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
PER ERIKSSON TEAM
Molecular pathology of aortic aneurysm, allele-specific gene expression
The long-term interest of the Eriksson team is to investigate the underlying molecular mechanism of aortic aneurysm development. Aortic aneurysms are characterized by a degradation of the extra cellular matrix leading to a dilatation and eventually rupture of the vessel wall. The disease involves loss of elastin and remodeling of collagen, which are load bearing components of the vessel wall.
Major Research Focus
One of our main goals is to understand the underlying mechanism of the common aortopathy associated with a bicuspid aortic valve (BAV). BAV is the most common congenital disorder of the aortic valve and is present in 1-2 % of the population. The presence of a BAV predisposes for progressive dilatation of the ascending aorta and thereby constitutes an increased risk of aortic aneurysm that may eventually lead to fatal rupture or dissection of the aorta. The prevalence of aortic dilatation in patients with BAV has been estimated to be as high as 50-70%. As yet, the pathophysiologic basis for the increased risk of aortic complications associated with BAV is not known.
Currently, two major hypotheses have been proposed to explain the more fragile aorta in BAV patients. The first is that a developmental abnormality or a genetic predisposition in BAV results in structural weakness of the aorta, which renders it more susceptible to aortic complications. The second or ‘’hemodynamic’’ theory argues that the chronic exposure of ascending aortic wall to higher blood flow velocities and eccentric flow jets due to the geometry of a BAV lead to a higher propensity of the BAV aorta to aorthopathy. Recently, an increasing number of researchers agree that both factors may contribute to BAV related cardiac complications.
Our research team’s goal is to understand how different signaling pathways interact to bring about the similarities and differences in molecular events of aneurysm formation in patients with BAV and patients with a normal tricuspid aortic valve (TAV). Besides inherited properties, we also study the possible dysregulation of biological pathways due to abnormal hemodynamic stress, which may contribute and/or lay the foundation for more fragility in BAV aorta. In order to do so, we integrate the core molecular biology with genomic, genetic and bioinformatics analysis. Importantly, we have collected large and well characterized unique biobank, including tissue biopsies from dilated and non-dilated aorta in addition to DNA, plasma and serum samples. Candidate genes and pathways are initially identified by transcriptomics, proteomics, epigenomics and genetic analyses. Functional evaluations are performed using cell culture and in vitro analyses. RNA sequencing is used to study allele-specific gene expression.
Affiliated to the team is Lasse Folkersen, PhD, Technical University of Denmark.
The study on BAV associated aortopathy is a close collaboration with the group of Professor Anders Franco-Cereceda at the Cardiothoracic Surgery Unit at the Karolinska University Hospital Solna. Studies on abdominal aortic aneurysm are in collaborations with Docent Joy Roy and Docent Rebecka Hultgren at the Vascular Surgery group, Karolinska University Hospital Solna (http://ki.se/en/mmk/star-stockholm-aneurysm-research-group).
We are member of Leducq transatlantic network on BAV disease MIBAVA. The studies are supported by the Swedish Research Council and the Swedish Heart-Lung Foundation.