Lider (es): Jose Cesar Rosa
Telefone (s): (16) 2101-9366
Linha de pesquisa
Biologia Celular e Molecular de Cancer
Linhas gerais/General outline
Cancer proteomics. Discovery of new biomarkers and new drugs for the treatment of brain cancer. Using state of the art mass spectrometry strategies and cellular and molecular biology assays. Advanced analysis in posttranslational modification (phosphorylation, glycosylation, etc.). Bioinformatics applied to proteomics.
Linhas de pesquisa/Research areas
1) Biomarker discovery in cancer using mass spectrometry-based proteomics.
Our group is interested in the development of functional and structural proteomics of cancer and stem cells. An elaborate gene network is regulated during the control of cell proliferation and differentiation. We focus our research on the products of these genes, the proteins, by studying their differential expression, localization, and interaction with other proteins, since they represent a shortcut between the genome and the development of diseases such as cancer. We also aim to understand the biology of stem cells during self-replenishment and comprehend processes leading to the differentiation of these cells into other cell types. To develop our research, we employ methodologies for the separation of proteins and peptides, namely liquid chromatography, affinity chromatography, and electrophoresis. We identify the protein entities and post-translation alterations (phosphorylation and glycosylation) by mass spectrometry (ESI-MS/MS and MALDI-TOF/TOF). Our major projects involve samples of tumors and clinically relevant cells in glioma (astrocytoma, oligodendroglioma e meduloblastoma), and our main objective is to identify proteins/genes that may serve as disease markers for the diagnosis, prognosis, and potential therapeutic target.
2) Functional proteomics: mechanisms of action of new drugs, cellular stress and the role of Unfold Protein Response (UPR) of the endoplasmic reticulum proteins in glioblastoma cell lines.
Glial cells (astrocytes, oligodendrocytes, microglia and ependymocytes), the most numerous in the human brain, provide nutritional support, blood, structural and defense to neurons. They can mutate giving rise to glial tumor cells or glioma, of which 70% are derived from astrocyte cells. The development of tumors is often attributed to an accumulation of genetic changes that allow cells to escape the normal control of proliferation, apoptosis and cell migration. Our group has demonstrated the involvement of heat shock proteins like GRP78 involved in UPR and HSPB1 / HSP27 which have major impact on survival of patients with GBM. Molecular chaperone proteins are considered to be key in maintaining the proteome, since it facilitates the folding of nascent polypeptides, as well as the folding and / or degradation of misfolded proteins. The expression and activity of molecular chaperones are tightly regulated both at transcriptional and posttranslational level in the state of increased oxidative body and consequently the proteotoxic stress, including the state of aging and related diseases such as cancer. To achieve this objective, we plan to investigate: 1) The role of heat shock proteins in cellular stress and UPR on cell glioblastoma cell lines through proliferation assays, cell migration, changes in the proteome based on mass spectrometry and Western blotting validation; 2) Cell intercommunication: Isolation and characterization of proteomic profile of exosomes derived from strains of glioblastoma cell under stress conditions and 3) Mechanisms of action of new drugs sesquiterpene lactone isolated from natural products, AM04 and AM05, compared to temozolomide action. With these proteomic approaches and biological processes is expected to contribute to the achievement of new drugs and increase knowledge of cancer biology.
Sugestões de leitura/Suggestions for further reading
1: Marie SK, Oba-Shinjo SM, da Silva R, Gimenez M, Nunes Reis G, Tassan JP, Rosa JC, Uno M. Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma. Proteome Sci. 2016 Mar 11;14:6. doi:10.1186/s12953-016-0094-9. PubMed PMID: 26973435; PubMed Central PMCID:PMC4788929.
2: Rosa JC, de Cerqueira César M. Role of hexokinase and VDAC in neurological disorders. Curr Mol Pharmacol. 2016 Jan 12. [Epub ahead of print] PubMed PMID:26758954.
3: de Oliveira Souza VC, de Marco KC, Laure HJ, Rosa JC, Barbosa F Jr. A brain proteome profile in rats exposed to methylmercury or thimerosal (ethylmercury). J Toxicol Environ Health A. 2016;79(12):502-12. doi: 10.1080/15287394.2016.1182003. PubMed PMID: 27294299.
4: de Souza AP, Pedroso AP, Watanabe RL, Dornellas AP, Boldarine VT, Laure HJ, do Nascimento CM, Oyama LM, Rosa JC, Ribeiro EB. Gender-specific effects of intrauterine growth restriction on the adipose tissue of adult rats: a proteomic approach. Proteome Sci. 2015 Dec 2;13:32. doi: 10.1186/s12953-015-0088-z. PubMed PMID: 26633942; PubMed Central PMCID: PMC4667418.
5: Lico DT, Lopes GS, Brusco J, Rosa JC, Gould RM, De Giorgis JA, Larson RE. A novel SDS-stable dimer of a heterogeneous nuclear ribonucleoprotein at presynaptic terminals of squid neurons. Neuroscience. 2015 Aug 6;300:381-92. doi: 10.1016/j.neuroscience.2015.05.040. PubMed PMID: 26012490.
6: Gimenez M, Marie SK, Oba-Shinjo S, Uno M, Izumi C, Oliveira JB, Rosa JC. Quantitative proteomic analysis shows differentially expressed HSPB1 in glioblastoma as a discriminating short from long survival factor and NOVA1 as a differentiation factor between low-grade astrocytoma and oligodendroglioma. BMC Cancer. 2015 Jun 25;15:481. doi: 10.1186/s12885-015-1473-9. PubMed PMID: 26108672; PubMed Central PMCID: PMC4502388.
