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MAJA JAGODIC GROUP

Epigenetic origins and mechanisms in neuroinflammation

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research

Research

We are a highly cooperative international group committed to spearhead translational epigenetics research in Multiple Sclerosis (MS). Our goal is to better understand disease mechanisms and improve disease management through personalized treatments and more specific biomarkers. We conduct an interactive clinically-driven research which combines deep molecular profiling in some of the most competitive clinical materials worldwide together with functional characterization of underlying cellular and molecular mechanisms in advanced experimental models.

 

We strive to understand how the epigenome integrates instructions from genetic and lifestyle factors and make immune cells ‘aggressive’ and target brain cells ‘vulnerable’ in persons affected by MS, by addressing the following questions:

  • What is the epigenetic signature of pathogenic immune cells that trigger neuroinflammation?

  • What is the epigenetic signature of target brain cells underpinning neurodegeneration?

  • How epigenetic mechanisms mediate genetic and lifestyle risk factors?

  • Can epigenetic marks and patterns serve as sensitive and specific biomarkers?

  • Can we utilize targeted epigenome-editing for functional studies and novel therapies?

Consortia & Networks

  • International Multiple Sclerosis Genetics consortium (IMSGC)

  • International Human Epigenome consortium (IHEC)

  • European Consortium (EUbOPEN)

  • European Consortium (MultipleMS)

  • Karolinska Neuroimmunology & Multiple Sclerosis centre (KNIMS)

consortia&networks

Current Research Funding

  • European Research Council (ERC) - ERC grants for research on MS

  • Knut and Alice Wallenberg Foundation - KAW awards

  • EU/Horizon2020 (co-coordinator) - MultipleMS

  • EU/IMI2 – EUbOPEN - EUbOPEN

  • Swedish Research Council

  • Stockholm County Council (ALF Project)

  • Margaretha af Ugglas Foundation

  • Brain Foundation

  • NEURO-fonden

  • Swedish Multiple Sclerosis Research Foundation

  • StratNeuro

currentfunding

News & Awards

Interview with Maja Jagodic in Swedish Television, Rapport (September 3, 2020):  SVT - Jagodic

​Interview with Maja Jagodic, the Knut and Alice Wallenberg Foundation (2020): Developing molecular tools to slow MS

​​KI News (October 16, 2020): Study explains the process that exacerbates MS

European Research Council (ERC) grant (November 29, 2018): ERC grant for research on MS

KI News and Science daily (June 19, 2018): Mechanism controlling multiple sclerosis risk identified

​​Multiple Sclerosis News Today (November 22, 2017): Smoking induces DNA methylation changes in multiple sclerosis patients

Maja Jagodic received the KI Postdoc association Best PI at KI award in 2015: Best PI at KI (2015)

news&awards

Selected Publications

For full list of publications, please visit Google Scholar link.

Zheleznyakova GY, Piket E, Needhamsen M, Hagemann-Jensen M, Ekman D, Han Y, James T, Khademi M, Al Nimer F, Scicluna P, Huang J, Kockum I, Faridani OR, Olsson T, Piehl F, Jagodic M. Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology.

Proc Natl Acad Sci USA, 2021 Apr 27; 118(17): e2011574118. PMID: 33879606

   

Berglund R, Guerreiro-Cacais AO, Adzemovic MZ, Zeitelhofer M, Lund H, Ewing E, Ruhrmann S, Nutma E, Parsa R, Thessen-Hedreul M, Amor S, Harris RA, Olsson T and Jagodic M. Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation. Science Immunology, 16 October 2020, doi: 10.1126/sciimmunol.abb5077. PMID: 33067381

Kular L, Jagodic M. Epigenetic insights into multiple sclerosis disease progression

J Intern Med. 2020 Jul;288(1):82-102.  doi: 10.1111/joim.13045. PMID: 32614160

 

