Head: prof dr Annemieke Smet
The mucin isoform landscape in barrier-related diseases
Loss of mucosal barrier integrity contributes significantly to the pathophysiology of mucosal inflammatory diseases. However, the role of mucins as active mediators of barrier function remains poorly understood. Upon inflammation, a defective secreted mucus layer, as characterized by a depletion of secreted mucins, allows microbial species to come in close contact with host cells and elicit inflammation, whereas altered transmembrane mucin expression further translates into a disrupted epithelial barrier. Furthermore, the presence of genetic differences in mucin genes can give rise to a large repertoire of structurally diverse mucin mRNA isoforms via alternative splicing. While most isoforms encode similar biological functions, other have the potential to alter protein function resulting in progression towards disease. Currently, the mucin mRNA isoforms implicated in mucosal barrier dysfunction, is a scientific field to discover.
We recently designed a novel long-read mucin RNA isoform sequencing approach allowing to unravel the complete mucin RNA isoform landscape in a clinical sample (i.e. tissue specimens and blood samples). Therefore, our research focuses on 1) the discovery of the mucin mRNA isoform landscape, mediating mucosal barrier dysfunction in inflammatory bowel diseases (IBD), gastrointestinal cancers (GC and CRC) and respiratory tract infections (RVS, COPD, COVID-19) as well as 2) the different levels of regulation (i.e. microbial and inflammatory triggers) mediating alternative mucin splicing. We implement an unconventional approach encompassing a broadly applicable framework with next-generation sequencing tools, human sample collections and translational models. This work will lead to a new paradigm shift greatly advancing novel applications for disease follow-up at the level of the barrier function and pathology-specific targeting.
MucIRNA: Mucin RNA isoform-based service platform for the monitoring of barrier-related diseases
The mucin research team at the Laboratory of Experimental Medicine and Pediatrics (LEMP) recently developed a novel high throughput sequencing platform encompassing unique mucin RNA isoform panels that map mucosal barrier dysfunction with the heterogeneity of mucosal diseases, like inflammatory bowel diseases (IBD). Because of the game-changing concept towards a central role for the mucosal barrier function in the therapeutic management of diseases, this biomarker-based platform (MucIRNA) performs an in-depth assessment of the mucosal barrier, facilitating the evaluation of efficacy and treatment outcomes in the therapeutic development of IBD.
Core Offering:
The service platform includes:
· Mucin isoform sequencing, using region-specific panels targeting the gastrointestinal tract.
· Clinical interpretation of biomarker profiles to support decision-making in drug development and personalized therapy.
· Functional permeability testing in patient-derived organoids (under development).
· Sample types include intestinal biopsies, organoids, and blood (for future applications).
The offering enables stratification of patient populations, evaluation of therapeutic response, and incorporation of mucosal healing as a biological endpoint.
For more information, contact: annemieke.smet@uantwerpen.be
Proprietary patents in the domain of mucins
The first family (WO2021/013479) encompasses a series of claims covering MUC1 and MUC13 mRNA isoforms as biomarkers for the management of diseases characterized by mucosal barrier dysfunction. The second family (WO2022/003061) includes a series of claims covering the expression levels of mucins and their mRNA isoforms for use in diagnosis, monitoring, prevention and/or treatment of COVID-19. The third patent family (WO2021053238) protects the use of mucin mRNA expression by RSV-infected epithelial cells able to predict the severity of RSV infections in young children. The fourth patent family (WO2025/120137) encloses the intestinal mucin mRNA isoform landscape and the specific isoform panels that associate with inflammation, IBD subtype and anatomical location in the intestinal tract. For more information, see also here.
Key Publications
Van Meer A, Gilis J, Oosterlinck B, Vandamme T, De Man J, De Winter BY, Smet A. Clinicopathological and prognostic significance of mucin signatures in lower gastrointestinal cancer-a systematic review and meta-analysis. Br J Cancer. 2025 Nov 27. doi: 10.1038/s41416-025-03297-7.
