Mauricio Sáez, PhD.

Principal Investigator and Assistant Professor

Chromatin, Epigenetic, and Neuroscience Laboratory

PhD in Molecular and Cell Biology, Universidad Austral de Chile, Chile

mauricio.saez@umayor.cl

Líneas de Investigación

  • Modulación del Complejo Represivo Polycomb 2 en la maduración del sistema nervioso
  • Efecto modulador de Huntingtina en la actividad catalítica y localización genómica del Complejo Polycomb2, implicancias fisiológica y fisiopatológicas que ocurren durante el desarrollo de la enfermedad de Huntington.
  • Efecto de la reparación del DNA en la maduración del sistema nervioso y el efecto en trastornos del espectro autista.

Chromatin, Epigenetic and Neuroscience

Our research is focused on epigenetic mechanisms to control the chromatin´s structure and genes expression in the nervous system. We study the scarcely characterized function of Polycomb Repressive Complex 2 (PRC2) in the postmitotic cell, using the neuron as a model. PRC2 has been widely studied for set and maintain a repressive state of chromatin in the early stage of embryonic development and linage commitment, but its function in the postmitotic cells is poorly understood. To assess our objectives we combine chromatin immunoprecipitation with the last technologies of DNA sequencing to determine the role of PRC2 and their associated proteins in the control of chromatin beyond the traditional analysis on transcription start site. Specifically, we study the modulation of PRC2 by Huntingtin, a scaffold protein with ubiquitous expression and whose mutation is responsible for Huntington disease, a severe cognitive, motor a psychiatric disorder with fatal outcome. Understand the epigenetic alteration in this and other neurological disorders is the purpose of our team.

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Biography

Mauricio A. Sáez is Assistant Professor at Universidad Mayor and part of the Center for Genomics and Bioinformatics since January 2018. Mauricio is graduated in Biochemist at Universidad Austral de Chile, coursed his PhD in Molecular and Cellular Biology in the same University and completed his theses in CECS-Valdivia and the Hussman Institute of Human Genomics in Miami-Florida, studying the Rett Syndrome, a neurodevelopment disease by mutations in Methyl-CpG binding Protein 2 (MeCP2). Mauricio continued his studied in Rett Syndrome in his postdoctoral position in The Cancer Epigenetics and Biology Program at The Bellvitge Institute for Biomedical Research-Barcelona, realizing Exomes analysis to patients and families to identify and study new mutations responsible for Rett-like symptomatology. Back in, Chile Mauricio received a Postdoctoral Fondecyt award to study the function and target genes of the catalytic subunit of Polycomb Repressive Complex 2 in hippocampus. Recently, in 2017 Mauricio obtained an Initial Fondecyt Grant to study the modulation of Huntingtin on PRC2 function.

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Selected publications

Jorge-Torres OC, Szczesna K, Roa L, Casal C, Gonzalez-Somermeyer L, Soler M, Velasco CD, Martínez-San Segundo P, Petazzi P, Sáez MA, Delgado-Morales R, Fourcade S, Pujol A, Huertas D, Llobet A, Guil S, Esteller M. 2018. Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice. Cell Reports 23(6):1665-1677. CellPress. ISSN 2211-1247.

Lucariello M, Vidal E, Vidal S, Saez M, Roa L, Huertas D, Pineda M, Dalfó E, Dopazo J, Jurado P, Armstrong J, Esteller M. 2016. Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype. Human Genetics 135(12):1343-1354. Springer Berlin Heidelberg, ISSN: 0340-6717.

Aguilar R, Bustos FJ, Saez M, Rojas A, Allende ML, van Wijnen AJ, van Zundert B, Montecino M. Polycomb PRC2 complex mediates epigenetic silencing of a critical osteogenic master regulator in the hippocampus. 2016. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859(8): 1043-1055. Elsevier. ISSN: 1874-9399.

Sáez MA, Fernández-Rodríguez J, Moutinho C, Sanchez-Mut JV, Gomez A, Vidal E, Petazzi P, Szczesna K, Lopez-Serra P, Lucariello M, Lorden P, Delgado-Morales R, de la Caridad OJ, Huertas D, Gelpí JL, Orozco M, López-Doriga A, Milà M, Perez-Jurado LA, Pineda M, Armstrong J, Lázaro C, Esteller M. 2016. Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. Genetics in Medicine 8(4):378-85. Springer Nature. ISSN: 1098-3600.

Martínez de Paz A, Sanchez-Mut JV, Samitier-Martí M, Petazzi P, Sáez M, Szczesna K, Huertas D, Esteller M, Ausió J. 2015. Circadian cycle-dependent MeCP2 and brain chromatin changes. PLoS One 13;10(4):e0123693. PLOS. ISSN: 1932-6203.

Szczesna K, de la Caridad O, Petazzi P, Soler M, Roa L, Saez MA, Fourcade S, Pujol A, Artuch-Iriberri R, Molero-Luis M, Vidal A, Huertas D, Esteller M. 2014. Improvement of the Rett syndrome phenotype in a MeCP2 mouse model upon treatment with levodopa and a dopa-decarboxylase inhibitor. Neuropsychopharmacology 39(12):2846-56. Springer Nature. ISSN: 0893-133X.

Kerr B, Soto C J, Saez M, Abrams A, Walz K, Young JI*. 2012. Transgenic complementation of MeCP2 deficiency: phenotypic rescue of Mecp2-null mice by isoform-specific transgenes. European Journal of Human Genetics 20(1):69-76. Springer Nature. ISSN: 1018-4813.

Kerr B, Alvarez-Saavedra M, Sáez MA, Saona A, Young JI*. 2008. Defective body-weight regulation, motor control and abnormal social interactions in Mecp2 hypomorphic mice. Human Molecular Genetics 15;17(12):1707-17. Oxford University Press. ISSN 0964-6906.

Alvarez-Saavedra M, Sáez MA, Kang D, Zoghbi HY, Young JI*. Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. Human Molecular Genetics. 2007 Oct 1;16(19):2315-25. Oxford University Press. ISSN 0964-6906.

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