N'diaye M, Brauner S, Flytzani S, Kular L, Warnecke A, Adzemovic MZ, Piket E, Min JH, Edwards W, Mela F, Choi HY, Magg V, James T, Linden M, Reichardt HM, Daws MR, van Horssen J, Kockum I, Harris RA, Olsson T, Guerreiro-Cacais AO, Jagodic M. C-type lectin receptors Mcl and Mincle control development of multiple sclerosis-like neuroinflammation. J Clin Invest. 2019 Nov 14. pii: 125857. doi: 10.1172/JCI125857. [Epub ahead of print] PubMed PMID: 31725411

Kular L, Needhamsen M, Adzemovic MZ, Kramarova T, Gomez-Cabrero D, Ewing E, Piket E, Tegnér J, Beck S, Piehl F, Brundin L, Jagodic M. Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis. Clin Epigenetics. 2019 May 30;11(1):86. doi: 10.1186/s13148-019-0678 1. PubMed PMID: 31146783; PubMed Central PMCID: PMC6543588

International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019 Sep 27;365(6460). pii: eaav7188. doi: 10.1126/science.aav7188. PubMed PMID: 31604244

Ringh MV, Hagemann-Jensen M, Needhamsen M, Kular L, Breeze CE, Sjöholm LK, Slavec L, Kullberg S, Wahlström J, Grunewald J, Brynedal B, Liu Y, Almgren M, Jagodic M, Öckinger J, Ekström TJ. Tobacco smoking induces changes in true DNA methylation, hydroxymethylation and gene expression in bronchoalveolar lavage cells. EBioMedicine. 2019 Aug;46:290-304. doi: 10.1016/j.ebiom.2019.07.006. Epub 2019 Jul 12. PubMed PMID: 31303497; PubMed Central PMCID: PMC6710853

Carlström KE, Ewing E, Granqvist M, Gyllenberg A, Aeinehband S, Enoksson SL, Checa A, Badam TVS, Huang J, Gomez-Cabrero D, Gustafsson M, Al Nimer F, Wheelock CE, Kockum I, Olsson T, Jagodic M, Piehl F. Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes. Nat Commun. 2019 Jul 12;10(1):3081. doi: 10.1038/s41467-019-11139-3. PubMed PMID: 31300673; PubMed Central PMCID: PMC6626021

Ewing E, Kular L, Fernandes SJ, Karathanasis N, Lagani V, Ruhrmann S, Tsamardinos I, Tegner J, Piehl F, Gomez-Cabrero D, Jagodic M. Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression. EBioMedicine. 2019 May;43:411-423. doi: 10.1016/j.ebiom.2019.04.042. Epub 2019 Apr 30. PubMed PMID: 31053557; PubMed Central PMCID: PMC6558224

Kular L, Liu Y, Ruhrmann S, Zheleznyakova G, Marabita F, Gomez-Cabrero D, et al. DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis. Nat Commun 2018 06;9(1):2397

Lund H, Pieber M, Parsa R, Grommisch D, Ewing E, Kular L, et al. Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling. Nat. Immunol. 2018 May;19(5):1-7

Marabita F, Almgren M, Sjöholm LK, Kular L, Liu Y, James T, Kiss NB, Feinberg AP, Olsson T, Kockum I, Alfredsson L, Ekström TJ, Jagodic M. Smoking induces DNA methylation changes in Multiple Sclerosis patients with exposure-response relationship. Sci Rep. 2017 Nov 6;7(1):14589. doi: 10.1038/s41598-017-14788-w. Erratum in: Sci Rep. 2018 Mar 7;8(1):4340. PubMed PMID: 29109506; PubMed Central PMCID: PMC5674007

Zeitelhofer M, Adzemovic MZ, Gomez-Cabrero D3,4,5, Bergman P, Hochmeister S, N’diaye M, Paulson A, Ruhrmann S, Almgren M, Tegnér JN, Ekström TJ, Guerreiro-Cacais AO, Jagodic M. 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 28;114(9):E1678-E1687. doi: 10.1073/pnas.1615783114. Epub 2017 Feb 14. PubMed PMID: 28196884; PubMed Central PMCID: PMC5338504.

selected pubs
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