation. When the NOD2–GIV partnership is intact, immune cells regain control, cAMP levels are restrained, and threats are cleared. The researchers mapped when and where this battle for control occurs, showing it is central to resolving infection. This work is currently under peer review prior to publication. This latest advance goes even further. In a new perspective article, the researchers show that these molecular battles are not unique to IBD or to a single immune pathway. Instead, many microbes exploit the same short molecular "codes" to confuse immune signaling, while the body has evolved matching systems to detect and neutralize these tricks. This reframes immunity not just as detecting microbes, but as constantly verifying whether cellular messages are trustworthy. Importantly, this opens the door to new therapies aimed at restoring immune logic itself—rather than simply suppressing inflammation.   LAB FURTHER CONFIRMS EFFECTIVENESS OF ENGINEERED MICROBES Propel a Cure, in partnership with the Mendez Family Foundation, is also funding research at Northeastern University's Woolston Lab with a $100,000 grant. This past quarter, the team there continued to demonstrate progress toward understanding the role of the molecule hydrogen sulfide (H2S) in Crohn's disease and therapeutic development. They have now established that the lab's specially engineered microbes can deliver H2S in the intestine more effectively than existing chemical methods, suggesting that these microbes are an ideal tool for testing the elevation of intestinal H2S in laboratory mice. This is a critical step toward understanding the possible role of H2S in Crohn's. The scientists have also begun testing the engineered microbes in dextran sulfate sodium (DSS)-induced Crohn's mouse models (as opposed to normal mice versions). These specialized mice mimic the effects of IBD seen in human patients. Using their H2S-producing and -consuming microbes, the team is further investigating how the elevation or reduction of H2S impacts Crohn's disease pathology. They are thus far encouraged by study results and, in the future, will be experimenting with the delivery of different levels of H2S, as well as expanding the number of mice in the study. WEBINAR HIGHLIGHTS PROPEL A CURE- SPONSORED PROJECT AIMS This past November, Dr. Benjamin Woolston of Northeastern University, who is spearheading a Propel a Cure-sponsored study on the role of hydrogen sulfide in intestinal inflammation, presented an exclusive hour-long webinar on the project to our Hope Builder recurring donors. Among the highlights was his description of how engineered microbes being used in this study may lead to a transformative therapeutic for IBD patients. Propel a Cure's current Hope Builder donors include Raihaneh Bokharai, Sue Cragg, Vince Cvijanovic, Natalie Muccioli Emery, Dina Fiatarone, Stephen Hall, Diana Miguens, Gustovao Nonohay, Kathleen Pinckney, Anthea Pritchard, Devin Rasmussen, Hellie Saffery, Lakshmi Sampeth, Misty Triplett, and Eric Voisard. To receive invitations to research roundtables and access to other exclusive events and behind-the-scenes news, sign up to become a Hope Builder recurring donor by visiting propelacure.org/donate and selecting the monthly, quarterly, or yearly option. Click here to view a one-minute highlight of Dr. Woolston's webinar, as presented recently on Propel a Cure's social media. BOARD ANNOUNCEMENT LEADING RESEARCHER NAMED TO PaC SCIENTIFIC ADVISORY BOARD We are excited to welcome Dr. Brian Coombes to Propel a Cure's Scientific Advisory Board. This body advises our organization on the scientific merits of proposed projects and distribution of research funds, as well as on other substantive scientific issues or questions as needed. Dr. Coombes is a Professor and Chair of the Department of Biochemistry and Biomedical Sciences at McMaster University (Canada). He is an internationally recognized expert in infectious disease and host-microbe interactions, focusing on gut health, chronic inflammatory disorders, and antibiotic drug discovery. His research combines molecular microbiology and pre-clinical models to uncover how bacterial pathogens influence disease and immunity, particularly in the gut. Coombes Lab collaborates widely with industry partners on novel therapeutics for Crohn's disease and antibiotic resistance. Dr. Coombes is a fellow of the American Academy of Microbiology and has published over 220 papers and abstracts. Of his appointment, Dr. Coombes says, "I'm very happy to be helping this organization dedicated to cures for Crohn's disease." VIDEO INTERVIEW IBD FERTILITY AND PREGNANCY As part of its