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Rådinger research group Sahlgrenska Academy
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Rådinger group

Research group
Active research
Project owner
Sahlgrenska Academy, Institute of Medicine, Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre

Financier
VBG group Herman Krefting Foundation for Asthma and Allergy Research, Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Foundation for Strategic Research, Cancer and Allergy Foundation, Wallenberg Centre for Molecular & Transl Med, ALF

Short description

The group is led by Dr. Madeleine Rådinger. Rådinger graduated from the University of Gothenburg with an MSc degree in Molecular biology, and in 2006 she received a PhD in Respiratory Medicine and Allergology at the University of Gothenburg. After her PhD, she took on a postdoctoral position at the Laboratory of Allergic Diseases, National Institute of Allergic and Infection Diseases, the National Institute of Health (NIH), in Bethesda, USA.

Research in the Rådinger group focus on increasing the understanding of the immune system in subgroups of asthma, including the contribution of regulatory microRNAs. The ultimate goal is to identify molecular drivers linked to clinical features in asthma subgroups that can be used for stratification for targeted therapy, diagnosis and identification of new therapeutic targets.

Main research projects

The overall aim of our research is to identify molecular differences in the immune system among different asthma subgroups that could be targeted for new therapeutic intervention and used as biomarkers in the future. We are using a translational approach integrating epidemiology, clinical phenotypes and ex vivo mechanistic studies of samples from human asthmatics. In vivo mechanistic studies in asthma mouse models enable the understanding of the pathophysiology of asthma and is used for translational research. Read more about our main projects below.

Molecular characterization of immune regulation, including epigenetic regulation by microRNAs of immune cells in asthma subgroups

Increased understanding of the immune mechanisms in subgroups of asthmatics, including the contribution of immune regulatory microRNAs, will facilitate patient stratification for targeted therapy, diagnosis and potentially the identification of new therapeutic targets.

Detailed clinically characterized individuals with asthma and healthy control subjects from the West Sweden Asthma Study (WSAS) cohort are used. Mechanistic studies of airway and blood derived immune cells will be performed and the role of microRNAs in the regulation of asthma-relevant mRNA targets of immune processes will be investigated. 

A part of the project involves cell phenotyping of airway and blood derived immune cells and bronchial lavage fluid, using CyTOF and proteomic analysis, respectively. 

Group members responsible for this project:

  • Carina Malmhäll, PhD, Research engineer
  • Julie Weidner, Postdoctoral fellow
  • Jenny Calven, Postdoctoral fellow
  • Emma Boberg, PhD student
  • Roxana Mincheva, PhD, Medical doctor

Identification of new disease-related molecular mechanisms regulating barrier function in primary airway epithelial cells

In this project we focus on the role of the airway epithelium in chronic respiratory diseases with a focus on inflammatory mechanisms observed in asthma. Specifically, we aim at establishing epithelial signatures at different transcriptomic and proteomic levels. This is achieved by using a well-established cell culture system with primary human bronchial epithelial cells that mimics the human central airways. The different signatures are generated from cells treated with disease-relevant stimuli such as cytokines reflective of different immunotypes. The hypothesis is that the airway epithelium is both a driver and an amplifier of the ongoing inflammation, and that the generated signatures can be used for stratification of an otherwise heterogeneous patient population and to identify disease-driving mechanisms.

Further, the involvement of microRNAs, as master post-transcriptional regulators of gene expression, in modulating epithelial barrier function is not well understood. These regulators could provide a source of novel drug targets and biomarkers that could ultimately be used for development of novel therapies through a personalised medicine approach. Thus, a part of this project involves clinical samples from our asthma cohort, WSAS.

Group members responsible for this project:

  • Elisabeth Ax, Industrial PhD student
  • Jenny Calven, Postdoctoral fellow

The role of IL-33 signaling in allergen and non-allergen driven eosinophilic inflammation

Previous research has identified IL-33 and its receptor ST2 as major susceptibility loci in several genome-wide association studies of allergic diseases. In addition, a loss-of-function mutation in the Il33 gene has been reported to be associated with lower number of blood eosinophils and a reduced risk of developing asthma. However, many studies of the IL-33 responsive type 2 innate lymphoid cells (ILC2s) in allergic diseases have focused on barrier tissues such as the lung. Therefore, in this project we aim to investigate the role of the IL-33/ST2 axis and ILC2s in driving bone marrow eosinophilia.

A part of the project involves the role of microRNAs in the regulation of IL-33 driven gene expression in both airways and bone marrow.

Group member responsible for this project:

  • Emma Boberg, PhD student

Key publications

  1. Malmhäll C, Alawieh S, Lu Y, Sjöstrand M, Bossios A, Eldh M and Rådinger M. 2014.
    MicroRNA-155 is essential for TH2 mediated allergen-induced eosinophilic inflammation in the lung. J Allergy Clin Immunol. 2014 May;133(5):1429-38.
    The first study to describe a role for microRNA-155 in the regulation of type 2 mediated allergic eosinophilic inflammation in a mouse model of asthma. 
     
  2. Johansson K, Malmhäll C, Ramos-Ramirez P and Rådinger M. 2017.
    MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation. J Allergy Clin Immunol. 2017 Mar;139(3):1007-1016.
    This is the first study to describe a regulatory role for a microRNA in ILC2 functionality. 
     
  3. Malmhäll C, Weidner J, Rådinger M. 2019. 
    MicroRNA-155 expression suggests a sex disparity in innate lymphoid cells at the single-cell level. Cell Mol Immunol. 2019 Oct 10. doi: 10.1038/s41423-019-0303-4. 
    The first study to describe that human circulating ILCs express microRNA-155 and that this expression is higher in females.