Forskningsgrupper i Norge
NTNU - Helse Midt Norge, Helse Nord-Trøndelag, Helse More og Rømsdal
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.
Key members
Initially, the clinical part of the project involves the gastroenterology departments at Levanger Hospital, Molde Hospital and St. Olav’s Hospital, in addition to the Children’s and Adolescents’ Clinic at St. Olav’s Hospital.
Key members of CAG-IBD are clinicians and pathologists at the three hospitals in Central Norway, as well as researchers at the Faculty of Medicine and Health Sciences, and the Faculty of Information Technology and Electrical Engineering at NTNU. Among the associated members are national and international research groups and hospitals with extensive experience in IBD.
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.
Researcher from NTNU in CAG IBD:
Gastromedisinsk forskningsgruppe ved Akershus universitetssykehus
Gastromedisinsk forskningsgruppe er ledet av professor Jørgen Jahnsen. Gruppen består av 12 personer, åtte leger (en professor II, en 1.amanuensis, en postdoc, fem PhD-studenter) og fire studiesykepleiere.
Forskningsprofil
Størstedelen av forskningsaktiviteten er relater til inflammatorisk tarmsykdom (IBD), men det forskes også på cøliaki og leversykdommer. Vi er involvert i basalforskning, så vel som klinisk forskning og medikamentutprøving i diverse legemiddelstudier. I basalforskningen fokuserer vi på prognostiske faktorer for sykdomsforløp og behandlingseffekt, samt mekanismer bak utvikling av IBD-relatert tarmkreft. I kliniske studier ser vi på effekten av medikamentmålinger ved biologisk behandling, behandling med intravenøst jern, mikrobiotas rolle og ekstrakorporal fotoferese som fremtidig behandlingsmulighet.
Forskningsprosjekter – IBD-relaterte
- IBD-CHARACTER: A multi-modal integrated biomarker study (IBD-Character Consortium) funded by EU´s 7th Framework Program.
- NOR-DRUM: A NORwegian multicentre randomised controlled trial assessing the effectiveness of tailoring infliximab treatment by therapeutic DRUg Monitoring.
- Nor-vaC: Prospective, observational study to evaluate immunogenicity and safety following SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases receiving immunosuppressive therapy.
- Colorectal neoplasia in IBD: A prospective study comparing endoscopic surveillance with regular clinical follow-up.
- Photopheresis in the treatment of patients with Crohns’ disease using 5-aminolevulinic acid.
- Gut microbiota – its relation to clinical outcome and mucosal barrier functions in IBD.
- Clinical implementation and safety of high dose i.v. iron treatment in gastroenterology.
- IBSEN II: This is a multi-center study, including five hospitals in the Helse Sør-Øst region, which has included 321 adult and pediatric IBD patients and controls.
- IBSEN III: This is a multi-center study, including 20 hospitals in the Helse Sør-Øst region, with the aim to include 2400 adult and pediatric IBD patients and controls.
- Inflammatory bowel disease and persistent organic pollutants (POPs): A translational research approach.
- Molecular drivers and inhibitors of colorectal cancer in IBD. This project is a close collaboration with Hilde Nilsen group at EpiGen Institute Ahus. different stages of carcinogenesis in IBD.
- Identification of predictive biomarkers for personalised treatment of patients with Crohn’s disease. Single cell RNA sequencing (scRNAseq) and spatial transcriptomics.
- BLUE study: Incidence, treatment and outcome of gastrointestinal bleeding due to peptic ulcers and erosions.
- Clinical trials. The unit has a high activity in conducting clinical trials, both phase 2 and 3, initiated by the pharmaceutical industry to evaluate efficacy and safety for new medical treatments in IBD.
Leder: Jørgen Jahnsen, MD, PhD, professor og overlege, Akershus universitetssykehus Gastromedisinsk avdeling og UiO. E: jorgen.jahnsen@medisin.uio.no.
Barnegastroenterologisk forskningsgruppe ved Akershus universitetssykehus
Forskningsprofil
Barnegastroenterologisk forskningsgruppe arbeider med basalmedisinske og kliniske studier knyttet til mage-tarm- og tarmflora (mikrobiota). Hovedfokuset er inflammatorisk tarmsykdom (eng. IBD).
Interesseområder: Diagnostisering og karakterisering av IBD, prognose, skreddersydd behandling fra debut, biologisk behandling , ernæringsbehandling ved Crohns sykdom (EEN – eksklusiv enteral ernæring og CDED -Crohns Disease Exclusion Diet), tretthet og utmattelse (fatigue), og tarmfloraens (mikrobiomets) rolle.
Forskningsprosjekter – IBD-relaterte
Gruppen er engasjert i følgende studier:
- Mikrobiomet (tarmens bakterieflora) ved inflammatorisk tarmsykdom – sammenheng med diagnose, sykdomsaktivitet og sykdomsforløp. Postdoktor prosjekt sammen med Epigen på Ahus. “Human og mikrobiell crosstalk” hos pasienter med IBD. Vi ser på mikrobiota i feces og biopsier, både tilstedeværelse og gen ekspresjon/ funksjon.
- Mikrobiota ved COVID -19. ”Precision microbiota profiling of COVID-19 in adolescents. Focus on diagnosis, prognosis and long-term effects”. Vi ser på feces (samarbeid med BioME) og blodmikrobiomet, spesielt i forhold til utvikling av fatigue.
Samarbeidsprosjekter
- IBSEN III (Inflammatory Bowel Disease in South Eastern Norway)
- DOUBLE PIBD: Europeisk samarbeid om pediatriske IBD pasienter får dobbeltbehandling med to biologiske medikamenter
- VEOIBD: Europeisk samarbeid med genanalyser og undersøkelser av barn med tidlig debut av IBD.
