Quantitative proteomics in neural cell lines and organoids derived from induced pluripotent stem cells from schizophrenia patients

• Grant number: 14/21035-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): May 01, 2015
• Effective date (End): April 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Juliana Minardi Nascimento
• Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics, AP.JP

Abstract

Understanding the complexity of some diseases is one of the greatest challenges currently facing medicine. Likewise for schizophrenia (SCZ), a multifactorial and severe psychiatric disorder, which may affect up to 1% of world population. The molecular mechanisms of schizophrenia are not yet fully elucidated, then invoking the use of appropriate scientific approaches to this end. Proteomics has emerged in the post-genomic era as a promising strategy to identify key targets and markers in the development and pathophysiology pathways of diseases. More recently, the emergence of induced pluripotent stem cell (iPSC) has enriched research on the understanding of human complex diseases, as a new and valuable tool that preserves the genetic diversity of donors, in addition to providing the ability to generate all cell types of an individual.Therefore, this project aims to combine neuroproteomics and iPSCs technology generated from schizophrenia patients and controls. The goal is to reveal groups of proteins that are differentially expressed in neural cells - progenitors, neurons and cerebral organoids (mini-brains) - generated from fibroblast of patients and healthy donors, aiming to characterize key-proteins implicated in this process.The study of schizophrenia cells derived directly from patients may lead to an integrated view of the expression of proteins during brain development, leading to the identification of biochemical pathways impaired. In addition, it will establish a platform for in vitro study of schizophrenia, with potential of control and manipulation of impaired pathways. Global analysis of protein expression during cell development stages may assist the search for new therapies targeting more personalized treatment of disease. (AU)

Scientific publications

(11)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DAKIC, VANJA; NASCIMENTO, JULIANA MINARDI; SARTORE, RAFAELA COSTA; MACIEL, RENATA DE MORAES; DE ARAUJO, DRAULIO B.; RIBEIRO, SIDARTA; MARTINS-DE-SOUZA, DANIEL; REHEN, STEVENS K. Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. SCIENTIFIC REPORTS, v. 7, OCT 9 2017. Web of Science Citations: 8.

ZUCCOLI, GIULIANA S.; SAIA-CEREDA, VERONICA M.; NASCIMENTO, JULIANA M.; MARTINS-DE-SOUZA, DANIEL. The Energy Metabolism Dysfunction in Psychiatric Disorders Postmortem Brains: Focus on Proteomic Evidence. FRONTIERS IN NEUROSCIENCE, v. 11, SEP 7 2017. Web of Science Citations: 6.

DEZONNE, ROMULO SPERDUTO; SARTORE, RAFAELA COSTA; NASCIMENTO, JULIANA MINARDI; SAIA-CEREDA, VERONICA M.; ROMAO, LUCIANA FERREIRA; ALVES-LEON, SONIZA VIEIRA; DE SOUZA, JORGE MARCONDES; MARTINS-DE-SOUZA, DANIEL; REHEN, STEVENS KASTRUP; ALCANTARA GOMES, FLVIA CARVALHO. Derivation of Functional Human Astrocytes from Cerebral Organoids. SCIENTIFIC REPORTS, v. 7, MAR 27 2017. Web of Science Citations: 12.

SAIA-CEREDA, VERONICA M.; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL; NASCIMENTO, JULIANA M. Psychiatric disorders biochemical pathways unraveled by human brain proteomics. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 267, n. 1, p. 3-17, FEB 2017. Web of Science Citations: 6.

