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.
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Contact: communication@cmm.se
CENTER FOR MOLECULAR MEDICINE
OLA NILSSON GROUP
Growth and Cartilage Biology
About
The skeleton provides support and protection to soft tissues and internal organs. It is crucial to our ability to move and it is also the body’s mineral storage and host for hematopoesis. Skeletal diseases comprise a varied group of disorders that affects the formation, growth, mineralization, and/or remodeling of the skeleton. In our research, we explore the cellular and molecular mechanisms of growth and skeletal disorders, and this knowledge is then applied to improve diagnosis and medical treatments of skeletal disorders as there for most of these diseases, are no or only imperfect treatments available.
Longitudinal bone growth occurs at the growth plate by a process called endochondral ossification in which cartilage is first formed and then remodeled into bone tissue. The growth plate is a layer of cartilage found near the ends of long bones, between the epiphysis and the metaphysis. The growth plate consists of three histologically and functionally discrete layers: 1) the resting zone. We previously demonstrated that the resting zone contains stem-like cells (unipotent stem cells, equivalent to stem cells in the skin and the intestines) which renew the pool of proliferative cells, 2) the proliferative zone, where chondrocytes actively proliferate and line up in columns, thereby directing growth primarily in one dimension, and 3) the hypertrophic zone, where the terminally differentiated chondrocytes calcify their matrix and attracts the invading bone and endothelial cells, a crucial step in endochondral bone formation.
Research
Our research in translational growth and skeletal disorders combine unique and well-characterized patient cohorts, advanced genetic and bioinformatic methods with genetic targeting in mice, cellular model systems and molecular biology methods. This research investigates the underlying molecular causes responsible for childhood growth and skeletal disorders. Ultimately, based on our data, we select specific genes or molecular mechanism that could be suitable targets for novel treatment strategies that will be tested in animals.
This research has immediate benefit for the patients suffering from genetic growth disorders as it will identify the underlying genetic diagnosis, thus enabling more accurate information about the cause, mode of inheritance, and prospects of improving their medical care. Understanding skeletal development, physiology, and pathology would offer novel treatment strategies for growth and skeletal diseases. It is highly important for several other large patient groups including children with inflammatory diseases and children treated for cancer who often develop growth problems.
Selected publications
Zhang Y, Zhao S, Hallgrimsdottir S, Zuo Y, Li X, Liu S, Lindelöf H, Wang S, Hammarsjö A, Batkovskyte D, Ye Y, Wang L, Yan Z, Lin J, Yu C, Chen z, Niu Y, Wang H, Zhao Z, Liu P, Qiu G, Posey JE, Wu Z, Lupski JR, Micule I, Anderlid BM, Voss U, Sulander D, Kuchinskaya E, Nilsson O, Zhang TJ, Grigelioniene G, Wu N. Expanding the mutation and phenotype spectrum of MYH3-related skeletal disorders. NPJ Genom Med. 2022 Feb 15;7(1):11.
Lennartson O, Lodefalk M, Wethje H, Stattin EL, Sävendahl L, Nilsson O. Bilateral epiphysiodesis due to extreme tall stature in a girl with a de novo DNMT3A variant associated with Tatton-Brown-Rahman syndrome. Front Endocrinol (Lausanne). 2021 Oct 13;12:752756.
Dou Z, Muder D, Baroncelli M, Bendre A, Gkourogianni A, Ottosson L, Vedung T, Nilsson O. Rat perichondrium transplanted to articular cartilage defects forms articular-like, hyaline cartilage. Bone. 2021 Jun 8;151:116035. doi: 10.1016/j.bone.2021.116035.
Dou Z, Chau M, Muder D, Vedung T, Nilsson O. Optimized protocols for in situ hybridization, immunohistochemistry, and immunofluorescence on skeletal tissue. Acta Histochem 2021 Jun 30;123(5):151747.
Gkourogianni A, Andrade AC, Segerlund E, Werner-Sperker A, Jonsson BA, Horemuzova E, Dahlgren J, Burstedt M, Nilsson O. Pre and postnatal growth failure with microcephaly due to two novel heterozygous IGF1R mutations and response to growth hormone treatment. Acta Paediatr. 2020 Oct;109(10):2067-2074.
Nilsson O. Aggrecanopathies highlight the need for genetic evaluation of selected ISS children: Commentary on “High frequency of pathogenic ACAN variants including an intragenic deletion in selected individuals with short stature.” Invited commentary. Eur J Endocrinol. 2020Aug;183(2):C9-C10.
Imel EA, Glorieux FH, Whyte MP, Munns CF, Ward L, Nilsson O, Simmons JH, Padidela R, Namba N, Cheong HI, Pitukcheewanont P, Sochett E, Högler W, Muroya K, Tanaka H, Gottesman GS, Biggin A, Perwad F, Mao M, Chen CY, Skrinar A, San Martin J, Portale AA. Burosumab vs. continuation of conventional therapy in children with X-linked hypo-phosphatemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019 Jun 15;393(10189):2416-2427.
Jee YH, Baron J, Nilsson O. New developments in the genetic diagnosis of short stature. Curr Opin Pediatr. 2018 Aug;30(4):541-547.
Lui JC, Barnes KM, Dong L, Yue S, Graber E, Rapaport R, Dauber A, Nilsson O, Baron J. Ezh2 mutations found in the Weaver overgrowth syndrome cause a partial loss of H3K27 histone methyltransferase activity. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1470-1478.
Gkourogiannin A, Andrew M, Tyzinski L, Crocker M, Douglas J, Dunbar N, Fairchild J, Funari MF, Heath KE, Jorge AA, Kurtzman T, LaFranchi S, Lalani S, Lebl J, Lin Y, Los E, Newbern D, Nowak C, Olson M, Popovic J, Průhová Š, Elblova L, Quintos JB, Segerlund E, Sentchordi L, Shinawi M, Stattin EL, Swartz J, Ariadna GA, Sinhué DC, Hosono H, Sanchez-Lara PA, Hwa V, #, Dauber A#. Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations. #Contributed equally. J Clin Endocrinol Metab. 2017 Feb 1;102(2):460-469.
Lui JC, Garrison P, Nguyen Q, Ad M, Keembiyehetty C, Chen W, Jee YH, Landman E, Nilsson O, Barnes KM, Baron J. Histone methyltransferases EZH1 and 2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy. Nature Commun. 2016 Nov 29;7:13685.
Baron J, Sävendahl L, De Luca F, Dauber A, Phillip M, Wit JM, Nilsson O. Short and tall stature: a new paradigm emerges. Nat Rev Endocrinol. 2015 Dec;11(12):735-46.
Nilsson O, Guo M, Dunbar N, Popovic J, Flynn D, Jacobsen C, Lui JC, Hirschhorn JN, Baron J, Dauber A. Short stature, accelerated bone maturation, and early growth cessation due to heterozygous aggrecan mutations. J Clin Endocrinol Metab. 2014 Aug;99(8):E1510-8.
Lui JC, Nilsson O, Chan Y, Palmer CD, Andrade AC, Hirschhorn JN, Baron J. Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height. Hum Mol Genet 2012 Dec 1;21(23):5193-5201.
Julian C. K. Lui, Anenisia C. Andrade, Anita Hegde, WeiPing Chen, Jeffrey Baron, Ola Nilsson. Spatial and Temporal Regulation of Gene Expression in the Mammalian Growth Plate. Bone. 2010 May;46(5):1380-90.