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
ANDOR PIVARCSI GROUP
Skin cancer research
Skin cancer (excluding malignant melanoma and basal cell carcinoma) are the second most comon cancers among men and women in Sweden. Skin cancer is also the fastest growing cancer type, its incidence has nearly doubled in the last ten years. Cumulative exposure to ultraviolet light from the sun is the major risk factor and ultimate cause for most cases of skin cancers. Our research is about the understanding of the role of non-coding RNAs, RNAs that have regulatory functions in our cells, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in skin cancer. We study the role of ncRNAs in skin development, the maturation of skin cells, oncogenic transformation and also in their immune response, which has important roles in infection and cancer. We explore the interactions among ncRNAs and transcription factors as well as epigenetic changes in skin cancer. We hope that non-coing RNAs may become therapeutic targets and a novel way to treat skin cancers in the future.
Srivastava A, Nikamo P, Lohcharoenkal W, Li D, Meisgen F, Xu Landén N, Ståhle M, Pivarcsi A, Sonkoly E. MicroRNA-146a suppresses IL-17-mediated skin inflammation and is genetically associated with psoriasis. J Allergy Clin Immunol. 2017 Feb;139(2):550-561.
Lohcharoenkal W, Harada M, Lovén J, Meisgen F, Landén NX, Zhang L, Lapins J, Mahapatra KD, Shi H, Nissinen L, Kähäri VM, Ståhle M, Sonkoly E, Grandér D, Arsenian-Henriksson M, Pivarcsi A. MicroRNA-203 Inversely Correlates with Differentiation Grade, Targets c-MYC, and Functions as a Tumor Suppressor in cSCC. J Invest Dermatol. 2016 Dec;136(12):2485-2494.
Li D, Wang A, Liu X, Meisgen F, Grünler J, Botusan IR, Narayanan S, Erikci E, Li X, Blomqvist L, Du L, Pivarcsi A, Sonkoly E, Chowdhury K, Catrina SB, Ståhle M, Landén NX. MicroRNA-132 enhances transition from inflammation to proliferation during wound healing. J Clin Invest. 2015 Aug 3;125(8):3008-26.
Li D, Li X, Wang A, Meisgen F, Pivarcsi A, Sonkoly E, Ståhle M, Landén NX. MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration. J Invest Dermatol. 2015 Jun;135(6):1676-1685.
Pivarcsi A, Ståhle M, Sonkoly E. Genetic polymorphisms altering microRNA activity in psoriasis--a key to solve the puzzle of missing heritability? Exp Dermatol. 2014 Sep;23(9):620-4.
Villegas VE, Rahman MF, Fernandez-Barrena MG, Diao Y, Liapi E, Sonkoly E, Ståhle M, Pivarcsi A, Annaratone L, Sapino A, Ramírez Clavijo S, Bürglin TR, Shimokawa T, Ramachandran S, Kapranov P, Fernandez-Zapico ME, Zaphiropoulos PG. Identification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1. Mol Oncol. 2014 Jul;8(5):912-26.
Wang A, Landén NX, Meisgen F, Lohcharoenkal W, Ståhle M, Sonkoly E, Pivarcsi A. MicroRNA-31 is overexpressed in cutaneous squamous cell carcinoma and regulates cell motility and colony formation ability of tumor cells. PLoS One. 2014 Jul 28;9(7):e103206.
Meisgen F, Xu Landén N, Wang A, Réthi B, Bouez C, Zuccolo M, Gueniche A, Ståhle M, Sonkoly E, Breton L, Pivarcsi A. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J Invest Dermatol. 2014 Jul;134(7):1931-1940.
Gastaldi C, Bertero T, Xu N, Bourget-Ponzio I, Lebrigand K, Fourre S, Popa A, Cardot-Leccia N, Meneguzzi G, Sonkoly E, Pivarcsi A, Mari B, Barbry P, Ponzio G, Rezzonico R. miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma. Carcinogenesis. 2014 May;35(5):1110-20.
Meisgen F, Xu Landén N, Bouez C, Zuccolo M, Gueniche A, Ståhle M, Sonkoly E, Breton L, Pivarcsi A. Activation of toll-like receptors alters the microRNA expression profile of keratinocytes. Exp Dermatol. 2014 Apr;23(4):281-3.
Pivarcsi A, Meisgen F, Xu N, Ståhle M, Sonkoly E. Changes in the level of serum microRNAs in patients with psoriasis after antitumour necrosis factor-α therapy. Br J Dermatol. 2013 Sep;169(3):563-70.
Sääf A, Kockum I, Wahlgren CF, Xu N, Sonkoly E, Ståhle M, Nordenskjöld M, Bradley M, Pivarcsi A. Are BIC (miR-155) polymorphisms associated with eczema susceptibility? Acta Derm Venereol. 2013 May;93(3):366-7.
Wei TL, Xu N, Meisgen F, Stahle M, Sonkoly E, Pivarcsi A. Interleukin-8 is regulated by miR-203 at the posttranscriptional level in primary human keratinocytes. Eur J Dermatol. 2013 Apr 19 23; 66-71.
Bergman P, James T, Kular L, Ruhrmann S, Kramarova T, Kvist A, Supic G, Gillett A, Pivarcsi A, Jagodic M. Next-generation sequencing identifies microRNAs that associate with pathogenic autoimmune neuroinflammation in rats. J Immunol. 2013 Apr 15;190(8):4066-75.
Xu N, Meisgen F, Butler LM, Han G, Wang XJ, Söderberg-Nauclér C, Ståhle M, Pivarcsi A, Sonkoly E. MicroRNA-31 is overexpressed in psoriasis and modulates inflammatory cytokine and chemokine production in keratinocytes via targeting serine/threonine kinase 40. J Immunol. 2013 Jan 15;190(2):678-88.
Sääf A, Pivarcsi A, Winge MC, Wahlgren CF, Homey B, Nordenskjöld M, Tengvall-Linder M, Bradley M. Characterization of EGFR and ErbB2 expression in atopic dermatitis patients. Arch Dermatol Res. 2012 Dec;304(10):773-80.
Xu N, Zhang LY, Meisgen F, Harada M, Heilborn J, Homey B, Grander D, Stahle M, Sonkoly E, Pivarcsi A. MicroRNA-125b Down-regulates Matrix Metallopeptidase 13 and Inhibits Cutaneous Squamous Cell Carcinoma Cell Proliferation, Migration, and Invasion. J Biol Chem. 2012 Aug 24;287(35):29899-908.
Sonkoly E, Lovén J, Xu N, Meisgen F, Wei T, Brodin P, Jaks V, Kasper M, Shimokawa T, Harada M, Heilborn J, Hedblad MA, Hippe A, Grandér D, Homey B, Zaphiropoulos PG, Arsenian-Henriksson M, Ståhle M, Pivarcsi A. MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma. Oncogenesis. 2012 Mar 12;1:e3.
Fekete T, Szabo A, Beltrame L, Vivar N, Pivarcsi A, Lanyi A, Cavalieri D, Rajnavolgyi E, Rethi B. Constraints for monocyte-derived dendritic cell functions under inflammatory conditions. Eur J Immunol. 2012 Feb;42(2):458-69.