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
MAGDALENA PAOLINO TEAM
Ubiquitination in health and disease
Our research aims to unveil the diverse roles of ubiquitination in preventing or driving diseases. Ubiquitination is an essential post-translational protein modification required to maintain cellular homeostasis, and alterations in ubiquitin-dependent pathways have been implicated in the pathogenesis of several human diseases. However, ubiquitination is a highly complex process and various aspects of the ubiquitin system are not yet fully understood. Gaining insight into the cellular and molecular mechanisms of ubiquitination, as well as into its physiological roles is therefore critical on the path to designing novel treatments. Our team applies innovative techniques to model diseases and alter the functions of ubiquitin-related genes in order to reveal the underlying molecular basis of disease pathogenesis, primarily focusing on cancer, immunity and metabolism. Our ultimate aim is to provide novel opportunities for the development of more effective and specific therapeutic strategies.
Gavali S, Liu J, Li X, Paolino M. Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.
Int J Mol Sci 2021, 22(19), 10800
Paolino M, Koglgruber R, Cronin SJF, Uribesalgo I, Rauscher E, Harreiter J, et al.
RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature 2021 Jan;589(7842):442-447
Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, et al.
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.
Nature 2018 11;563(7732):564-568
Suriben R, Kaihara K, Paolino M, Reichelt M, Kummerfeld S, Modrusan Z, Dugger DL, Newton K, Sagolla M, Webster JD, Liu J, Hebrok M, Dixit VM. β-cell insulin secretion requires the ubiquitin ligase COP1. Cell 2015. 163 (6), 1457-1467.
Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C, Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G, Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 2014. 507 (7493), 508-512.
Paolino M, Thien CB, Gruber T, Hinterleitner R, Baier G, Langdon WY, Penninger JM. Essential role of E3 ubiquitin ligase activity in Cbl-b-regulated T cell functions. J Immunol. 2011, 186 (4), 2138-2147.