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
CAROLINA HAGBERG GROUP
Adipose tissue nutrient uptake and metabolism
The Hagberg group integrates vascular biology with nutrient biochemistry to study how our adipose tissue handles overnutrition, asking why weight gain leads to cardiometabolic diseases in some, but not all, obese individuals. Our goal is to identify early pathological mechanisms that can be used clinically to prevent or reverse the emergence of obesity-associated diseases, which would improve both patient care and life quality.
Our research is focused on human adipocytes that we study using clinical biopsies and unique in vitro culture models, subsequently using research animals to mechanistically validate our findings in vivo. Current projects focus on the regulatory role of the vascular endothelium, on deciphering how cholesterol loading impacts adipose tissue function and on the metabolic demands of cell growth. We are a young, dynamic research group located at the 8th floor of the brand-new research building BioClinicum, working there within the stimulating environment of the Cardiovascular Medicine research division, with numerous possibilities for numerous interesting collaborations.
Originally from Helsinki, Finland, Carolina did her PhD with Ulf Eriksson at MBB, Karolinska Institutet (KI) studying the metabolic role of the vascular growth factor VEGF-B, which was published in two consecutive Nature papers (Hagberg et al, 2010 & 2012). She then went on for a postdoctoral visit to EPFL in Switzerland in the laboratory of Profs. Auwerx and Schoonjans to study energy metabolism and mitochondrial function. Returning to KI she then joined the lab of Kirsty Spalding at ICMC at KI Huddinge to study human adipose tissue and its role in metabolic disease, finding that mature adipocytes endoreplicate during obesity and in response to chronic insulin stimulation can become senescent (Li & Hagberg et al, in press in Nature Medicine 2021). She also was involved in developing novel methods to study mature adipocytes, a notoriously difficult cell type to study due to their high lipid content (Hagberg et al, Cell reports 2018).
In 2019 after receiving a KI faculty-funded position as Assistant Professor she set up her own lab, relocating to CMM and the Cardiovascular Medicine division at the Department of Medicine Solna where she now heads a team of four people. In 2019 she also received a VR Starting Grant, and she has been awarded numerous other research grants such Åke Wiberg, Jeanssons Stiftelser and KI KID funding. The lab has just published their first paper, describing HUVAS, human unilocular vascularized adipocyte spheroids, as a novel model to study human adipose tissue development and hypertrophy (Ioannidou et al, in press in Journal of Physiology, 2021).
Ioannidou A*, Altar S*, Schipper R, Baganha F, Åhlander M, Hornell A, Fisher R, Hagberg CE. Hypertrophied human adipocyte spheroids as in vitro model of weight gain and adipose tissue dysfunction. Journal of Physiology, online ahead of print, Aug (2021), (*equal contribution)
Li Q*, Hagberg CE*, Silva Cascales H, Lang S, Hyvönen MT, Salehzadeh F, Chen P, Alexandersson I, Terezaki E, Harms MJ, Kutschke M, Arifen N, Krämer N, Aouadi M, Knibbe C, Boucher J, Thorell A, Spalding KL. Hyperinsulinemia drives human adipocytes to re-enter cell cycle and senesce. In press in Nature Medicine (*equal contribution)
Harms MJ, Li Q, Lee S, Zhang C, Kull B, Hallen S, Thorell A, Alexandersson I, Hagberg CE, Peng XR, Mardinoglu A, Spalding KL, Boucher J. Mature human adipocytes cultured under permeable membranes maintain identity, function, and can transdifferentiate into brown-like adipocytes. Cell Reports 27(1):213-225 (2019)
Hagberg CE#, Li Q, Kutschke M, Bhowmick D, Kiss E, Shabalina IG, Harms MJ, Shilkova O, Kozina V, Nedergaard J, Boucher J, Thorell A, Spalding KL. Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and Cellular Heterogeneity. Cell Reports 24(10):2746-2756 (2018) #Corresponding author
Abreu-Vieira G, Hagberg CE, Spalding KL, Cannon B, Nedergaard J. Adrenergically-stimulated blood flow in brown adipose tissue is not dependent on thermogenesis. Am J Physiol Endocrinol Metab. 308: E822–E829 (2015)
Pirinen E, Canto C, Jo YS, Morato L, Zhang H, Menzies KJ, Williams EG, Mouchiroud L, Moullan N, Hagberg C, Li W, Timmers S, Imhof R, Verbeek J, Pujol A, Van Loon B, Viscomi C, Zeviani M, Schrauwen P, Sauve Aa, Schoonjans K, Auwerx J. Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle. Cell Metabolism 19;6 1034-41 (2014)
Hagberg C*, Mehlem A*, Falkevall A, Muhl L, Eriksson U. Endothelial fatty acid transport: role of vascular endothelial growth factor B. Physiology 28;2 125-34 (2013) (*equal contribution)
Hagberg CE*, Mehlem A*, Falkevall A, Muhl L, Fam BC, Ortsater H, Scotney P, Nyqvist D, Samen E, Lu L, Stone-Elander S, Proietto J, Andrikopoulos S, Sjoholm A, Nash A, Eriksson U. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature 490;7420 426-30 (2012) (*equal contribution)
Hagberg CE, Falkevall A, Wang X, Larsson E, Huusko J, Nilsson I, van Meeteren LA, Samen E, Lu L, Vanwildemeersch M, Klar J, Genove G, Pietras K, Stone-Elander S, Claesson-Welsh L, Yla-Herttuala S, Lindahl P, Eriksson U. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464;7290 917-U136 (2010)