{"id":69623,"date":"2025-08-28T13:14:41","date_gmt":"2025-08-28T17:14:41","guid":{"rendered":"https:\/\/www.med.unc.edu\/medicine\/?p=69623"},"modified":"2025-08-28T13:18:46","modified_gmt":"2025-08-28T17:18:46","slug":"shehzad-sheikh-identifies-cadm1-as-a-key-driver-of-gut-inflammation-in-ibd-patients","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/medicine\/news\/shehzad-sheikh-identifies-cadm1-as-a-key-driver-of-gut-inflammation-in-ibd-patients\/","title":{"rendered":"Shehzad Sheikh Identifies CADM1 as a Key Driver of Gut Inflammation in IBD Patients"},"content":{"rendered":"
\"Shehzad
Shehzad Z. Sheikh, MD, PhD<\/figcaption><\/figure>\n

A groundbreaking study co-led by Shehzad Z. Sheikh, MD, PhD, professor of medicine in the UNC Division of Gastroenterology and Hepatology, <\/span>and Matthew N. Poy, PhD, associate professor of medicine with Johns Hopkins University, reveals Cell Adhesion Molecule 1 (CADM1), a surface protein involved in cell-cell adhesion, is significantly elevated in the intestinal tissues of IBD patients. The research also shows CADM1 may fuel ongoing immune activation.<\/p>\n

The findings, published in<\/a> Cellular and Molecular Gastroenterology and Hepatology<\/em>, suggest CADM1 could serve both as a biomarker for disease severity and a potential therapeutic target to reduce inflammation in conditions such as Crohn\u2019s disease and ulcerative colitis.<\/p>\n

\u201c<\/span>Our<\/span> d<\/span>ata show that CADM1 is enriched in myeloid immune cells in the gut and acts as a bridge to activate CD8+ cytotoxic T cells,\u201d said <\/span>Dr. <\/span>Sheikh<\/span>. \u201cThese T cells can damage the intestinal lining, so preventing their activation could reduce disease severity.”<\/span><\/p>\n

Evidence from Human and Mouse Models<\/h3>\n

The study combined several cutting-edge technologies, including RNA sequencing, single-cell transcriptomics, spatial proteomics, and in vivo mous<\/span>e models. The researchers found CADM1 expression was significantly upregulated in the inflamed colons of IBD patients compared to non-IBD controls. Notably, CADM1+ myeloid cells were located adjacent to CD8+ T cells in patient samples, implying a direct role in T cell activation.<\/span>\u00a0<\/span><\/p>\n

To test this mechanism, the team engineered mice with myeloid-specific deletion of Cadm1 and exposed them to DSS, a chemical that induces colitis. These mice showed markedly less intestinal inflammation, fewer activated T cells, and better preservation of intestinal tissue compared to controls. Moreover, treatment with a CADM1-blocking antibody also reduced disease severity in a separate colitis model, providing proof-of-concept for therapeutic intervention.<\/span> These results strongly suggest that CADM1 plays a role in promoting intestinal inflammation. Blocking it could reduce disease severity, offering a potential path for developing new treatments.<\/span><\/p>\n

CADM1 as a Circulating Biomarker<\/h3>\n

Beyond the gut, the study found elevated levels of soluble CADM1 (sCADM1) in the blood of patients with both ulcerative colitis and Crohn\u2019s disease, particularly in those with severe or surgery requiring disease. Recombinant sCADM1 was shown to activate pro-inflammatory STAT3 signaling in human immune cells, further implicating its role in systemic inflammation.<\/span>\u00a0<\/span><\/p>\n

\u201cThis sheds light on a previously underappreciated molecule in IBD pathogenesis,\u201d said Dr. Sheikh. \u201csCADM1 might serve as a blood-based biomarker to identify patients with active disease or predict who is at risk of flares.\u201d<\/span>\u00a0<\/span><\/p>\n

CADM1 has also been implicated in other chronic inflammatory conditions, including type 1 diabetes and chronic kidney disease. This suggests it may be part of a broader inflammatory network.<\/p>\n

Future Directions<\/h3>\n

The discovery of CADM1\u2019s role in IBD has significant therapeutic implications. Most current biologics target cytokines or lymphocyte trafficking. CADM1 represents a new class of target an adhesion molecule that orchestrates cell-cell interactions at the epithelial-immune interface.<\/p>\n

Because CADM1 expression is elevated specifically in immune cells during active disease and because blocking its function appears to reduce inflammation, researchers are optimistic about future clinical translation,” Dr. Sheikh said.\u00a0\u201cWe envision CADM1 inhibition as a novel therapeutic strategy, especially for patients who are refractory to current therapies.”<\/p>\n

This work was supported by <\/span>numerous<\/span> NIH grants, the Helmsley Charitable Trust, the Crohn\u2019s and Colitis Foundation, and Morphic Therapeutics. Read more about Dr. Sheikhs’ lab here.<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

A groundbreaking study co-led by Shehzad Z. Sheikh, MD, PhD, professor of medicine in the UNC Division of Gastroenterology and Hepatology, and Matthew N. Poy, PhD, associate professor of medicine with Johns Hopkins University, reveals Cell Adhesion Molecule 1 (CADM1), a surface protein involved in cell-cell adhesion, is significantly elevated in the intestinal tissues of … Read more<\/a><\/p>\n","protected":false},"author":116983,"featured_media":59089,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[97,92,583],"tags":[],"class_list":["post-69623","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-gastroenterology","category-research","category-research-news","odd"],"acf":[],"yoast_head":"\nShehzad Sheikh Identifies CADM1 as a Key Driver of Gut Inflammation in IBD Patients | Department of Medicine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/medicine\/news\/shehzad-sheikh-identifies-cadm1-as-a-key-driver-of-gut-inflammation-in-ibd-patients\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Shehzad Sheikh Identifies CADM1 as a Key Driver of Gut Inflammation in IBD Patients | Department of Medicine\" \/>\n<meta property=\"og:description\" content=\"A groundbreaking study co-led by Shehzad Z. 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