IBD Research Group
The Inflammatory bowel diseases research group (IBD) studies disease mechanisms in inflammatory bowel diseases, and aims to use this knowledge in clinical medicine.
The group’s work is based on a large, still expanding research biobank with tissue samples and blood fractions collected over several years. Research is done using all standard laboratory methods and cutting-edge techniques such as e.g advanced histological imaging, human organoids for mechanistic studies and transcriptomics/genomics.
Example projects are the effect of genetics on the inflammatory process, how hypoxia influences the epithelial barrier, the action and regulation of mucosal antimicrobial peptides and how the diffuse neuroendocrine system interacts with immune signaling in inflammatory bowel diseases. This work is done in collaboration with researchers at NTNU, researchers and clinicians at hospitals within the Central Norway Regional Health Authority, and several national and international partners.
The IBD research group is a translational environment, engaging clinicians and biologists in patient-centered research from bedside to the laboratory bench.
The IBD group receives large grants from The Liaison Committee for education, research and innovation in Central Norway. Some of the members in the research group are part of Centre of molecular inflammation research (CEMIR) at the Department of Clinical and Molecular Medicine (IKOM), the Inflammatory bowel diseases research group.
The research group has close collaboration with the hospitals in the region through the Clinical Academic Group (CAG) Precision medicine in inflammatory bowel disease.
LINK: https://www.ntnu.edu/ikom/inflamboweldiseas#/view/about
CAG IBD – Precision medicine in inflammatory bowel disease
The main goal of a CAG is to bring the research closer to the patients, and produce «patient-centered» results to be quickly implemented in the clinic.
A CAG is an Academic Clinical Research Group, which consists of researchers and clinicians from different universities and hospitals. The aim is to solve a concrete health problem and increase the quality within the field of clinical practice. CAG provides a strong professional network across healthcare settings from universities to everyday clinical work.
The first CAGs in Norway were established at the initiative of the Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, according to a Danish model. The CAGs are supported both by the university (NTNU) and by the health trust (Central Norway Regional Health Authority), and intend to build strong clinical-academic interdisciplinary competence.
Current challenges in IBD
Diagnosis, treatment and multidisciplinary care of patients with IBD (ulcerative colitis and Crohn´s disease) is an important part of the activity of gastroenterology departments. Most patients are diagnosed with IBD at a young age and this means, for many, decades of active disease and treatment. In addition, a well-known problem in the clinic is that the course of the disease and the effect of treatments are difficult to predict. This heterogeneity is also a challenge in IBD research.
Our research team will use the CAG award to contribute to the development of precision medicine (individualized approach) for IBD patients by continuing our translational research on carefully controlled patient material.
Clinical collaboration
CAG-IBD will contribute to unite gastroenetrology departments in the region and experienced IBD researchers in one joint group for patient-focused translation research with the National Patient Organization for Digestive Diseases (LMF) as support.
Our goal
From the clinical perspective, the goal is that all departments establish standardized diagnostics, follow-up and treatment decision protocols for patients with IBD. The clinical process will train clinicians in evidence-based gastroenterology, and bring non-university hospitals towards cutting-edge IBD diagnostics and treatment. In parallel, the project seeks to train IBD nurses to ensure optimal patient care.
We will collect clinical information and biological samples from diagnosis and at set times throughout the course of the disease. The project will create a particularly well-controlled, longitudinal biobank for IBD research aimed at clarifying prognostic factors, predicting treatment response and understanding disease mechanisms. This cohort thus meets the widely acknowledged need for precisely characterized clinical and biological research material, and will create opportunities for research collaboration both nationally and internationally.
1. Histopathology Unit
The Histopathology Unit explores the use of histological indexing and both traditional and advanced molecular pathology to identify patient subgroups, and integrates this with clinical data, genetic/genomics and patient-derived ex vivo studies. This will facilitate in-depth understanding of underlying biological differences and disease heterogeneity.
As part of this, we collaborate with Dept. of Pathology, St. Olavs Hospital, to develop the use of digital computational pathology to enable automated and more accurate image analysis of tissue samples for research and in the clinic. Our aim is to identify clinically relevant histopathological markers and provide pathologists with complementary tools to help release the highly unexplored potential for more precise and personalized diagnostics in IBD.
Objectives for ongoing research activities:
- Correlate histological indexing with endoscopic and clinical parameters and determine its prognostic and predictive value for short- and long-term clinical outcomes.
- Characterize mucosal immune cells in different mucosal compartments segmented by code-free deep learning image analysis in IBD-patients stratified with histological indexing.
- Identify and characterize histopathological traits, genomic-/genetic-, immunological- and molecular mechanisms illuminating the underlying differences between IBD-patient subgroups based on stratification with histological indexing.
- Use open-source software and tools for digital computational pathology and artificial intelligence (deep convolutional neural networks) to further develop models for automated image analysis of tissue sections.
- Identify, characterize, and validate clinically relevant histopathological and immunohistochemical markers.
2. Genetics and Genomics Unit
In this unit, we explore how genes and gene expression in IBD patients differ from healthy controls. We are also interested in what gene variants and gene expression within the IBD patient cohort can tell us about each individual’s disease prognosis and treatment response.
We perform large genome and gene expression analyses of patient samples and patient-derived cell cultures and correlate these results with clinical observations identifying genes and processes that can be used clinically for improved, more precise treatment and diagnosis. Identified processes and gene variants are followed up to better understand the mechanisms underlying the observed difference. All studies are performed in close collaboration with the other units within CAG-IBD, as well as the clinic.
Objectives for ongoing research activities:
- Identify genetic variants that predispose for a complicated disease course and poor treatment outcome in IBD.
- Characterize the mechanisms underlying the effect of these genetic variants, for example through sequence variants in miRNA binding sites.
- Evaluate if the identified genetic variants are efficient and reproducible biomarkers for use in the clinic.
- Elucidate epithelial involvement in regulating the intestinal inflammation seen in IBD through gene expression analyses of epithelial cells from IBD patients and experiments in patient-derived epithelial cell lines.
- Characterize the role of serotonin and epithelial serotonin reuptake transporter in intestinal fibrosis.
- Investigate how epithelial regeneration is balanced in an inflamed intestinal environment.
3. Cell and Molecular Biology Unit
In this unit we explore microbiota-host interactions and IBD patient-derived ex vivo model systems for individual characteristics and differences in immunological and drug responses. We perform a range of advanced molecular analyses of patient material; and use state-of-the-art patient-derived models for functional studies to understand how interactions between microbiota, intestinal epithelium and immune cells disturb or contribute to inflammation, regeneration of the intestinal epithelium and mucosal healing in IBD. The work is performed in close collaborations with the other research units in the CAG-IBD.
Objectives for ongoing research activities:
- Characterize the presence and frequency of commensal and pathogenic microbiota (bacteria and viruses) in IBD patients for possible associations with disease remission or aggravation.
- Investigate signal transduction and cellular responses in patient-derived cells to understand how interactions between signals from microbiota (viruses, bacteria, fungi), intestinal epithelium and immune cells contribute to IBD pathobiology.
- Refine experimental platforms allowing co-cultures of intestinal cells, immune cells and microbiota; and use patient-specific material as tools in IBD-precision medicine.
- Characterize organoids from a cohort of diseased including individuals with unique phenotypic or genetic variations to better understand IBD heterogeneity.
- Establish methods for genetic modification of patient-derived organoids.
- Use approved and investigational IBD-drugs to both gain insight about their modes of action, and as experimental tools to understand heterogeneity in treatment responses.
- Evaluate patient-derived organoids as drug testing platform and correlate with clinical outcome.
