Ignacio

Gonzalo Cancino

Assistant Professor


GONZALO.CANCINO@UMAYOR.CL


I obtained my BS in biology and PhD in Molecular and Cell biology both at P. Universidad Católica de Chile. Then, I moved to Canada to get my postdoctoral training with Drs. Freda Miller and David Kaplan at The Hospital for Sick Children-University of Toronto. Holding a Heart and Stroke Foundation of Canada and Becas Chile fellowships, I performed my postdoctoral training focusing in the molecular and cellular basis of neural development and adult neurogenesis.

My current research is focused in understand how the brain cortex develops. To study this, we analyze genes associated to neurodevelopmental disorders such as autism that are involved in embryonic neurogenesis and gliogenesis during brain cortical development. We also are interested in understanding how the p53 family contribute to neurodegeneration and synapsis.



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.

Project-a.jpg#asset:721. 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.
Project-b.jpg#asset:732. 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.
Project-c.jpg#asset:743. 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.
Project-d.jpg#asset:754. 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.

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

Jessica Molina

Research assistant

Biochemist from Universidad Austral de Chile. She performs behavioral experiments in the PTPRD conditional null mice.

Francisca Cornejo

Postdoctoral research fellow

Biochemist and PhD in Medical Sciences from Pontificia Universidad Católica de Chile. She is working on understanding how PTPRD regulates gliogenesis during embryonic brain development

Bastián Cortés

PhD student

Medical technologist from Universidad de Valparaíso. He is working on the role of PTPRD in embryonic neural stem cells during cortical brain development.

Begoña Aranda

PhD student

Begoña’s work focuses on understanding how the tyrosine kinase Abl regulates embryonic cortical development

Juan Ayala

Biotechnology student from Universidad Mayor. Studying the role of the tyrosine phosphatase PTPRD in adult neurogenesis

Beatriz Garate

Biotechnology student from Universidad Mayor. Beatriz work focuses on the role of c-Abl during cortical brain development

Fernando Soto

Biochemistry student from Universidad Andrés Bello. He is interested in understand how c-Abl regulates neurogenesis using the c-Abl conditional knockout

María Agustina Roccatagliata

Biotechnology student from Universidad Mayor. Agustina is interested in studying how the tyrosine kinase Abl regulates adult neurogenesis

Macarena Moya

Biotechnology student from Universidad Mayor. Macarena studies PTPRD functions in glial cells

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.