Biography
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
About
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
Research
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.
Read more
Contact: communication@cmm.se
CENTER FOR MOLECULAR MEDICINE
LARS MAEGDFESSEL GROUP
Non-coding RNAs in vascular biology and medicine
About
Lars Maegdefessel’s Molecular Vascular Medicine group at the Center for Molecular Medicine is focused on the therapeutic and biomarker potential of non-coding RNAs in vascular disease and its underlying (patho-)mechanisms, such as atherosclerosis, aneurysm formation, inflammation, and thrombosis. His research team utilizes unique human biobank material and various pre-clinical experimental models to unravel novel treatment and detection methods on a molecular basis to combat the burden of cardiovascular diseases.
Major research focus
Tremendous efforts have been initiated to elucidate the molecular and pathophysiological characteristics of cardiovascular disease (CVD), which has developed into the most prominent factor of morbidity and mortality in our aging society. Despite these efforts to reduce the burden of CVD, the identification of the complex genetic and epigenetic regulatory circuit, as well as sufficient steering and intervention, remains a great challenge in basic cardiovascular research and everyday clinical practice. The traditional method of drug design and biomarker discovery, involving enzymes, cell surface receptors, and other proteins, has not really impacted the treatment and detection of CVD to a greater extent in the recent past, which is mainly due to the sensitive nature of the targeted system.
In this dismaying scenario, the discovery of an entirely new method of regulation and recognition by non-coding RNAs (e.g., microRNAs, lncRNAs) and their validation as markers and modulators of pathological conditions, provides new hope for innovative therapy and disease recognition approaches. The Molecular Vascular Medicine lab at Karolinska utilizes unique human biobank material (tissue and plasma) of different CVDs. Most recently the group is exploring the role of microRNAs and lncRNAs in stable and unstable atherosclerotic plaques (from patients with symptomatic and asymptomatic carotid stenosis), aortic aneurysms (thoracic and abdominal), peripheral vascular occlusive disease (PVOD), in-stent restenosis (ISR), as well as transplantation and radiation vasculopathy. Candidate ncRNAs and their putative gene (mRNA) targets and proteins are profiled and detected through different transcriptomic (RNA sequencing, microarrays), proteomic, epigenomic and genetic analyses applications.
Discoveries from human profiling studies are extensively investigated in pre-clinical models of CVD, allowing the lab to better understand the physiological and pathological function and dysfunction of ncRNA modulation. In vitro studies are deployed for in-depth mechanistic studies in disease-relevant cell types and conditions.
Collaborations and Funding
Several in-house collaborators exist, including Professor Per Eriksson and Docent Joy Roy (aneurysm disease), Professor Ulf Hedin (atherosclerotic plaque vulnerability), Professor Göran Hansson (experimental atherosclerosis research), Professor Thomas Renné (thrombosis, hemostasis and edema formation), Dr. Martin Halle (radiation vasculopathy) and Professor John Pernow (endothelial dysfunction).
External collaborations are carried out with Profs. Philip S. Tsao, Nicholas J. Leeper and Thomas Quertermous (all Stanford University, USA), Prof. Sonja Schrepfer (University Heart Center Hamburg, Germany), Dr. Jordan Miller (Mayo Clinic, USA), Prof. Kathryn Moore (New York University, USA), and Dr. Katey Rayner (Ottawa Heart Institute).
Investigations in Lars Maegdefessel’s lab are currently supported by the European Research Council (ERC StG NORVAS), the Swedish Heart-Lung Foundation, the Ragnar Söderberg Foundation, the Swedish Research Council (Vetenkapsrådet), the Cardiovascular Program (CVP) at Karolinska Institute (KI), the KI Foundation, and CERIC (Center of Excellence for Research in Inflammatory and Cardiovascular Diseases).
Awards and achievements
Prince Daniel Research Award 2014
Selected publications
Eken S, Jin H, Chernogubova E, Li Y, Simon N, Sun C, et al. MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions. Circ. Res. 2017 Feb;120(4):633-644.
Hartmann D, Fiedler J, Sonnenschein K, Just A, Pfanne A, Zimmer K, et al. MicroRNA-Based Therapy of GATA2-Deficient Vascular Disease. Circulation. 2016 Dec;134(24):1973-1990.
Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella F, et al. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat. Med. 2016 Oct;22(10):1140-1150.
Kojima Y, Volkmer J, McKenna K, Civelek M, Lusis A, Miller C, et al. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature. 2016 Aug 4;536(7614):86-90.
Wang D, Deuse T, Stubbendorff M, Chernogubova E, Erben R, Eken S, et al. Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis. Arterioscler. Thromb. Vasc. Biol. 2015 Sep;35(9):1945-53.
Maegdefessel L, Dalman R, Tsao P. Pathogenesis of abdominal aortic aneurysms: microRNAs, proteases, genetic associations. Annu. Rev. Med. 2014;65:49-62.
Maegdefessel L, Spin J, Raaz U, Eken S, Toh R, Azuma J, et al. miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development. Nat Commun. 2014 Oct 31;5:5214.
Deuse T, Hua X, Wang D, Maegdefessel L, Heeren J, Scheja L, et al. Dichloroacetate prevents restenosis in preclinical animal models of vessel injury. Nature. 2014 May;509(7502):641-4.
Maegdefessel L. The emerging role of microRNAs in cardiovascular disease. J. Intern. Med. 2014 Dec;276(6):633-44.
Maegdefessel L, Azuma J, Toh R, Deng A, Merk D, Raiesdana A, et al. MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion. Sci Transl Med 2012 Feb;4(122):122ra22.
Maegdefessel L, Azuma J, Toh R, Merk D, Deng A, Chin J, et al. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J. Clin. Invest. 2012 Feb;122(2):497-506.