- SPEED UP: Europeisk samarbeid, bruk av ustekinumab hos barn med IBD
- EURKIDS: Europeisk registerstudie av pediatrisk IBD
- EOSINOFIL ØSOFAGITT: Norsk pediatrisk samarbeid om diagnostikk og behandling av eosinofil øsofagitt
- Kognisjon og psykisk helse hos barn med Down og glutensensitivitet
- IBD Character EU multinational collaborative study
Leder: Christine Olbjørn, MD, PhD, postdoktor og overlege, Akershus Universitetssykehus, Barne og ungdomsklinikken. E: chrisolb@gmail.com.
Gastroenterologisk forskningsgruppe ved Stavanger universitetssjukehus
Forskningsprofil
Gastroenterologisk forskningsgruppe arbeider med studier knyttet til mage-/tarm- og leversykdommer. Hovedfokuset er inflammatorisk tarmsykdom (eng. IBD).
Interesseområder: sykdomsutvikling og mekanismene bak dette, hva som kjennetegner pasienter som responderer godt på medisinsk behandling, biologisk behandling, tretthet og utmattelse (fatigue), tarmfloraens (mikrobiomets) rolle. Forskningen består av både basalmedisinske og kliniske studier.
Forskningsprosjekter – IBD-relaterte
Gruppen er engasjert i følgende studier:
- Stavanger Universitetssjukehus IBD studie (SUSI).
Substudier/-prosjekter:
– Fatigue ved inflammatorisk tarmsykdom.
– Serumkonsentrasjonsmåling av infliximab og adalimumab ved IBD – effekt på sykdomsaktivitet, fatigue og livskvalitet.
– Optimalisert biologisk behandling med infliximab ved akutt alvorlig ulcerøs kolitt.
– Antistoffproduksjon mot biologisk medikament.
– Mikrobiomet (tarmens bakterieflora) ved inflammatorisk tarmsykdom – sammenheng med sykdomsaktivitet og sykdomsforløp.
Samarbeidsprosjekter: - Blastocystis’ rolle ved inflammatorisk tarmsykdom.
- BIOSTOP-studien (seponering av biologisk behandling).
- NOR-DRUM-studien (Del A) (serumkonsentrasjon infliximab).
- SCAN-IBD studien (kolorektal cancer ved IBD).
- TITRATE studien (akutt alvorlig ulcerøs kolitt).
- SONORESCUE-studien (UL evaluering i akutt alvorlig ulcerøs kolitt).
Leder: Tore Grimstad, MD, PhD, overlege, førsteamanuensis Stavanger universitetssjukehus. E: tore.bjorn.grimstad@sus.no
IBD-forskning ved Haukeland universitetssjukehus og Universitetet i Bergen
Gastromedisinsk seksjon på HUS har mange ulike interesseområder som bl.a forskningsprosjekter på ultralydmetoder, irritabel tarm, avansert endoskopi, bukspyttkjertel og inflammatoriske tarmsykdommer (IBD). Mesteparten av vår IBD- forskning er tilknyttet forskningsgruppen «Bergen Research group for UltraSound in gastroEnterology (BRUSE)» som ligger under Klinisk Institutt 1 ved Universitetet i Bergen.
Gastrointestinal ultralyd (GIUS) ved IBD
På grunn av endringer i behandlingsregimer og behandlingsmål ved inflammatoriske tarmsykdommer er det et økende behov for tett monitorering. Bedring i billedkvalitet og -oppløsning på ultralydskannere har ført til at man kan se veggen i gastrointestinaltraktus tydelig og skille den fra omliggende strukturer. Siden GIUS også er en pasientvennlig metode har den funnet sin plass i oppfølgingen av IBD-pasienter.For å bedre standardiseringen og øke bruken av GIUS i den daglige oppfølgingen av pasienter er det behov for nye kliniske studier der man se på relevante pasientpopulasjoner og sammenlikner med aksepterte referansestandarder. Vi har nylig utviklet og validert en ultralydscore for Crohns sykdom og har også bidratt i utviklingen av en score for ulcerøs kolitt. Vi holder nå på med longitudinelle observasjonsstudier hvor vi ser kliniske utfall ved inflammatoriske tarmsykdommer og avhengig av resultat vil dette kunne føre til prosjekter hvor vi bruker GIUS som verktøy for kliniske beslutninger. Oppdatert liste over forskninsgprosjekter.
Noen pågående forskningsprosjekter
Lokalt initierte:
- Sonorescue- Ultrasonografi for utvelgelse av pasienter som trenger «rescue»-behandling for akutt alvorlig ulcerøs kolitt
- SonoDOCc –Bruk av ultralydkontrast ved Crohn’s sykdom
- Betydning av tykkelse av tarmvegg og lag i tarmveggen målt med ultralyd for kliniske utfall ved CD
Samarbeidsprosjekter:
- USE-IT: internasjonal studie organisert gjennom «International Bowel Ultrasound (IBUS) group. (https://ibus-group.org/research/helmsley-use-it-project/ )
- BIOSTOP-studien inkl Ultralydundersøkelser ( Prelaps-studien)
Andre IBD-prosjekter:
- Evaluering av norsk versjon av sjekkliste på IBD poliklinikken
- IBD og nefritt-:under planlegging
Leder BRUSE: Odd Helge Gilja, Professor og overlege.
Haukeland Universitetssjukehus og Universitet i Bergen
Leder IBD forskning: Kim Nylund, 1. amanuensis, overlege.
Haukeland Universitetssjukehus og Universitet i Bergen
Leder klinisk IBD-gruppe: Hilde Løland von Volkmann, PhD, overlege.
Haukeland Universitetssjukehus
Forskning
