DANIEL MARTINS DE SOUZA
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
39 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 39
- Translational strategies to schizophrenia from a proteomic perspective(2012) MARTINS-DE-SOUZA, DanielThere is an urgent necessity of designing translational strategies to schizophrenia, a mental disorder that affects 30 million people worldwide. Proteomic studies have been providing data enough to pave the way for that, but these need to be connected in a concise manner in order to translate laboratorial findings to real improvements in the lives of the patients.
- Characterization of the human primary visual cortex and cerebellum proteomes using shotgun mass spectrometry-data-independent analyses(2012) MARTINS-DE-SOUZA, Daniel; GUEST, Paul C.; GUEST, Francesca L.; BAUDER, Corinna; RAHMOUNE, Hassan; PIETSCH, Sandra; ROEBER, Sigrum; KRETZSCHMAR, Hans; MANN, David; BABORIE, Atik; BAHN, SabineWe present the first characterization of the human occipital lobe (primary visual cortex) and cerebellum proteomes. Proteins were identified using a combination of gel electrophoresis and data-independent nanoflow liquid chromatography mass spectrometry (nLC-MSE). The resulting data sets comprised 391 and 330 unique proteins in occipital lobe and cerebellum, respectively, present in at least 75% of the analyzed samples with 297 proteins found in common. These proteins have been associated previously with conditions, such as neurological disorder, progressive motor neuropathy, Parkinson's disease and schizophrenia. The unique proteins identified in the occipital lobe included the interesting finding of growth hormone and several members of the Ca2+-dependent calmodulin kinase and serine/threonine protein phosphatase families. The complete mapping of these and other brain proteomes may help in the elucidation of neurological processes and identify potential targets for therapeutic strategies.
- S100B is downregulated in the nuclear proteome of schizophrenia corpus callosum(2014) STEINER, Johann; SCHMITT, Andrea; SCHROETER, Matthias L.; BOGERTS, Bernhard; FALKAI, Peter; TURCK, Christoph W.; MARTINS-DE-SOUZA, DanielHere we report the downregulation of S100B in the nuclear proteome of the corpus callosum from nine schizophrenia patients compared to seven mentally healthy controls. Our data have been obtained primarily by mass spectrometry and later confirmed by Western blot. This is an intriguing finding coming from a brain region which is essentially composed by white matter, considering the potential role of S100B in the control of oligodendrocyte maturation. This data reinforce the importance of oligodendrocytes in schizophrenia, shedding more light to its pathobiology.
- Characterization of the human serum depletome by label-free shotgun proteomics(2011) KOUTROUKIDES, Theodoros A.; GUEST, Paul C.; LEWEKE, F. Markus; BAILEY, David M. D.; RAHMOUNE, Hassan; BAHN, Sabine; MARTINS-DE-SOUZA, DanielWhile it is known that immunoaffinity depletion of abundant proteins in serum removes additional proteins beyond those targeted, there has been little characterization of the co-depleted proteins in the high abundant fraction, which we refer to here as the ""depletome''. We present evidence of co- depletion of non-targeted proteins in human serum using a top-20 immunodepletion column, as shown by label-free liquid chromatography mass spectrometry (LC-MS(E)) profiling. This led to identification of 147 proteins which were specific for this fraction and comprised proteins with functions predominantly in binding and transport of nucleotides, metal ions, carbohydrates and lipids. These results suggest that further studies on this commonly ignored serum fraction may provide new insights into clinical proteomics.
- Proteomics Tackling Schizophrenia as a Pathway Disorder(2012) MARTINS-DE-SOUZA, Daniel
- Differential proteome and phosphoproteome may impact cell signaling in the corpus callosum of schizophrenia patients(2016) SAIA-CEREDA, Veronica M.; CASSOLI, Juliana S.; SCHMITT, Andrea; FALKAI, Peter; MARTINS-DE-SOUZA, DanielSchizophrenia is a multifactorial disease in both clinical and molecular terms. Thus, depicting the molecular aspects of the disease will contribute to the understanding of its biochemical mechanisms and consequently may lead to the development of new treatment strategies. The protein phosphorylation/dephosphorylation switch acts as the main mechanism for regulating cellular signaling. Moreover, approximately onethird of human proteins are phosphorylable. Thus, identifying proteins differentially phosphorylated in schizophrenia postmortem brains may improve our understanding of the molecular basis of brain function in this disease. Hence, we quantified the phosphoproteome of corpus callosum samples collected post mortem from schizophrenia patients and healthy controls. We used state-of-the-art, bottom-up shotgun mass spectrometry in a two-dimensional liquid chromatography-tandemmass spectrometry setup in the MS Emode with label-free quantification. We identified 60,634 peptides, belonging to 3283 proteins. Of these, 68 proteins were differentially phosphorylated, and 56 were differentially expressed. These proteins are mostly involved in signaling pathways, such as ephrin B and ciliary neurotrophic factor signaling. The data presented here are novel because this was the very first phosphoproteome analysis of schizophrenia brains. They support the important role of glial cells, especially astrocytes, in schizophrenia and help to further the understanding of the molecular aspects of this disease. Our findings indicate a need for further studies on cell signaling, which might shape the development of treatment strategies.
