- Research office, John Bull Building, 16 Research Way, Derriford, Plymouth, PL6 8BU
Dr Jon Gil-Ranedo
Research Fellow in Cancer Stem Cell Neurobiology
Peninsula Medical School (Faculty of Health)
Research Fellow in Cancer Stem Cell Neurobiology, Peninsula Medical School, Faculty of Health, University of Plymouth.
I obtained my 5-years degree in Biochemistry in the University of the Basque Country, Spain, with an average grade of 9.18/10 (2001-2006). Then, I moved to the Autonomous University of Madrid and joined Prof. Marta Izquierdo gene therapy laboratory, at the Center for Molecular Biology “Severo Ochoa” (CBMSO). There, I achieved my PhD titled “Human glioblastoma-derived cancer stem cell characterization. Development of pre-clinic models and therapeutic approaches”, awarded Summa Cum Laude (2006-2010). I stayed at CBMSO as Postdoctoral Research Scientist in Prof. José Maria Almendral, and Dra Lourdes Ruíz Desviat and Dra Belén Pérez González labs (2010-2015). Finally, I moved to the Peninsula Medical School, University of Plymouth, where I joined as Research Fellow in Cancer Stem Cell Neurobiology at Claudia Barros lab (2015-present).
Member of the British Society for Developmental Biology
My broad scientific interest is biomedicine, from basic to translational, being particularly interested at the intersection of neural development with neoplastic transformation.
My PhD (2006-2010) focused on an evolving area of neuro-oncology which sheds new light onto cancer biology and provides key concepts that reconcile tumour biology and clinical outcome, the cancer stem cell (CSC) hypothesis. Very briefly, this hypothesis proposes that tumours can be regarded as “aberrant organs” initiated and supported by a population of CSCs. Like their tissue-specific counterparts, CSCs show an intrinsic refraction to conventional therapy due to their slow growth and inherent resistance to radio- and chemo-therapy.
Using high-grade brain tumour (glioblastoma, GBM) samples, I established and characterized stable cultures of CSC (named glioblastoma stem cells, GSCs), developing in vitro and in vivo preclinical GBM models that closely recapitulate the original tumour’s characteristics, allowing us to go beyond the limitations of traditional cancer models. Moreover, I challenged the models with different gene therapy strategies.
During my early postdoctoral stage (2010-2015) I studied the use of parvovirus as oncolytic agent, either alone or in combination with chemotherapeutic drugs, using my GSC-based GBM models. We described the restrictions imposed on the virus by the genetic and phenotypic heterogeneity of GSCs, focusing on p53 post-translational modifications. This work granted us two Spanish national and international patent applications on the treatment of human and animal glioblastoma using oncolytic virotherapy (ES2561906 and PCT/EP2019/086048).
In this later stage of my career (2015-present) I joined Claudia Barros laboratory at the Peninsula Medical School, University of Plymouth. Benefiting from the exceptional advantages of the post-embryonic Drosophila brain, and using a unique approach combining live single-cell transcriptomics and functional genetics with human tissue and stem cell cultures, we study neural stem cells (NSCs) during health and disease
I am increasing my expertise in neural development collaborating in projects aimed to decipher key factors for NSC reactivation, and to understand the spatio-temporal regulation of the molecular identity of different types of NSC. Currently, I am focused on the early events that drive the transformation of NSC into brain tumour stem cells. Our aim is to shed light on brain tumour initiation and development, and to identify and exploit potential therapeutic targets for these devastating tumours.
Gil-Ranedo J, Gallego-García C, Almendral JM. Viral targeting of glioblastoma stem cells with patient-specific genetic and post-translational p53 deregulations. Cell Reports (2021).
Gil-Ranedo J*, Gonzaga E*, Jaworek KJ, Berger C, Bossing T, Barros CS. STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation. Cell Reports (2019). (*Co-first authors).
Gil-Ranedo J, Hernando E, Valle N, Riolobos L, Maroto B, Almendral JM. Differential phosphorylation and n-terminal configuration of capsid subunits in parvovirus assembly and viral trafficking. Virology (2018).
Gil-Ranedo J*, Hernando E*, Riolobos L, Domínguez C, Kann M, Almendral JM. The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly. PLoS Pathogens (2015). (*Co-first authors).
Mendiburu-Eliçabe M, Gil-Ranedo J. Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts. Curr Cancer Drug Targets (2015).
Mendiburu-Eliçabe M*, Gil-Ranedo J*, Izquierdo M. Efficacy of rapamycin against glioblastoma cancer stem cells. Clin Transl Oncol (2014). (*Co-first authors).
Gil-Ranedo J, Mendiburu-Eliçabe M, García-Villanueva M, Medina D, del Álamo M, Izquierdo M. An off-target nucleostemin RNAi inhibits growth in human glioblastoma-derived cancer stem cells. PLoS One (2011).
Gil-Ranedo, J., Mendiburu-Eliçabe, M., Izquierdo, M. and Almendral, José M. Glioma-Parvovirus Interactions: Molecular Insights and Therapeutic Potential. Book: Novel Therapeutic Concepts in Targeting Glioma. Edited by Faris Farassati, Intech (2012).
International PCT application no. PCT/EP2019/086048 on the use of MVM strains and related parvoviruses in the treatment of cancers harboring mutations in the TP53 gene and/or post-translational modifications in the p53 protein, either alone or in combination with chemotherapeutic drugs (José M. Almendral, Carlos Gallego-García, and Jon Gil-Ranedo, co-inventors).