GARCEZ, PATRICIA P.; NASCIMENTO, JULIANA MINARDI; DE VASCONCELOS, JANAINA MOTA; DA COSTA, RODRIGO MADEIRO; DELVECCHIO, RODRIGO; TRINDADE, PABLO; LOIOLA, ERICK CORREIA; HIGA, LUIZA M.; CASSOLI, JULIANA S.; VITORIA, GABRIELA; SEQUEIRA, PATRICIA C.; SOCHACKI, JAROSLAW; AGUIAR, RENATO S.; FUZII, HELLEN THAIS; BISPO DE FILIPPIS, ANA M.; GONCALVES VIANEZ JUNIOR, JOAO LIDIO DA SILVA; TANURI, AMILCAR; MARTINS-DE-SOUZA, DANIEL; REHEN, STEVENS K. Zika virus disrupts molecular fingerprinting of human neurospheres. SCIENTIFIC REPORTS, v. 7, JAN 23 2017. Web of Science Citations: 23.

SCHMITT, ANDREA; MARTINS-DE-SOUZA, DANIEL; AKBARIAN, SCHAHRAM; CASSOLI, JULIANA S.; EHRENREICH, HANNELORE; FISCHER, ANDRE; FONTEH, ALFRED; GATTAZ, WAGNER F.; GAWLIK, MICHAEL; GERLACH, MANFRED; GRUNBLATT, EDNA; HALENE, TOBIAS; HASAN, ALKOMIET; HASHIMOTO, KENIJ; KIM, YONG-KU; KIRCHNER, SOPHIE-KATHRIN; KORNHUBER, JOHANNES; KRAUS, THEO F. J.; MALCHOW, BEREND; NASCIMENTO, JULIANA M.; ROSSNER, MORITZ; SCHWARZ, MARKUS; STEINER, JOHANN; TALIB, LEDA; THIBAUT, FLORENCE; RIEDERER, PETER; FALKAI, PETER; FORCE, MEMBERS WFSBP TASK. Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia, part III: Molecular mechanisms. WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, v. 18, n. 5, p. 330-356, 2017. Web of Science Citations: 4.

DAKIC, VANJA; MACIER, RENATA DE MORAES; DRUMMOND, HANNAH; NASCIMENTO, JULIANA M.; TRINDADE, PABLO; REHEN, STEVENS K. Harmine stimulates proliferation of human neural progenitors. PeerJ, v. 4, DEC 6 2016. Web of Science Citations: 12.

NASCIMENTO, JULIANA M.; GARCIA, SHEILA; SAIA-CEREDA, VERONICA M.; SANTANA, ALINE G.; BRANDAO-TELES, CAROLINE; ZUCCOLI, GIULIANA S.; JUNQUEIRA, DANIELLE G.; REIS-DE-OLIVEIRA, GUILHERME; BALDASSO, PAULO A.; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL. Proteomics and molecular tools for unveiling missing links in the biochemical understanding of schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 12, SI, p. 1148-1158, DEC 2016. Web of Science Citations: 3.

GARCEZ, PATRICIA P.; LOIOLA, ERICK CORREIA; DA COSTA, RODRIGO MADEIRO; HIGA, LUIZA M.; TRINDADE, PABLO; DELVECCHIO, RODRIGO; NASCIMENTO, JULIANA MINARDI; BRINDEIRO, RODRIGO; TANURI, AMILCAR; REHEN, STEVENS K. Zika virus impairs growth in human neurospheres and brain organoids. Science, v. 352, n. 6287, p. 816-818, MAY 13 2016. Web of Science Citations: 388.

CASSOLI, JULIANA S.; IWATA, KEIKO; STEINER, JOHANN; GUEST, PAUL C.; TURCK, CHRISTOPH W.; NASCIMENTO, JULIANA M.; MARTINS-DE-SOUZA, DANIEL. Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 10, MAR 3 2016. Web of Science Citations: 13.

SAIA-CEREDA, VERONICA M.; CASSOLI, JULIANA S.; SCHMITT, ANDREA; FALKAI, PETER; NASCIMENTO, JULIANA M.; MARTINS-DE-SOUZA, DANIEL. Proteomics of the corpus callosum unravel pivotal players in the dysfunction of cell signaling, structure, and myelination in schizophrenia brains. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 265, n. 7, p. 601-612, OCT 2015. Web of Science Citations: 27.