Laboratory of Molecular Sensors, CINV, University of Valparaiso
Principal Investigator: Dr Carlos González León
Postdoctoral Researcher, Fondecyt Project 3150634
Research Area: Biophysic of Connexin channels
PhD in Sciences, m/Neuroscience, University of Valparaíso (2014)
Medical Technologist, University of Chile (2007)
Bachellor in Science, University of Chile (2003)
Pasaje Harrington 287 Playa Ancha. Valparaíso, Chile.
I did the first steps of my scientific career in Dr Jaimovich´s Lab (Faculty of Medicine, University of Chile) where I was working on determine the role IP3R-mediated calcium signaling takes in early gene regulation on normal and Duchenne dystrophic skeletal muscle. Then, in 2010 I moved to Valparaiso and started my PhD training working in the fascinating connexin´s world in Dr Martínez´s Lab. The main research topic of Dr Martinez´s laboratory was sensorineural hearing loss produced by mutations in the GJB2 gene that encode for Cx26, a non-selective cationic pore-forming transmembrane protein, which is implicated in cell communication and cell homeostasis. It is quite intriguing that some mutations promote just deafness (named non-syndromic mutations) but other set of mutations produce deafness and extensive skin and corneal diseases (named syndromic mutations); however, the pathogenic mechanism of disease have been not conclusive. My PhD thesis was focused in to differentiate the/those pathogenic mechanisms that lead to non-syndromic and syndromic hearing loss. I discovered that syndromic mutants have altered oligomerization and form aberrant Heteromeric Hemichannels with Cx43 which plasma membrane expression leads to intracellular calcium overload and ATP release.
Currently I am running my Post-Doctoral project, whose main goal intends to unveil how the amino terminus of Cx26 and the water pocket are linked to regulate the voltage gating. I expected to go deep into the understanding of this process with emphasis in complete the picture of syndromic diseases from system biology to ultra structural insights, to fully understand how mutants compromise the channel function. Further, this knowledge will contribute development of pharmacological strategies.
1. García IE., Maripillán J., Ramachandran J., González C., Contreras JE., Martínez AD (2015) Syndromic deafness mutations in the amino terminus of Cx26 modify channel closure in heteromeric hemichannels. In preparation.
2. García IE., Contreras GF., Pupo A., Contreras JE., Latorre R., Martínez AD., González C (2015) Molecular determinants underlying the pathogenic mechanism promoted by the Cx26G12R KID syndromic mutation. In preparation.
3. García IE*., Escalona Y*., Martínez AD., Gonzalez C., Perez-Acle T (2015) Contribution of the amino terminal and water pocket constituents in determine the fast gating properties of Cx26 hemichannels. In preparation. *Equally contributed.
4. Bosen F., García IE., Pupo A., Willecke K., Martínez AD (2015) Pathological Mechanism of Keratitis Ichtiosis Deafness Syndrome (KID). In preparation.
5. García IE., Maripillán J., Jara O., Ceriani R., Palacios-Muñoz A., Ramachandran J., et al. (2015) Keratitis-Ichthyosis-Deafness Syndrome-Associated Cx26 Mutants Produce Nonfunctional Gap Junctions but Hyperactive Hemichannels When Co-Expressed With Wild Type Cx43. J Invest Dermatol. 135(5):1338-47 doi: 10.1038/jid.2015.20.