Maja Jagodic´s research group

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Epigenetic origins and mechanisms in neuroinflammation

We aim to characterize epigenetic mechanisms that control ´aggressiveness´ of the pathogenic cells and ´vulnerability´ of the target cells and mediate effects of etiological factors in Multiple Sclerosis, with the prospect of better understanding disease etiology and improving disease management. 

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.

Research projects

  • 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.

Selected publications

Acute treatment with valproic acid and l-thyroxine ameliorates clinical signs of experimental autoimmune encephalomyelitis and prevents brain pathology in DA rats.
Castelo-Branco G, Stridh P, Guerreiro-Cacais A, Adzemovic M, Falcão A, Marta M, et al
Neurobiol. Dis. 2014 Nov;71():220-33

Parent-of-origin effects implicate epigenetic regulation of experimental autoimmune encephalomyelitis and identify imprinted Dlk1 as a novel risk gene.
Stridh P, Ruhrmann S, Bergman P, Thessén Hedreul M, Flytzani S, Beyeen A, et al
PLoS Genet. 2014 Mar;10(3):e1004265

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats.
, Baud A, Hermsen R, Guryev V, Stridh P, Graham D, et al
Nat. Genet. 2013 Jul;45(7):767-75

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
, , Sawcer S, Hellenthal G, Pirinen M, Spencer C, et al
Nature 2011 Aug;476(7359):214-9

A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis.
Jagodic M, Colacios C, Nohra R, Dejean A, Beyeen A, Khademi M, et al
Sci Transl Med 2009 Dec;1(10):10ra21

Group members

Ewoud EwingGraduate Student
Maja JagodicSenior researcher
Maja JagodicResearch team leader
Lara KularPostdoc
Maria NeedhamsenBioinformatician
Eliane PiketResearch assistant
Sabrina RuhrmannResearch assistant on study grant
Sabrina RuhrmannGraduate Student
Galina ZheleznyakovaPostdoc