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.
Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis .
Proc. Natl. Acad. Sci. U.S.A. 2017 Feb;114(9):E1678-E1687
Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship.
Sci Rep 2017 Nov;7(1):14589
Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes.
Mult. Scler. 2017 Aug;():1352458517721356
Circulating miR-150 in CSF is a novel candidate biomarker for multiple sclerosis.
Neurol Neuroimmunol Neuroinflamm 2016 Jun;3(3):e219
Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation depends on developmental stage.
Exp. Neurol. 2013 Nov;249():39-48
Acute treatment with valproic acid and l-thyroxine ameliorates clinical signs of experimental autoimmune encephalomyelitis and prevents brain pathology in DA rats.
Neurobiol. Dis. 2014 Nov;71():220-33
Combined sequence-based and genetic mapping analysis of complex traits in outbred rats.
Nat. Genet. 2013 Jul;45(7):767-75
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
Nature 2011 Aug;476(7359):214-9
A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis.
Sci Transl Med 2009 Dec;1(10):10ra21
|Ewoud Ewing||PhD student, Graduate Student|
|Maja Jagodic||Senior researcher, Research team leader|
|Francesco Marabita||Assistant professor|
|Majid Pahlevan||Associated, Postdoc|
|Eliane Piket||PhD student, Research assistant|