RESEARCH FOR A CURE
Propel A Cure is an all-volunteer nonprofit organization that raises funds for innovative research focused specifically on identifying the underlying cause or causes of Crohn’s disease, the first step in the development of a cure. Funding for projects comes primarily from patients, their families, friends, and caregivers. Propel a Cure carefully allocates these donations so that they will be used solely for promising research that will ultimately lead towards a cure for Crohn’s disease.
Ghosh Lab, University of California, San Diego
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In April 2025, Propel a Cure pledged $100,000 to the Ghosh Lab at The University of California, San Diego, partially funding their 2-year breakthrough study, “Modulation of Dysfunctional Sensing and Signaling in Crohn’s Disease”. The team will be focusing on how the protein NOD2 interacts closely with another molecule called GIV, which acts like a brake to prevent overactive inflammation and support bacterial clearance in the human body. In Crohn’s disease, certain genetic changes in NOD2 disrupt this teamwork, leaving the gut vulnerable to persistent inflammation, infection, and damage.
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Through this research, the Ghosh Lab aims to uncover how NOD2 and GIV work together to protect the gut, what happens when this partnership fails, and how to fix it.
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1. Learning How NOD2 and GIV Interact: They will investigate when and where these molecules connect inside immune cells and what strengthens or weakens their bond. This will help explain the precise role they play in sensing bacteria and controlling inflammation.
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2. Exploring the Consequences of Their Teamwork: By testing specific genetic changes and drugs in lab experiments, they will determine how NOD2 and GIV work together to clear harmful bacteria and regulate inflammation. They’ll also examine how disruptions to this partnership may lead to Crohn’s disease.
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3. Testing New Insights in Disease Models: Using advanced tools like "gut-on-a-chip" models and experiments in mice and human tissues, the team will see how their findings translate to real-world Crohn’s disease scenarios.
By discovering how to restore the partnership between NOD2 and GIV, the Ghosh Lab hopes to pave the way for new treatments that not only manage symptoms but address the root causes of Crohn’s disease. This work could lead to breakthroughs in understanding gut immunity, offering hope to millions affected by this challenging condition. The majority of this groundbreaking study has been funded; please help us fully sponsor the second year by giving to Propel a Cure.
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UPDATE: June 2025
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To better understand how NOD2 and GIV interact, over the past few months the team worked with mice and immune cells called macrophages. Mice that didn’t have GIV developed a type of gut disease that looked very similar to Crohn’s disease in humans, including swelling, tissue damage, and problems with the natural balance of gut bacteria. Most importantly, the team focused on a common version of NOD2 called "1007fs", which is found in many Crohn’s patients. This version is broken — it’s missing a key piece — and the researchers have now found out why that matters: It can’t connect to GIV. Without that connection, the immune system can’t do its job right, and bacteria aren’t cleared properly. This leads to more inflammation and damage in the gut.
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This is the first time scientists have clearly shown how this precise Crohn’s risk mutation, which was discovered originally in 2000, disrupts the immune system’s ability to clear bacteria.
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Now that the team understands this key piece of the puzzle, they are excited about the next step: exploring ways to fix or replace this broken connection between NOD2 and GIV as a new way to treat Crohn’s disease. Beyond mice, this team has the unique ability to test all their findings and hypotheses as well as potential drug-like small molecules and peptides in mini human guts called organoids. The team plans on doing those studies next.​​
Woolston Lab, Northeastern University
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In February 2025, Propel a Cure, in partnership with the Mendez Family Foundation, awarded a $100,000 grant to Northeastern University’s Woolston Lab for its cutting-edge proposal, "Defining the Role of Microbial Hydrogen Sulfide in Intestinal Inflammation."
Hydrogen sulfide is a molecule produced primarily by gut microbes and is associated with intestinal inflammation. Past studies have implicated it as a player in inflammatory bowel disease (IBD), but to date its precise role has been poorly understood. The Woolston Lab has engineered unique synthetic probiotic strains to use in this study that would be tested to gain insights into how and whether excessive production of hydrogen sulfide helps trigger IBD inflammation and what part it may play in disease progression.
