Maja Jagodic´s research group
Epigenetic origins and mechanisms in neuroinflammation
Our vision is to understand how epigenome integrates instructions from genetic and lifestyle factors and renders pathogenic immune cells ‘aggressive’ and target brain cells ‘vulnerable’ in persons affected by Multiple Sclerosis.
Our goal is to better understand disease etiology and to improve disease management through personalized treatments and more specific biomarkers.
Multiple Sclerosis (MS) is a chronic inflammatory disease characterized by autoimmune destruction of myelin and neurons in the central nervous system. Today, MS is the most common cause of non-traumatic neurological disability among young adults. Predisposition to MS, similar to other common diseases, irrefutably depends on the complex interplay between genetic and environmental factors. Nevertheless, the epigenetic mechanisms that provide a molecular link between the genome and ‘environmental’ signals and control activity of the genome are still virtually unexplored.
Epigenetic changes are heritable through cell division, controlling gene expression without altering DNA sequence (the genetic code). They provide additional and more flexible level of regulation on the top of the genetic code that can also be modulated by environment. We focus on the role of DNA methylation and non-coding RNAs (ncRNAs), especially microRNAs (miRNA).
Due to their stability, epigenetic changes may provide better etiologic clues and biomarkers. Due to their reversibility, it will become possible to alter unfavorable epigenetic states towards recovery. Therefore, characterizing epigenetic mechanisms gives tremendous opportunities and may open promising insights into pathogenesis of MS, facilitate diagnosis and improve drug development and the treatment of MS patients.
- DNA methylation and ncRNA changes as a functional consequence of etiological genetic (MS risk genes) and environmental (e.g. smoking and vitamin D) factors
- DNA methylation that controls phenotype of pathogenic immune cells and cells targeted in the CNS
- Functional mechanisms of epigenetic changes in neuroinflammation
- Potentials of ‘epigenetic medicine’: biomarkers (e.g. DNA methylation and miRNAs) and treatments (e.g. HDAC inhibitors)
We are utilizing unique and high-quality clinical cohorts in combination with state-of-the-art methods to measure DNA methylation and transcription in discrete cell types, followed by functional studies in experimental models.
For full list of publications please visit Google Scholar link
- The Swedish Research Council (VR)
- EU/Horizon2020 (co-coordinator)
- Karolinska Institutet Senior Research Fellow Grant
- Karolinska Institutet KID-grants
- The regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet
- AstraZeneca/SciLifeLab Joint Research Collaboration (co-applicant)
- The Swedish Brain Foundation
- The NEURO fund
- Mechanism controlling multiple sclerosis risk identified
- Smoking induces DNA methylation changes in multiple sclerosis patients
- Best PI at KI award