Arras W, Oosterlinck B, Gassman J, De Man JG, Jauregui-Amezaga A, De Winter BY, Smet A. Clinical Significance of Mucin Signatures in Inflammatory Bowel Diseases: A Systematic Review of Their Expression Patterns, Polymorphisms, and Post-translational Modifications. Inflamm Bowel Dis. 2025 Nov 24:izaf293.
Arras W, Breugelmans T, Oosterlinck B, De Man JG, Malhotra-Kumar S, Abrams S, Van Laere S, Macken E, Somers M, Jauregui-Amezaga A, De Winter BY, Smet A. The Intestinal Mucin Isoform Landscape Reveals Region-Specific Biomarker Panels for Inflammatory Bowel Disease Patient Stratification. J Crohns Colitis 2025 Mar 5;19(3):jjae155.
Oosterlinck B, Ceuleers H, Arras W, De Man JG, Geboes K, De Schepper H, Peeters M, Lebeer S, Skieceviene J, Hold GL, Kupcinskas J, Link A, De Winter BY, Smet A. Mucin-microbiome sigantures shape the tumor microenvironment in gastric cancer. Microbiome, 2023, 11:86.
Video abstract: https://www.youtube.com/watch?v=SkblRy5eL-0
Breugelmans T, Arras W, Boen LE, Borms E, Kamperdijk L, de Man J, van de Vijver E, van Gils A, De Winter BY, Moes N, Smet A. Aberrant mucin expression profiles associate with pediatric inflammatory bowel disease presentation and activity. Inflamm Bowel Dis 2022 Oct 14:izac217.doi:10.1093/ibd/izac217.
Breugelmans T, Oosterlinck B, Arras W, Ceuleers H, De Man J, Hold G, De Winter BY, Smet A. The role of mucins in gastrointestinal barrier function in health and disease. Lancet Gastroenterology and Hepatology, 2022, 7(5):455-471.
Smet A, Breugelmans T, Michiels J, Lamote K, Arras W, De Man JG, Heyndrickx L, Hauner A, Huizing M, Malhotra-Kumar S, Lammens M, Hotterbeekx A, Kumar-Singh S, Verstraeten A, Loeys B, Verhoeven V, Jacobs R, Dams K, Coenen S, Ariën KK, Jorens PG, De Winter BY. A dynamic mucin mRNA signature associates with COVID-19 disease presentation and severity. JCI Insight, 2021, 6(19): e151777.
Breugelmans T, Van Spaendonk H, De Man JG, De Schepper HU, Jauregui-Amezaga A, Macken E, Linden SK, Pintelon I, Timmermans JP, De Winter BY, Smet A. In depth study of transmembrane mucins in association with intestinal barrier dysfunction during the course of T cell transfer and DSS-induced colitis. J Crohn’s & colitis, 2020, 14(7): 974-994.
Post docs:
PhDs:
Wout Arras: A mucine-isoform based biomarker test for improved detection and treatment of IBD and gastrointestinal cancer
Nikita Hanning: Effect of modulation of the integrity of the intestinal barrier in irritable bowel syndrome - a translational approach
Hanne Voet: Impact of Chronic Obstructive Pulmonary Disease (COPD) severity and disease phenotypes on bronchial epithelial cell immune responses to (non-)infective triggers.
Julie Gassman: Role of the mucin mRNA isoforms and their alternative splicing machinery involved in dysbiosis and mucosal barrier dysfunction in patients with ulcerative colitis
Lien Schrooten: The mucin mRNA isoform landscape and its alternative splicing machinery in colorectal cancer (MUCCOR): a new paradigm in tumour cell death dysfunction
Isabella Da Silva: The mucin mRNA isoform landscape and its alternative splicing machinery in colorectal cancer (MUCCOR): a new paradigm in tumour cell death dysfunction
Alumni:
Tom Breugelmans: Manager Scientific and Procedural Regulatory Affairs