Gonzalo Cancino

Profesor Asistente


Licenciado en ciencias biológicas de la Universidad Católica de Chile (UC). Luego obtuvo su doctorado en Biología Celular y Molecular (UC), estudiando el papel de la quinasa c-Abl en la enfermedad de Alzheimer, bajo la dirección de la Dra. Alejandra Álvarez. Posteriormente, realizó un postdoctorado en Neurodesarrollo y Neurogénesis Adulta en el laboratorio de Freda Miller y David Kaplan, The Hospital for Sick Children-University of Toronto, financiado por una beca de la Heart and Stroke Foundation of Canada y Becas Chile.

Su línea de investigación se centra en comprender cómo se desarrolla la corteza cerebral. Para esto, en su laboratorio estudian las bases celulares y moleculares del autismo, analizando genes asociados a enfermedades del neurodesarrollo como el autismo, que participen y regulen procesos de neurogénesis y gliogénesis embrionaria durante la formación de la corteza.


Gonzalo Cancino

PUBLICATIONS

Balboa, E., J. Castro, M.-J. Pinochet, G.I. Cancino, N. Matías, P. José Sáez, A. Martínez, A.R. Álvarez, C. Garcia-Ruiz, J.C. Fernandez-Checa, and S. Zanlungo. 2017. MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content. Redox Biol. 12. doi:10.1016/j.redox.2017.02.024.

Acuña, M., L. González-Hódar, L. Amigo, J. Castro, M.G. Morales, G.I. Cancino, A.K. Groen, J. Young, J.F. Miquel, and S. Zanlungo. 2016. Transgenic overexpression of Niemann-Pick C2 protein promotes cholesterol gallstone formation in mice. J. Hepatol. 64. doi:10.1016/j.jhep.2015.10.002.

Yuzwa, S.A., G. Yang, M.J. Borrett, G. Clarke, G.I. Cancino, S.K. Zahr, P.W. Zandstra, D.R. Kaplan, and F.D. Miller. 2016. Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks. Neuron. 91. doi:10.1016/j.neuron.2016.07.037.

Yang, G., G.I. Cancino, S.K. Zahr, A. Guskjolen, A. Voronova, D. Gallagher, P.W. Frankland, D.R. Kaplan, and F.D. Miller. 2016. A Glo1-Methylglyoxal Pathway that Is Perturbed in Maternal Diabetes Regulates Embryonic and Adult Neural Stem Cell Pools in Murine Offspring. Cell Rep. 17. doi:10.1016/j.celrep.2016.09.067.

Gouveia, A., K. Hsu, Y. Niibori, M. Seegobin, G.I. Cancino, L. He, F.E. Wondisford, S. Bennett, D. Lagace, P.W. Frankland, and J. Wang. 2016. The aPKC-CBP Pathway Regulates Adult Hippocampal Neurogenesis in an Age-Dependent Manner. Stem Cell Reports. 7. doi:10.1016/j.stemcr.2016.08.007.

Voronova, A., D. Gallagher, M. Zander, G. Cancino, A. Bramall, M.P. Krause, C. Abad, M. Tekin, P.M. Neilsen, D.F. Callen, S.W. Scherer, G.M. Keller, D.R. Kaplan, K. Walz, and F.D. Miller. 2015. Ankrd11 is a chromatin regulator involved in autism that is essential for neural development. Springerplus. 4. doi:10.1186/2193-1801-4-S1-L28.

Gallagher, D., A. Voronova, M.A. Zander, G.I. Cancino, A. Bramall, M.P. Krause, C. Abad, M. Tekin, P.M. Neilsen, D.F. Callen, S.W. Scherer, G.M. Keller, D.R. Kaplan, K. Walz, and F.D. Miller. 2015. Ankrd11 is a chromatin regulator involved in autism that is essential for neural development. Dev. Cell. 32. doi:10.1016/j.devcel.2014.11.031.

Gómez, A.V., G. Córdova, R. Munita, G.E. Parada, Á.P. Barrios, G.I. Cancino, A.R. Álvarez, and M.E. Andrés. 2015. Characterizing HSF1 binding and post-translational modifications of hsp70 promoter in cultured cortical neurons: Implications in the heat-shock response. PLoS One. 10. doi:10.1371/journal.pone.0129329.

Cancino, G.I., M.P. Fatt, F.D. Miller, and D.R. Kaplan. 2015. Conditional ablation of p63 indicates that it is essential for embryonic development of the central nervous system. Cell Cycle. 14. doi:10.1080/15384101.2015.1087618.

Zander, M.A., G.I. Cancino, T. Gridley, D.R. Kaplan, and F.D. Miller. 2014. The snail transcription factor regulates the numbers of neural precursor cells and newborn neurons throughout mammalian life. PLoS One. 9. doi:10.1371/journal.pone.0104767.

