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Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics

Grant number: 13/08711-3
Support type:Research Grants - Young Investigators Grants
Duration: February 01, 2014 - July 31, 2018
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
Associated grant(s):14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC, AP.EMU
Associated scholarship(s):18/10362-0 - Evaluation of the effect of antipsychotics and the cannabidiol in an oligodendrocytes culture treated with cuprizone: implications for myelination, BP.MS
18/03422-7 - Identification of blood-based biomarkers for late-life depression through proteomics, BP.MS
17/25055-3 - The role of hnRNPs in oligodendrocytes and their implications on schizophrenia, BP.DR
+ associated scholarships 17/18242-1 - Biochemical pathways affected by cannabinoid drugs of human oligodendrocytes, BP.PD
16/18715-4 - Establishment of the hnRNPs role on schizophrenia through protein interaction network mapping, BP.PD
17/00025-4 - Establishment of selected reaction monitoring (SRM) technique for proteins of interest in schizophrenia, BP.IC
16/07948-8 - Relationship between a myelin-associated phosphodiesterase CNP and schizophrenia, BP.MS
16/04912-2 - Characterization of the mitochondrial proteome and oxidative biochemical profile of neural cells derived from iPSCs from patients with schizophrenia, BP.MS
16/07332-7 - The role of 14-3-3 and Ephrin signaling pathways on cellular communication between neurons-astrocytes and the functioning of the synapse tripartite, BP.DR
15/23049-0 - Employing human oligodendroglial cell cultures and glutamatergic dysfunction to understand the molecular basis of schizophrenia, BP.MS
15/09159-8 - Development of lipidomic platform to studies and their use in the assessment of response to antipsychotics in patients with schizophrenia, BP.PD
14/21035-0 - Quantitative proteomics in neural cell lines and organoids derived from induced pluripotent stem cells from schizophrenia patients, BP.PD
14/14881-1 - Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia, BP.PD
13/25702-8 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics, BP.JP - associated scholarships

Abstract

Schizophrenia is an incurable and debilitating mental disorder which affects approximately 1% of world population. It is a multifactorial disease involving exogenous and endogenous factors since the neurodevelopment. The molecular mechanisms of the disease are still to be unraveled for an integrated comprehension of the pathobiology. Additionally, biomarkers for diagnosis and for the likelihood of a successful treatment are not existent. Proteomics is, by definition, a suitable tool for investigating multifactorial disorders as schizophrenia. Proteins differentially expressed identified in a given biological condition may pinpoint which pathways are altered leading to a better comprehension of the disorder, and can be used as potential biomarker candidates. This project will perform a pioneer proteome analyses of plasma collected in vivo from patients and controls before and after medication. Our main goals are unraveling biochemical pathways modulated by the medication as well as revealing for the first time proteins that can act as potential biomarkers, which may indicate the likelihood of a successful treatment. Biomarker candidates will be combined in a mass spectrometry-based molecular assay to be evaluated as the first clinical test ever to determine medication response. Furthermore, we intend to contribute in the comprehension of the molecular aspects of schizophrenia. Based in our previous results, we will investigate the sub-proteomes of gray and white matter of four different brain regions from postmortem brains of schizophrenia patients and controls as well as preclinical models such as cultured oligodendrocytes. Our objective is to reveal differentially expressed proteins and their biochemical pathways for understanding their role in the establishment and maintenance of schizophrenia. This project will shed light in the comprehension of the molecular bases of schizophrenia and goes towards the development of a personalized medicine strategy with potential clinical implementation. (AU)

Articles published in Agência FAPESP about the research grant
Novel methodology increases resolution in oligodendrocyte proteomics 
Nova metodologia aumenta a resolução em análises de conjuntos de proteínas 
Study associates schizophrenia with defective processing of messenger RNA in cells 
New targets for treatment of schizophrenia 
Research paves the way for a new treatment against schizophrenia 
Articles published in Revista Pesquisa FAPESP about the project
Depression due to inflammation 
Filed patent(s) as a result of this research project

Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação BR1020170258521 - Universidade Estadual de Campinas (UNICAMP) . Solicitação em análise e dentro do prazo legal de sigilo previsto na legislação - November 2017, 30

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