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
TOMAS OLSSON GROUP
Clinical and experimental neuroimmunology
A large part of our research focuses on mechanisms involved in the disease pathogenesis of MS.
Since MS is caused by inflammation and the inflammation can be controlled, the MS disease should in principal be curable or at least preventable to a large extent. Some of the currently available therapies are in fact able to dampen the relapse rates up to 70 %. However, these therapies broadly interfere with the immune system, which is needed for the host defense against infections, and may be risky over a long term prospects. Therefore, the primary goal is to achieve a more detailed knowledge on the exact modes and mechanisms in which the immune system is allowed to attack the nervous system in order to develop much more precise therapeutic interventions.
Both environmental factors and gene variants contribute to the cause of MS. The genes involved are likely to be many (the candidate genes are around hundred today) and therefore may differ between different individuals with MS. This has been a working hypothesis for decades, but with recent technological and intellectual developments this can be properly studied.
Our General Aim is to understand the genetic and environmental causes of MS by translational approach integrating molecular genetics and functional studies in rodent models of MS and non- specific CNS damage with large scale studies in clinical MS materials.
Our detailed research plan:
Fine dissection of polymorphic genes regulating rat models of MS and inflammatory neurodegeneration after nerve trauma using advanced intercross lines (AIL), a heterogeneous stock (HS) and recombinant congenic mapping under the assumption that interspecies conserved mechanism may be of relevance for human neuroinflammatory disease.
By comparative genetics, study if the same gene, or genes in the same pathway, are of relevance in human disease.
Functionally dissect these pathways in rodents, and also study potential therapeutic intervention.
Study potential gene-environment interactions in a large ongoing case-control study.
Participate in a large international endeavour on un-biased whole genome scanning of a very large MS case-control cohort (the International Multiple Sclerosis Genetics Consortium, IMSGC). And in follow up studies in the included Swedish material, study relations between genetic variants, gene expression and gene-environment effects.
Identification of polymorphic genes regulating rat models of MS and inflammatory neurodegeneration after nerve trauma
By comparative genetics, is the same gene/pathway relevant in human disease
Study potential therapeutic interventions
Study potential gene-environment interactions in a large ongoing case-control study
Identification of genes regulating MS in patients (the International Multiple Sclerosis Genetics Consortium, IMSGC) and study relations between genetic variants, gene expression and gene-environment effects
Montgomery S, Hiyoshi A, Burkill S, Alfredsson L, Bahmanyar S, Olsson T. Reply to: Concussion may not cause multiple sclerosis. Ann Neurol. 2017 Oct;82(4):652-653. Abstract not available.
Steri M, et al. Overexpression of the Cytokine BAFF and Autoimmunity Risk. N Engl J Med. 2017 Apr 27;376(17):1615-1626.
Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234.
Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017
Häggmark-Månberg A, Zandian A, Forsström B, Khademi M, Lima Bomfim I, Hellström C, Arnheim-Dahlström L, Hallböök T, Darin N, Lundberg IE, Uhlén M, Partinen M, Schwenk JM, Olsson T, Nilsson P. Autoantibody targets in vaccine-associated narcolepsy. Autoimmunity. 2016 Sep;49(6):421-433.
Hedström AK, Alfredsson L, Olsson T. Environmental factors and their interactions with risk genotypes in MS susceptibility. Curr Opin Neurol. 2016 Jun;29(3):293-8.
Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjöberg R, Forsström B, Bredenberg J, Lima Bomfim I, Holmgren E, Grönlund H, Guerreiro-Cacais AO, Abdelmagid N, Uhlén M, Waterboer T, Alfredsson L, Mulder J, Schwenk JM, Olsson T, Nilsson P. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proc Natl Acad Sci U S A. 2016 Feb
Gustafsson M, Gawel DR, Alfredsson L, Baranzini S, Björkander J, Blomgran R, Hellberg S, Eklund D, Ernerudh J, Kockum I, Konstantinell A, Lahesmaa R, Lentini A, Liljenström HR, Mattson L, Matussek A, Mellergård J, Mendez M, Olsson T, Pujana MA, Rasool O, Serra-Musach J, Stenmarker M, Tripathi S, Viitala M, Wang H, Zhang H, Nestor CE, Benson M. A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases. Sci Transl Med. 2015 Nov 11;7(313):313ra178.
Moutsianas L, et al. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat Genet. 2015 Oct;47(10):1107-1113.
International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013 Nov;45(11):1353-60.
Ayoglu B, Häggmark A, Khademi M, Olsson T, Uhlén M, Schwenk JM, Nilsson P. Autoantibody profiling in multiple sclerosis using arrays of human protein fragments. Mol Cell Proteomics. 2013 Sep;12(9):2657-72.
Khademi M, Dring AM, Gilthorpe JD, Wuolikainen A, Al Nimer F, Harris RA, Andersson M, Brundin L, Piehl F, Olsson T, Svenningsson A. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers. PLoS One. 2013 May 7;8(5):e63172.
Sandberg-Wollheim M, Olsson T. Cerebrospinal fluid oligoclonal bands are important in the diagnosis of multiple sclerosis, unreasonably downplayed by the McDonald criteria 2010: Yes. Mult Scler. 2013 May;19(6):714-6.