Even more exciting, the research team has discovered that one of their newly developed strains has demonstrated particular promise in reducing the production of hydrogen sulfide in human-derived ex vivo studies, potentially leading to a new therapeutic that could treat or prevent IBD. Currently, there are no FDA-approved medicines targeting hydrogen sulfide for treating IBD. The development of a therapeutic to degrade toxic and pro-inflammatory intestinal hydrogen sulfide would be transformative for IBD patient care. Should preclinical animal testing prove successful, the Woolston Lab is already affiliated with a spinoff biotech startup – Concordance Therapeutics – which would be well positioned to bring such a therapeutic to clinical trials. This truly groundbreaking study will represent the first attempt to use engineered microbes to regulate sulfide levels in the gut microbiome.​
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UPDATE: June 2025
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The team engineered bacteria in the lab designed to try to produce excess hydrogen sulfide in the animal gut. They have now tested their engineered bacteria in animals, observing a greater than 5-fold increase in intestinal hydrogen sulfide. This is a critical milestone because elevating hydrogen sulfide levels is experimentally difficult due to its gaseous nature. The team now has a tool capable of elevating intestinal hydrogen sulfide levels – mimicking what is seen in Crohn’s patients – that will help us understand its fundamental role.
In the next phase of this work, the Woolston Lab will be able to use their engineered bacteria to study how high levels of hydrogen sulfide impact Crohn’s pathology, which is a significant step forward.
Promakhos Therapeutics, Boston
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In February 2024, Propel a Cure awarded $100,000 to Promakhos Therapeutics for their innovative proposal, "Validating the Role of Mucosal Innate Immune Deficiency in Crohn’s Disease." Promakhos is a Boston-area startup housed in the Pagliuca Harvard Life Lab, an incubator lab co-managed by Harvard University and Lab Central.
This team's exciting project centers on the hypothesis that the mucosal innate immune response is not activated correctly in Crohn’s patients. Based on their observations, up to 90 percent of patients with active disease have lower than normal levels of innate immune activating molecules. This would appear to mean that the innate immune response is not functional and therefore impairs antimicrobial responses in Paneth cells, leading to defective bacterial clearance.
By reactivating the innate immune signal, Promakhos believes that the defective communication between the gut microbes and the immune system could be restored in the majority of Crohn’s patients. Ultimately, they hope that their preclinical work that Propel a Cure will help fund and that will be completed in two years or less can pave the way for a curative, non-immunosuppressive oral treatment that can remediate faulty innate immune signaling in the gut.
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UPDATE: June 2025
Over the past few months, the researchers transplanted stool from patients with active Crohn’s disease and reduced levels of the innate immune-activating molecules into mice to establish a humanized mouse model of bowel inflammation. Encouragingly, the team observed that mice transplanted with stool from patients showed a 4-fold reduction in fecal levels of the bacterial molecules, compared with mice transplanted with stool from healthy individuals. Once the Crohn’s patient gut microbiome was established in the mice, the researchers induced acute colon inflammation to evaluate the therapeutic effect of their compound. In this model, inflammation worsens for 3-4 days and then heals over the next 10 days or so. Starting at the peak of inflammation (Day 4), the researchers administered their compound once per day through the mouth to restore the natural activity of the bacterial molecules in the mouse gut.
Although the study has not been finalized, the team is excited to share that the administration of their therapeutic compound led to a reduction in symptoms by 73% on Day 8 and by 92% on Day 10, while placebo-treated mice showed a 43% and 67% reduction by days 8 and day 10, respectively. These differences were statistically significant, suggesting that the restoration of the natural levels of the bacterial molecules with their compound greatly accelerated healing of acute colon inflammation in these mice. The next steps are to further analyze the results of this study and to explore different doses of this compound in this new Crohn’s patient humanized mouse model.
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UPDATE: February 2025
Over the past few months, their scientists have completed the analysis of additional stool samples from Crohn’s patients and are happy to share that their original findings have been validated. They have now analyzed 47 samples from patients and 26 samples from healthy volunteers. They observed that, overall, stool from patients with Crohn’s disease showed a 3-fold reduction in the bacterial molecule level compared with healthy volunteers. Moreover, patients with active disease showed a stronger reduction (5-fold reduction) in the level of these molecules than patients with inactive disease, while some individual patients showed a reduction of up to 10-fold.
The researchers have now started the next phase of the project. This involves transplanting stool from patients with active Crohn’s disease and reduced levels of the bacterial molecules into mice to establish a more clinically relevant and humanized mouse model of bowel inflammation. Encouragingly, the team has observed that mice transplanted with stool from patients showed a 4-fold reduction in fecal levels of the bacterial molecules, as compared with mice transplanted with healthy control stool. The team now aims to further expand on this study and to use this mouse model to further validate the therapeutic effect of their candidate drug before they move towards the clinic.
