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From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study

Grant number: 17/25588-1
Support type:Research Projects - Thematic Grants
Duration: February 01, 2019 - January 31, 2024
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Daniel Martins-de-Souza
Grantee:Daniel Martins-de-Souza
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas, SP, Brazil
Assoc. researchers:Alessandro dos Santos Farias ; Andre Schwambach Vieira ; Andrea Schmitt ; Ary Gadelha de Alencar Araripe Neto ; Benilton de Sá Carvalho ; Emmanuel Dias-Neto ; Helder Takashi Imoto Nakaya ; Henrique Marques Barbosa de Souza ; Karina Diniz Oliveira ; Marcelo Alves da Silva Mori ; Marcus Bustamante Smolka ; Pedro Manoel Mendes de Moraes Vieira ; Peter Nilsson ; Rodrigo Affonseca Bressan ; Stevens Kastrup Rehen
Associated grant(s):19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class, AP.EMU
Associated scholarship(s):19/05747-3 - Maintaining and maturing oligodendrocyte cell line, BP.TT

Abstract

Schizophrenia is among the most disabling diseases of humankind, affecting 1% of the world's population (in Brazil, almost 2.5 million people are affected). One of the biggest hurdles faced by most patients is the poor efficacy of current antipsychotic medication. This stems from the lack of understanding of schizophrenia's pathobiology and the lack of biomarkers and biological mechanisms associated with a positive medication response. By employing state-of-the-art proteomics and lipidomics in blood plasma collected in vivo from patients before and after treatment, we aim to identify predictive biomarkers for medication response. These will be used to compose a mass spectrometry-based molecular assay to aid psychiatrists in predicting the likelihood of a successful treatment before initiating medication. This will be the first clinical test ever developed to determine medication response in psychiatry. Moreover, by analyzing the proteomes and lipidomes of these blood plasma samples, we can also better understand the biochemistry and biology involved the response. To develop new and more effective medication, we must increase our understanding of the molecular aspects of schizophrenia. Therefore, we will test several of the biological hypotheses our group has built over the past few years. For that, we are moving to a multidisciplinary approach employing CRISPR/Cas9, flow cytometry, proteomics, phosphoproteomics, lipidomics, interactomics, transcriptomics, and miRNA expression in coordination with several laboratories in Brazil and abroad to characterize postmortem brains and peripheral mononuclear blood cells from patients and mentally healthy controls. In addition, pre-clinical models will also be evaluated, such as induced pluripotent stem cell-derived neurons and glial cells, cerebral organoids, and cell lines of neurons, glia, and adipocytes. We will search for the validation of the key biological processes we found associated with schizophrenia such as tripartite synapses, spliceosomes, myelination, and energy pathway-associated alterations, as well as the role of the endocannabinoid system in glia. Results from these studies may point to biological processes that could be modulated by new drugs yet to be developed. Our results will lead to three major benefits in the field: 1) refining a biochemical assay able to predict the efficacy of medications currently available to patients, even before the treatment starts; 2) identifying key biochemical pathways associated with effective medication; 3) and better comprehension of schizophrenia's molecular basis and biochemistry, which is key for developing new treatments. Our project navigates from basic to applied science, towards the establishment of translational strategies driven by personalized and precision medicine concepts, helping to bring the bench closer to the bedside. (AU)

Scientific publications
(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)
SANTOS DE OLIVEIRA, PERCILLIA VICTORIA; GARCIA-ROSA, SHEILA; AZEVEDO SACHETTO, ANA TERESA; SOARES MORETTI, ANA IOCHABEL; DEBBAS, VICTOR; DE BESSA, TIPHANY CORALIE; SILVA, NATHALIA TENGUAN; PEREIRA, ALEXANDRE DA COSTA; MARTINS-DE-SOUZA, DANIEL; SANTORO, MARCELO LARAMI; MARTINS LAURINDO, FRANCISCO RAFAEL. Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes. REDOX BIOLOGY, v. 22, APR 2019. Web of Science Citations: 0.
BRANDAO-TELES, CAROLINE; DE ALMEIDA, VALERIA; CASSOLI, JULIANA S.; MARTINS-DE-SOUZA, DANIEL. Oligodendrocytes: Potential of Discovering New Treatment Targets. FRONTIERS IN PHARMACOLOGY, v. 10, MAR 5 2019. Web of Science Citations: 1.
AQUINO, ADRIANO; ALEXANDRINO, GUILHERME L.; GUEST, PAUL C.; AUGUSTO, FABIO; GOMES, ALEXANDRE F.; MURGU, MICHAEL; STEINER, JOHANN; MARTINS-DE-SOUZA, DANIEL. Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients. FRONTIERS IN PSYCHIATRY, v. 9, MAY 25 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
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