Fatt, M.P., G.I. Cancino, F.D. Miller, and D.R. Kaplan. 2014. P63 and p73 coordinate p53 function to determine the balance between survival, cell death, and senescence in adult neural precursor cells. Cell Death Differ. 21. doi:10.1038/cdd.2014.61.

Dixit, R., G. Wilkinson, G.I. Cancino, T. Shaker, L. Adnani, S. Li, D. Dennis, D. Kurrasch, J.A. Chan, E.C. Olson, D.R. Kaplan, C. Zimmer, and C. Schuurmans. 2014. Neurog1 and Neurog2 control two waves of neuronal differentiation in the piriform cortex. J. Neurosci. 34. doi:10.1523/JNEUROSCI.0614-13.2014.

Gallagher, D., A.A. Norman, C.L. Woodard, G. Yang, A. Gauthier-Fisher, M. Fujitani, J.P. Vessey, G.I. Cancino, N. Sachewsky, K. Woltjen, M.P. Fatt, C.M. Morshead, D.R. Kaplan, and F.D. Miller. 2013. Transient maternal IL-6 mediates long-lasting changes in neural stem cell pools by deregulating an endogenous self-renewal pathway. Cell Stem Cell. 13.

Cancino, G.I., F.D. Miller, and D.R. Kaplan. 2013. P73 haploinsufficiency causes tau hyperphosphorylation and tau kinase dysregulation in mouse models of aging and Alzheimer’s disease. Neurobiol. Aging. 34. doi:10.1016/j.neurobiolaging.2012.04.010.

Cancino, G.I., A.P. Yiu, M.P. Fatt, C.B. Dugani, E.R. Flores, P.W. Frankland, S.A. Josselyn, F.D. Miller, and D.R. Kaplan. 2013. p63 regulates adult neural precursor and newly born neuron survival to control hippocampal-dependent behavior. J. Neurosci. 33. doi:10.1523/JNEUROSCI.1251-13.2013.

Wang, J., D. Gallagher, L.M. Devito, G.I. Cancino, D. Tsui, L. He, G.M. Keller, P.W. Frankland, D.R. Kaplan, and F.D. Miller. 2012. Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell. 11. doi:10.1016/j.stem.2012.03.016.

Cancino, G.I., K. Perez de Arce, P.U. Castro, E.M. Toledo, R. von Bernhardi, and A.R. Alvarez. 2011. C-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice. Neurobiol. Aging. 32. doi:10.1016/j.neurobiolaging.2009.07.007.

Klein, A., M. Mosqueira, G. Martínez, F. Robledo, M. González, B. Caballero, G.I. Cancino, A.R. Alvarez, C. Hetz, and S. Zanlungo. 2011. Lack of activation of the unfolded protein response in mouse and cellular models of Niemann-Pick type C disease. Neurodegener. Dis. 8. doi:10.1159/000316540.

Fujitani, M., G.I. Cancino, C.B. Dugani, I.C.G. Weaver, A. Gauthier-Fisher, A. Paquin, T.W. Mak, M.J. Wojtowicz, F.D. Miller, and D.R. Kaplan. 2010. TAp73 acts via the bHLH Hey2 to promote long-term maintenance of neural precursors. Curr. Biol. 20. doi:10.1016/j.cub.2010.10.029.

Cancino, G.I., E.M. Toledo, N.R. Leal, D.E. Hernandez, L.F. Yévenes, N.C. Inestrosa, and A.R. Alvarez. 2008. STI571 prevents apoptosis, tau phosphorylation and behavioural impairments induced by Alzheimer’s β-amyloid deposits. Brain. 131. doi:10.1093/brain/awn125.

Alvarez, A.R., A. Klein, J. Castro, G.I. Cancino, J. Amigo, M. Mosqueira, L.M. Vargas, L.F. Yévenes, F.C. Bronfman, and S. Zanlungo. 2008. Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease. FASEB J. 22. doi:10.1096/fj.07-102715.

RESEARCH LINES

1. The cellular and molecular basis of autism

1. The cellular and molecular basis of autism

Autism is a neurodevelopmental disorder characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. Due to its strong genetic etiology, numerous animal models have been developed to help understanding the neuropathological basis of the behavioral manifestations observed in autistic-like animal models. However, it is not clear when and how these genetic alterations predisposed the brain to autism. It has been recently suggested that the neural stem cells might be important cellular substrates in autism, because alterations in genes associated to autism specifically in neural stem cells affect the number and type of neurons, disrupting neuronal circuitry and having long-lasting consequences in behavior and cognition. Then, in my laboratory we work with genes associated to autism that are involved in neurogenesis and gliogenesis to understand the molecular mechanism of brain cortex development.