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UPDATE: October 2024
The researchers are close to finishing their analysis of 25 new stool samples from patients with Crohn’s disease from their Boston-area hospital partner. They expect to complete this analysis before the end of the year and share the results with us in the next update.
The next phase of the project will involve transplanting into mice Crohn’s patient stool that reflects a 10-fold reduction in bacterial molecule levels that promote immune control and wound healing versus that seen in healthy controls. This will allow the development of a clinically relevant mouse model of bowel inflammation. With this model, the team will be hoping to further validate the therapeutic effect of their candidate drug molecule before they move towards the clinic.
The Promakhos team has also further engaged with researchers at KU Leuven in Belgium to analyze more stool samples from patients with Crohn’s disease. Finally, they are exploring using colon organoids established from patients to evaluate the therapeutic effect of their candidate drug molecule.
These colon organoids maintain the state of the colon lining in patients and are the closest human system for assessing the therapeutic effect of a new drug before evaluating it in the clinic. Using these organoids, the team aims to estimate the clinical doses that will most likely have therapeutic effect in patients.
UPDATE: August 2024
The Promakhos researchers discovered that up to 85% of Crohn’s patients at a Boston hospital carry low levels of certain bacterial molecules that promote immune control and wound healing in the gut, most likely due to microbiome changes (initial study with 25 patients). Ultimately, the team aims to restore the levels of these ligands to the levels observed in healthy individuals and thinks that this could be disease modifying. The team has been working with their collaborator in Boston to further validate their findings by expanding with 25 new patient samples.
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Besides their collaboration in Boston, the Promakhos team has now engaged two other clinical centers in Belgium and France to explore whether they can test additional stool samples from Crohn’s patients. The first is the IBD center at KU Leuven in Belgium, led by Prof. Dr. Séverine Vermeire. The second is the Center for Gastroenterology and Nutrition at the Hospital Robert Debré in France, led by Prof. Dr. Jean-Pierre Hugot. Both Dr. Vermeire and Dr. Hugot were enthusiastic about the idea and have expressed interest in working with Promakhos. The team is now working on drafting agreements to partner with these centers.
UPDATE: May 2024
Promakhos Therapeutics' initial discovery utilized 25 Crohn's patient fecal samples from a leading Boston hospital. They are now obtaining additional fecal samples to further expand on their findings. The team will determine whether the bacterial molecule levels are similarly reduced across patients, or whether there are differences in levels depending on disease location (ileal, colonic, ileocolonic) or treatment status.
The team is now working to categorize and test the newly received fecal samples. Later, they aim to transplant Crohn's patient stool that reflects the 10-fold reduction in bacterial molecule levels into mice to develop a clinically relevant mouse model of bowel inflammation. They will then use this model to further validate the therapeutic effect of their candidate drug in order to move to the clinic. These results are also expected to confirm whether the team can use the levels of these bacterial molecules as a biomarker to predict which patients might benefit the most from the treatment.​​
Mark M. Davis Lab, Stanford University
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For its first grant, Propel a Cure in partnership with the nonprofit Cure for IBD awarded $58,000 toward a groundbreaking study at the Mark M. Davis Lab at Stanford University, entitled "Identification of Circulating and Tissue-Resident CD4+ T Cells Specific for Disease-Driving Antigens in Crohn's Disease". The project focused on T-cell receptors (TCRs) in the gut of Crohn’s patients. In immune-mediated diseases, TCRs bind to certain antigens that appear foreign, flagging them for destruction.
The Davis Lab furthermore explored the specific TCRs involved in Crohn’s and made progress in better understanding their behavior by finding patterns and grouping certain sections of their sequences into clusters using a unique algorithm they created that had successfully worked for other diseases under study.
The lab also used an algorithm to study human leukocyte antigens (HLAs), proteins that are on most of the cells in the body. HLAs present antigens to TCRs, triggering a reaction if the antigen appears foreign.
We excitedly await the publication of the results of this project, which will help the scientific community better understand some of the important cellular mechanisms at work in Crohn's disease. The study has been submitted to a prominent academic journal and is awaiting peer review.
MOVING FORWARD
As we continue to move forward, we need your financial support now more than ever to fund research for a cure (or cures). Please consider a one-time or recurring donation so that together we can make prevention, better treatments, and cures a reality! It will take all of us, but we truly believe the goal is achievable and we can prevent and stop so much suffering. Propel a Cure is a 501(c)3 nonprofit whose Board members receive no salaries, work out of their homes, and frequently dip into their own personal funds to cover our minimal overhead costs. All donations are tax-deductible for U.S. residents, and no donation is too big or too small.