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BIOMED

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JOY IROBI - NEUROFUNCTIONAL GENOMICS LAB

"PROMOTING NEUROREGENERATION USING MODIFIED EXTRACELLULAR VESICLES AS NANOTHERAPEUTICS"

 


We are interested in the use of modified exosomes or extracellular vesicles (EV) as a next generation repair delivery cargo in the nervous system. EV are specialized nanosized vesicles released by many cell types with different biological effects. We are interested in mechanisms of how EV communications regulate protein homeostasis or ‘proteostasis’ pathways in multiple sclerosis (MS) disease. The development of engineered EV-based nanotherapy and nanomedicine for treating MS is lacking. The delivery of therapeutic targets via EV is an innovative approach in MS treatment, and could be developed to focus on both anti-inflammation and the stimulation of CNS repair.

To combat chronic neuroinflammation and the associated cellular stress response, we concentrate on small molecular chaperone mediated EV communications. This allows us to understand the mechanisms and biological processes that lead to disease and to identify potential anti-inflammatory biomarkers enriched in the modified EV cargos. To study these processes, we evaluate the effects of modified EV in human neural and immune cells, MS samples and in experimental MS mouse models using various functional genomics, molecular biology and neuroimmunology techniques.

Although we have many hurdles to overcome, owing to the heterogeneity of EV populations, future clinical translation of engineered EV as nanomedicine may change the strategy used in treating neurodegenerative diseases.

 

Currently we are working on:

  • Bioreactor 3D-cell culture, EV mass production and detailed characterization of modified EV.
  • Defining modified EV disease limiting activities in neural, immune cells and tissues.
  • Determining the activities of modified EV in MS patient lymphoid cells.
  • In vivo characterization of modified EV nanotherapeutic activities by using MS mouse models.
  • 3D Fibercell Hollow Fiber bioreactor cell culture system
  • Isolation, purification and characterization of extracellular vesicles

  • RNA and Peptide sequencing analysis of extracellular vesicles

  • Targeted RNA sequencing of human Inflammation and immunity transcriptome gene panel

  • Organotypic brain slice cultures- ex vivo model of remyelination

  • Experimental autoimmune encephalomyelitis (EAE): mouse model of CNS inflammation

  • Cuprizone model: mouse model of de- and remyelination

Bram van den Broek, PhD student (PhD supervisor)

Project title: Molecular mechanism of small heat shock proteins in extracellular vesicles


Britt Van de Haterd, candidate PhD student (PhD supervisor).

Project title: Engineered oligodendroglia cell-derived extracellular vesicles as nanotherapeutics for multiple sclerosis.


 

  1. Bouhy D, Juneja M, Katona I, Holmgren A, Asselbergh B, De Winter V, Hochepied T, Goossens S, Haigh JJ, Libert C, Ceuterick-de Groote C, Irobi J, Weis J, Timmerman V. A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant HSPB8. Acta Neuropathol. 2018 Jan;135(1):131-148. IF: 18.174

  2. d'Ydewalle C, Krishnan J, Chiheb DM, Van Damme P, Irobi J, Kozikowski AP, Vanden Berghe P, 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 Med. 2011 Jul 24;17(8):968-74. IF: 30.357

  3. Irobi J, Almeida-Souza L, Asselbergh B, De Winter V, Goethals S, Dierick I, Krishnan J, Timmermans JP, Robberecht W, DeJonghe P, Van Den Bosch L, Janssens S, Timmerman V. Mutant HSPB8 causes motor neuron-specific neurite degeneration. Hum Mol Genet. 2010 Aug 15;19(16):3254-65. IF: 7.636

  4. 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, Kremensky I, Van Den Bosch L, Robberecht W, Van 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 Genet. 2004 Jun;36(6):597-601. IF: 31.616

  5. Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten 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. Nature Genet. 2004 Jun;36(6):602-6. IF: 31.616