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JOY IROBI

J. Irobi is assistant professor Immunology/ Neurofunctional Genomics at the Faculty of Medicine and Life Sciences, Hasselt University since September 2016; and coordinator of the NGS activities within BIOMED. Her research previously focused on understanding the delicate balance between peripheral nerve homeostasis and degeneration. She showed that mutations in small heat-shock proteins HSPB1 and HSPB8 cause axonal degeneration and these chaperones have neuroprotective functions. Her current research focuses on chaperone mediated extracellular vesicle (EV or exosome) communications and identification of EV molecular signatures modulating neuroinflammation. One aspect centers on deciphering the neuroprotective mechanisms of extracellular HSPB1 and HSPB8 in transcellular EV signaling during neuroinflammation. By administering HSPBs loaded EV both in vitro and in vivo she is studying the protective activities of these EV in early and chronic inflammation. To study this, a wide variety of assays are applied including: density gradient, SEC, fluorescence NTA, flow cytometry, immunogold TEM and surface Plasmon resonance, RNA-NGS and proteomics analysis. BIOMED has access to well defined patient samples of multiple sclerosis (MS) through Universitaire Biobank Limburg. The second aspect focuses on vesicular biomarker development via miRNA sequencing of HSP-immunoisolation of plasma EV from MS patients. The (epi)genotype-phenotype correlations in MS phenotypic spectrum could identify unique EV-molecular signatures. The future applications of EV-heat shock proteins as a theragnostic tool including its use as biomarker for early prediction, assessing prognosis, monitoring of patient clinical outcomes and its potential as drug delivery vehicle for disease therapy.
 


Key Publications

  • Holmgren A, Bouhy D, De Winter V, Asselbergh B, Timmermans JP, Irobi J, Timmerman V. Charcot-Marie-Tooth causing HSPB1 mutations   increase Cdk5-mediated phosphorylation of neurofilaments. Acta Neuropathol. 2013 Jul;126(1):93-108. (I.F. 10.762).
  • Almeida-Souza L, Asselbergh B, d'Ydewalle C, Moonens K, Goethals S, de Winter V, Azmi A, Irobi J, Timmermans JP, Gevaert K, Remaut H, Van Den Bosch L, Timmerman V, Janssens S. J Neurosci. 2011 Oct 26;31(43):15320-8. Small heat-shock protein HSPB1 mutants stabilize microtubules in Charcot-Marie-Tooth neuropathy (I.F.: 7.271).
  • d'Ydewalle C, Krishnan J, Chiheb DM, Van Damme P, Irobi J, Kozikowski AP, Berghe PV, Timmerman V, Robberecht W, Van Den Bosch L. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. NATURE MEDICINE. 2011 Jul 24;17(8):968-74. (I.F.: 27.136).
  • Irobi J, Almeida-Souza L, Asselbergh B, De Winter V, Goethals S, Dierick I, Krishnan J, Timmermans JP, Robberecht W, De Jonghe P, Van Den Bosch L, Janssens S, Timmerman V. Mutant HSPB8 causes motor neuron specific neurite degeneration. HUM MOL GENET. 2010 Jun 10. (I.F.: 7.3860).
  • Dierick,I., Irobi,J., Janssens,S., Theuns,J., Lemmens,R., Jacobs,A., Corsmit,E., Hersmus,N., Van Den,B.L., Robberecht,W., De Jonghe,P., Van Broeckhoven,C., and Timmerman,V. Genetic variant in the HSPB1 promoter region impairs the HSP27 stress response. HUMAN MUTATION., 2007, 28, 830. (I.F.: 6.9).
  • Jordanova, A., Irobi, J., Thomas, F. P., Van Dijck, P., Meerschaert, K., Dewil, M., Dierick, I., Jacobs,A., De Vriendt, E., Van Gerwen, V., Guergueltcheva, V., Rao, C. V., Tournev, I., Gondim, F. A. A., D'hooghe, M., Callaerts, P., Van den Bosch, L., Timmermans, J.-P., Robberecht, W., Gettemans, J., Thevelein, J. M., De Jonghe, P., Kremensky, I., and Timmerman, V. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase associated with dominant intermediate Charcot-Marie- Tooth neuropathy. NATURE GENETICS 2006 Feb;38(2):197-202. Epub 2006 Jan 22. (I.F.: 26.494).
  • Kuhlenbäumer G, Hannibal MC, Nelis E, Schirmacher A, Verpoorten N, Meuleman J, Watts GD, De Vriendt E, Young P, Stögbauer F, Halfter H, Irobi J, Goossens D, Del-Favero J, Betz BG, Hor H, Kurlemann G, Bird TD, Airaksinen E, Mononen T, Serradell AP, Prats JM, Van Broeckhoven C, De Jonghe P, Timmerman V, Ringelstein EB, Chance PF. Mutations in SEPT9 cause hereditary neuralgic amyotrophy. NATURE GENETIC. Oct; 37(10):1044-6, Sep 25 (2005) (I.F.: 26.494).
  • Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kre-mensky I, Van Den Bosch L, Robberecht W, Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, Timmerman V. Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy. NATURE GENETICS (2004); 36, 597-601. (I.F.: 26.494).
  • Irobi,J., Van den Bergh,P., Merlini,L., Verellen,C., Van Maldergem,L., Dierick,I., Verpoorten,N., Jordanova,A., De Vriendt,E., Van Gerwen,V., Timmerman,V., De Jonghe,P.: The phenotype of motor neuropathies associated with BSCL2 mutations is broader than Silver syndrome and distal HMN type V. BRAIN (2004); 127(Pt 9): 2124-2130 (I.F.: 8.201).
  • Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Ver-poorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. NATURE GENETICS (2004); 36, 602-606 (I.F.: 26.494).

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