article 78 Citação(ões) na Scopus Proteomics, metabolomics, and protein interactomics in the characterization of the molecular features of major depressive disorder(2014) MARTINS-DE-SOUZA, DanielOmics technologies emerged as complementary strategies to genomics in the attempt to understand human illnesses. In general, proteomics technologies emerged earlier than those of metabolomics for major depressive disorder (MDD) research, but both are driven by the identification of proteins and/or metabolites that can delineate a comprehensive characterization of MDD's molecular mechanisms, as well as lead to the identification of biomarker candidates of all types-prognosis, diagnosis, treatment, and patient stratification. Also, one can explore protein and metabolite interactomes in order to pinpoint additional molecules associated with the disease that had not been picked up initially. Here, results and methodological aspects of MDD research using proteomics, metabolomics, and protein interactomics are reviewed, focusing on human samples. (C) 2014, AICH - Servier Research Group- Proteomic approaches to unravel the complexity of schizophrenia(2012) MARTINS-DE-SOUZA, Daniel; GUEST, Paul C.; RAHMOUNE, Hassan; BAHN, SabineSchizophrenia is a debilitating mental disorder that affects approximately 30 million people worldwide. The development and progression of this disease is now thought to be precipitated through a complex interaction between altered gene function and environmental factors. Proteomic analyses have been applied extensively over the past 10 years in studies of several tissues from schizophrenic patients, resulting in increased insight into the affected molecular pathways. In addition, these proteomic approaches have led to the identification of a set of molecular biomarker assays as the first blood-based test to aid in the diagnosis of schizophrenia. Here, we discuss the main outcome of these investigations and suggest a practical means of integrating and translating the findings between the brain and peripheral blood to increase our understanding of schizophrenia pathophysiology.
- Differential expression of HINT1 in schizophrenia brain tissue(2012) VARADARAJULU, Jeeva; SCHMITT, Andrea; FALKAI, Peter; ALSAIF, Murtada; TURCK, Christoph W.; MARTINS-DE-SOUZA, DanielRecent findings in the literature suggest a relation between histidine triad nucleotide-binding protein-1 (HINT1) and psychiatric disorders such as major depression, anxiety, and schizophrenia, although its physiological roles are not completely comprehended. Using Western blot, we compared HINT1 protein expression in the postmortem dorsolateral prefrontal cortex and thalamus of schizophrenia patients and healthy controls for contributing to elucidate the role of HINT1 in schizophrenia pathophysiology. HINT1 was found to be downregulated in the dorsolateral prefrontal cortex and upregulated in the thalamus. Our results combined to previous studies in human samples and preclinical models support the notion that HINT1 must be more explored as a potential target for psychiatric disorders.
- PROTEOMIC TECHNOLOGIES FOR BIOMARKER STUDIES IN PSYCHIATRY: ADVANCES AND NEEDS(2011) MARTINS-DE-SOUZA, Daniel; GUEST, Paul C.; VANATTOU-SAIFOUDINE, Natacha; HARRIS, Laura W.; BOHN, SabineIn the postgenome era, proteomics has arisen as a promising tool for more complete comprehension of diseases and for biomarker discovery Some of these objectives have already been partly achieved for illnesses such as cancer. In the case of psychiatric conditions, however, proteomic advances have had a less profound impact. Here, we outline the necessity of improving and applying proteomic methods for biomarker discovery and validation in the field of psychiatric disorders. While proteomic-based applications in neurosciences have increased in accuracy and sensitivity over the past 10 years, the development of orthogonal validation technologies has fallen behind. These issues are discussed along with the importance of integrating systems biology approaches and combining proteomics with other research approaches. The future development of such technologies may put proteomics closer to clinical applications in psychiatry.