continuing series of video interviews with leading IBD researchers, Propel a Cure met with Dr. Uma Mahadevan to discuss the newest findings and recommendations on contraception, fertility, pregnancy, and breastfeeding for IBD patients. If you, your partner, family member, or friend with IBD is considering pregnancy at some point, this interview is a must-see! Click here to watch the video. Dr. Mahadevan, a gastroenterologist and professor of medicine at the University of California, San Francisco, is a global expert on the management of pregnancy and drug safety in IBD patients. She chaired the Global Consensus Statement on the Management of Pregnancy in IBD in Inflammatory Bowel Disease and is the principal investigator of the ongoing PIANO study (Pregnancy in IBD and Neonatal Outcomes). Detailed information on the topics discussed in the video is available by visiting the PIANO website at PIANOstudy.org. PARTNERSHIPS NEW PHILANTHROPIC PARTNERSHIP PROGRAM We are excited to announce the launch of Propel a Cure's Philanthropic Partnership Program. This initiative is for companies and individuals who would like to give back to the IBD community by more formally aligning with Propel a Cure through investing in innovative Crohn's disease research targeting cures. Various benefits tiers are available for partners. To learn more, please email us at info@propelacure.org. FATHOM: OUR NEWEST CORPORATE PARTNER Propel a Cure would like to thank Fathom, our newest corporate partner, for its generous support. Fathom is an AI wellness companion designed specifically for IBD. You can find more details at the Fathom website.       AI Wellness Companion for IBD MISTIC PERFUMES: PAYING IT FORWARD Mistic Perfumes was founded by a high school student living with Crohn's disease specifically to support research for cures. The company, which gives 100% of its profits to Propel a Cure, recently made its second donation, which will be designated for a cutting-edge research project to be announced later this year. To learn more, visit misticperfumes.com. HIGHLAND PARK HIGH SCHOOL SUPPORTS PROPEL A CURE Every year since 1994, the student body and staff of Highland Park High School (Highland Park, IL) have chosen a nonprofit organization as the focus of a month-long Charity Drive that raises funds and awareness. We are excited and honored to announce that we have been selected as the beneficiary of their 2026 effort! Several PaC Board members recently participated in the school's January 16th kick-off assembly for the campaign, which will conclude in mid-February. Students will lead a full calendar of events, with all proceeds going toward Propel a Cure-sponsored Crohn's research. Fundraising efforts will range from a silent auction to a "winter wonderland" dance to a sports day that will include team competition. Propel a Cure is grateful and inspired by the passion of these young supporters and looks forward to bringing you coverage and results of the HPHS Charity Drive in our Spring 2026 e-newsletter. If you would like to help these incredible students who are raising funds for Crohn's research, visit hpcharitydrive.org. RESEARCH REVIEW NEWS ABOUT CROHN'S AND IBD According to a large international study of newly diagnosed Crohn's and ulcerative colitis patients, IBD begins with a major shift in gut bacteria, even before treatment starts. Beneficial, anti-inflammatory bacteria drop off, while oxygen-tolerant bacteria (including some normally found in the mouth) increase. Article Link: MEDICAL NEWS & LIFE SCIENCES A team led by King's College (London) has discovered how a specific group of immune cells in the gut -- ILC3s -- activates a powerful signaling molecule that they hope to better harness to calm inflammation and repair tissue in IBD patients. Article Link: KING'S COLLEGE NEWS CENTRE Scientists have established that smoking fuels mouth bacteria to grow in the gut, triggering an immune response that worsens Crohn's disease. They hope to develop new therapies from this key finding. Article Link: SCIENCE DAILY In a major new study about fistula biology, Oxford researchers have discovered that Crohn's "fistulas are lined by concentric rings of 'rogue' fibroblasts – cells that normally maintain tissue structure - that have become reprogrammed to act like cells involved in early fetal gut development. This out-of-context activity causes fibroblasts near the tract surface to destroy the surrounding tissue, promoting tunneling, while deeper fibroblasts produce stiff, fibrotic material that stabilizes and maintains the tunnels." Article Link: UNIVERSITY OF OXFORD 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