2. The role of maternal environment during CNS development

2. The role of maternal environment during CNS development

The CNS development is influenced by environmental or external factors. For example, it has been demonstrated that alterations in maternal environment such as gestational diabetes and infections induce alterations in the number and differentiation of neural stem cells, which has been associated to several neurodevelopmental disorders such as autism and ADHD, however, their molecular mechanisms are still unknown. To understand this, my laboratory uses genetic models of diabetes and malnutrition models induced by high sugar or high fat diet to understand which are the molecular and cellular mechanisms associated to how the maternal environment regulates neural development.

3. Biology of lipids and neurodevelopment

3. Biology of lipids and neurodevelopment

Lipids are fundamental to the development and function of the CNS, however, how they regulate brain development and neural stem cell biology are poorly understood. To study how different types of lipids regulates neural development, in collaboration with Dr. Silvana Zanlungo (PUC), we use animal models of disorders associated to transport, synthesis and metabolism of cholesterol, sphingolipids and vitamin E, and we evaluate their impact in neural stem cell biology, and its consequences during brain cortical development.

4. Neurodegeneration and synaptic plasticity

4. Neurodegeneration and synaptic plasticity

Neurodegenerative diseases such as Alzheimer’s disease are characterized by progressive loss of synaptic connectivity, neurodegeneration and cognitive function. To understand the molecular basis of the neurodegenerative disorders, in collaboration with Dr. Alejandra Alvarez (PUC), we study the functions of the p53family members (p53, p63 and p73) during neurodegeneration and in synaptic plasticity. Using in vitro and in vivo approaches, we analyze how the p53 family regulates axonal growth, dendrogenesis and synaptogenesis.

PROJECTS

Name: FONDECYT Regular 1161374

Title: The impact of the tyrosine phosphatase PTPRD on neural stem cell biology and its contribution to autism spectrum disorder etiology.

Funding Institution: FONDECYT

Responsible Investigator: Gonzalo I. Cancino.

Period: 2016-2020

Name: IBRO

Title: Autism-associated genetic and environmental factors impacting brain development.

Funding Institution: IBRO

Responsible Investigator: Gonzalo I. Cancino.

Period: 2016

Name: CONICYT Redes 180113

Title: Modelling human brain disorders using iPSCs and brain organoids

Funding Institution: CONICYT

Responsible Investigator: Gonzalo I. Cancino.

Period: 2018-2019

Name: FONDECYT Postdoctorado 3190517

Title: The role of the ASD-associated gene PTPRD in gliogenesis during cortical brain development

Funding Institution: CONICYT

Responsible Investigator: Francisca Cornejo (Sponsor: Gonzalo I. Cancino)

Period: 2019-2023

TEAM

Jessica Molina
Asistente de investigación

Bioquímica de la Universidad Austral de Chile. Investiga las funciones de la tirosina fosfatasa PTPRD en el desarrollo del cerebro mediante estudios conductuales en el ratón nulo condicional para PTPRD.

Francisca Cornejo
Investigador Postdoctoral

Bioquímica y Doctora en Ciencias Médicas de la Pontificia Universidad Católica de Chile. Francisca está interesada en comprender como la tirosina fosfatasa PTPRD regula la gliogénesis durante el desarrollo de la corteza.

Bastián Cortés
Tesista de doctorado

Tecnólogo médico de la Universidad de Valparaíso. Bastián estudia las funciones de PTPRD en las células troncales neurales embrionarias durante el desarrollo de la corteza cerebral.

Begoña Aranda
Estudiante de doctorado

Licenciada en Bioquímica de la Universidad de Chile. El trabajo de Begoña está enfocado en comprender como la tirosina quinasa Abl regula el desarrollo embrionario de la corteza cerebral

Juan Ayala
Tesista de pregrado

Estudiante de Biotecnología de la Universidad Mayor. Estudiando el papel de la tirosina fosfatasa PTPRD en la neurogénesis adulta

Beatriz Garate

Tesista de pregrado

Estudiante de Biotecnología de la Universidad Mayor. Estudiando como c-Abl regula la neurogénesis embrionaria

Fernando Soto
Tesista de pregrado

Estudiante de Bioquímica de la Universidad Andrés Bello. Estudiando los mecanismos moleculares por los cuales la tirosina quinasa c-Abl regula la neurogénesis embrionaria

María Agustina Roccatagliata

Estudiante de Biotecnología de la Universidad Mayor. Agustina estudia como la tirosina quinasa Abl regula la neurogénesis adulta.

Macarena Moya

Estudiante de Biotecnología de la Universidad Mayor. Macarena estudia las funciones de PTPRD en células gliales

NETWORK

National

Dr. Alejandra Alvarez, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile.

Dr. Silvana Zanlungo, Facultad de Medicina, Pontificia Universidad Católica de Chile.

International


Dr. Freda Miller, The Hospital for Sick Children, Toronto, Canada.

Dr. David Kaplan, The Hospital for Sick Children, Toronto, Canada.

Dr. Greg Findlay, University of Dundee, Scotland.