Professor Robert A. Harris
Professor Robert A. Harris (Bob) was born in Harpenden in Southern UK in 1966. He conducted a Bsc.Hons undergraduate degree at Portsmouth Polytechnic, majoring in Parasitology in 1987. PhD studies at University College London studying innate immune agglutinins in Schistosoma host snail species with Terry Preston and Vaughan Southgate as supervisors culminated with a thesis defence in early 1991. A 2.5 year postdoc at the London School of Hygiene & Tropical Medicine in Paul Kaye’s research group ensued, with focus on understanding the intracellular fate of Leishmania spp. protozoans in macrophages. Bob was awarded a Wellcome Trust postdoctoral fellowship that permitted his relocation to the Karolinska Institutet (Stockholm, Sweden) in the spring of 1994. A postdoc period was spent split between the labs of Anders Örn and Tomas Olsson, in which he studied Trypanosoma cruzi and Trypanosoma bruceii protozoan proteins. Bob became an Associate Professor at the Karolinska Institutet in 1999, heralding his establishment as a PI. Bob started to work with autoimmune diseases in 1996 and began study of therapy using live parasite infections or parasite molecules. His research group has developed autoantigen-specific vaccines, defined the effects of post-translational biochemical molecules on autoantigenicity and developed a macrophage adoptive transfer therapy that prevents pathogenesis in several experimental disease models. He became Professor of Immunotherapy in Neurological Diseases in 2013. In recent years research focus has centred on understanding the immunopathogenesis of incurable neurodegenerative diseases, with particular emphasis on development of immunotherapies directed at microglial cells as potential therapeutic paradigms.
Bob Harris CV July 2020
ERIK HERLENIUS GROUP
Development of autonomic control
Immature or deficient autonomic control is a common problem in infants born at a premature age and is of central importance in apneas, secondary hypoxic brain damage and sudden infant death syndrome.
PER ERIKSSON GROUP
For better understanding of disturbances in respiratory control we study early development of cardiorespiratory control, brainstem neural networks and its associations with normal and pathological breathing. The conceptual change introduced by our recent data that endogenous prostaglandins are central pathogenic factors in respiratory disorders and the hypoxic response, open new diagnostic and therapeutic avenues that should significantly better the diagnostics and treatment of newborns and adult patients.
Inflammation is a major culprit in breathing disorders and we hypothesize that by using a newly developed urinary prostaglandin biomarker we can screen, detect and protect against inflammation related breathing disorders.
Our collaborative efforts enable us to move from a clinical problem to molecular understanding of the disease and studies are performed in patients, animal & in vitro models.
Our research is focused on the development of autonomic control with normal and paediatric patients as the target. Autonomic dysfunction in breathing and circulatory control often has its origin in neurodevelopment disorders. Furthermore, our basic research in developmental neuroscience how neural activity and stem cells form activity dependent networks is vital for the development of therapeutic interventions.
CENTER FOR MOLECULAR MEDICINE
MAJA JAGODIC GROUP
Epigenetic origins and mechanisms in neuroinflammation
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)
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
Swedish Multiple Sclerosis Research Foundation
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)
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.