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Projects. Life and Matter Sciences

Directed neuronal differentiation of stem-like glioma initiating cells

Lead Researcher:
Núria de la Iglesia Zaragoza

Research Centre:
Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS). Barcelona.


Núria de la Iglesia ZaragozaGliomas are one of the most aggressive tumours in humans. They have a subpopulation of tumoral cells that present "stem-like" properties, such as auto-renovation, pluripotentiality and the ability to recapitulate the original tumour through transplant into a healthy host. These cells, known as Glioma Initiating Cells (GIC) share characteristics with normal neural stem cells, which are able to generate the three main cell types of the central nervous system: neurons, astrocytes and oligodendrocytes. This finding has opened the doors to new therapies specifically targeting GIC, given that these cells may be responsible for the recurrence of the tumour after conventional anti-cancer treatments. These newly emerging treatments include pro-differentiating therapies, which stimulate the differentiation of stem-like GIC, thereby depriving them of their tumorigenic properties. This study aims to apply a differentiating pro-neuronal therapy to gliomas, while taking it a step further. It proposes not only to promote the neuronal differentiation of GIC to induce a state of post-mitotic differentiation, but also to sensitize these glioma initiating cells to spontaneous apoptosis, taking advantage of the mutational profile of the tumour itself.

Throughout 2012, a collection of GIC cell-lines was obtained, and these have been classified according to their expression of Ink4a/Arf tumoral suppressors. This classification makes it possible to predict which type of GIC will respond better to pro-neuronal therapy. In turn, lentivirus was obtained to generate GIC lines that inducibly express pro-neural genes (Ngn1, NeuroD1, etc.). The first experiments with neuronal differentiation induction in culture are now under way.


Researcher's web address:


Núria de la Iglesia Zaragoza

Dr. Núria de la Iglesia studied for her doctoral thesis in the Biochemistry and Molecular Biology Department of the University of Barcelona, under the direction of Dr. Joan J. Guinovart and Dr. Joan Carles Ferrer (1997-2001). After this, Dr. de la Iglesia joined the laboratory of Dr. Azad Bonni in Harvard Medical School for her post-doctoral training (2002-2008). During this time her main contribution was in the field of gliomas by studying the role of STAT3, a pleiotropic transcription factor which promotes astrocytic differentiation but also shows oncogenic behaviour in several solid tumours. Dr de la Iglesia proved that STAT3 plays a pro-oncogenic role or acts as a tumour suppressor, depending on the mutational profile of the tumour. While STAT3 acts as a tumour suppressor in the context of the PTEN route, this transcription factor is necessary for transformation mediated by mutant EGFRvIII (de la Iglesia, N. et al., Genes Dev 22, 449-62 (2008); de la Iglesia, N. et al., J Neurosci 28, 5870-8 (2008)). Dr de la Iglesia also collaborated in other studies on oxidative stress and neuronal apoptosis (Lehtinen, M.K. et al., Cell 125, 987-1001 (2006)), neuronal morphology (Gaudilliere, B. et al., Neurone 41, 229-41 (2004); Yang, Y. et al., Science 326, 575-8 (2009)) and the differentiation of neural stem cells, acquiring solid experience in the field of developmental neurobiology.

In 2009, Dr de la Iglesia joined the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) as a Ramón y Cajal researcher, where she leads the emerging group for Gliomas and Neural Stem Cells, focused on the application of her developmental neurobiological knowledge to the study of the molecular mechanisms causing the onset, permanence and invasion of gliomas.

*All intellectual property rights belong to the author. Reproduction of all or part of the work without permission from the author is prohibited. © RAMÓN ARECES FOUNDATION. All rights reserved. 

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