7: Castro-Gamero AM, Izumi C, Rosa JC. Biomarker verification using selected reaction monitoring and shotgun proteomics. Methods Mol Biol. 2014;1156:295-306. doi: 10.1007/978-1-4939-0685-7_20. PubMed PMID: 24791997.
8: Crepaldi CR, Vitale PA, Tesch AC, Laure HJ, Rosa JC, de Cerqueira César M. Application of 2D BN/SDS-PAGE coupled with mass spectrometry for identification of VDAC-associated protein complexes related to mitochondrial binding sites for type I brain hexokinase. Mitochondrion. 2013 Nov;13(6):823-30. doi: 10.1016/j.mito.2013.05.009. PubMed PMID: 23719229.
9: Ramão A, Gimenez M, Laure HJ, Izumi C, Vida RC, Oba-Shinjo S, Marie SK, Rosa JC. Changes in the expression of proteins associated with aerobic glycolysis and cell migration are involved in tumorigenic ability of two glioma cell lines.Proteome Sci. 2012 Sep 3;10(1):53. doi: 10.1186/1477-5956-10-53. PubMed PMID:22943417; PubMed Central PMCID: PMC3547712.
10: Pranchevicius MC, Oliveira LL, Rosa JC, Avanci NC, Quiapim AC, Roque-Barreira MC, Goldman MH. Characterization and optimization of ArtinM lectin expression in Escherichia coli. BMC Biotechnol. 2012 Aug 2;12:44. doi: 10.1186/1472-6750-12-44.PubMed PMID: 22857259; PubMed Central PMCID: PMC3431236.
11: Gimenez M, Marie SK, Oba-Shinjo SM, Uno M, da Silva R, Laure HJ, Izumi C, Otake A, Chammas R, Rosa JC. Quantitative proteomic analysis and functional studies reveal that nucleophosmin is involved in cell death in glioblastoma cell line transfected with siRNA. Proteomics. 2012 Aug;12(17):2632-40. doi:10.1002/pmic.201200034. PubMed PMID: 22745010.
12: Pedroso AP, Watanabe RL, Albuquerque KT, Telles MM, Andrade MC, Perez JD,Sakata MM, Lima ML, Estadella D, Nascimento CM, Oyama LM, Rosa JC, Casarini DE, Ribeiro EB. Proteomic profiling of the rat hypothalamus. Proteome Sci. 2012 Apr 20;10(1):26. doi: 10.1186/1477-5956-10-26. PubMed PMID: 22519962; PubMed Central PMCID: PMC3441799.
13: Spiller F, Costa C, Souto FO, Vinchi F, Mestriner FL, Laure HJ, Alves-Filho JC, Freitas A, Rosa JC, Ferreira SH, Altruda F, Hirsch E, Greene LJ, Tolosano E, Cunha FQ. Inhibition of neutrophil migration by hemopexin leads to increased mortality due to sepsis in mice. Am J Respir Crit Care Med. 2011 Apr 1;183(7):922-31. doi: 10.1164/rccm.201002-0223OC. PubMed PMID: 20971829.
14: Gimenez M, Souza VC, Izumi C, Barbieri MR, Chammas R, Oba-Shinjo SM, Uno M, Marie SK, Rosa JC. Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin. Proteomics. 2010 Aug;10(15):2812-21. doi: 10.1002/pmic.200900722 PubMed PMID: 20533335.
15: Barros BH, da Silva SH, dos ReisMarques Edos R, Rosa JC, Yatsuda AP, Roberts DW, Braga GU. A proteomic approach to identifying proteins differentially expressed in conidia and mycelium of the entomopathogenic fungus Metarhizium acridum. Fungal Biol. 2010 Jul;114(7):572-9. doi: 10.1016/j.funbio.2010.04.007.PubMed PMID: 20943168.
16: Lico DT, Rosa JC, DeGiorgis JA, de Vasconcelos EJ, Casaletti L, Tauhata SB, Baqui MM, Fukuda M, Moreira JE, Larson RE. A novel 65 kDa RNA-binding protein in squid presynaptic terminals. Neuroscience. 2010 Mar 10;166(1):73-83. doi:10.1016/j.neuroscience.2009.12.005. PubMed PMID: 20004709.
17: Tomazella GG, da Silva I, Laure HJ, Rosa JC, Chammas R, Wiker HG, de Souza GA, Greene LJ. Proteomic analysis of total cellular proteins of human neutrophils. Proteome Sci. 2009 Aug 31;7:32. doi: 10.1186/1477-5956-7-32. PubMed PMID: 19719850; PubMed Central PMCID: PMC3224919.
18: Lopes JL, Valadares NF, Moraes DI, Rosa JC, Araújo HS, Beltramini LM.Physico-chemical and antifungal properties of protease inhibitors from Acacia plumosa. Phytochemistry. 2009 May;70(7):871-9. doi: 10.1016/j.phytochem.2009.04.009. PubMed PMID: 19443001.
19: Mestriner FL, Spiller F, Laure HJ, Souto FO, Tavares-Murta BM, Rosa JC, Basile-Filho A, Ferreira SH, Greene LJ, Cunha FQ. Acute-phase protein alpha-1-acid glycoprotein mediates neutrophil migration failure in sepsis by a nitric oxide-dependent mechanism. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19595-600. PubMed PMID: 18048324; PubMed Central PMCID: PMC2148334.
20: Hanneman AJ, Rosa JC, Ashline D, Reinhold VN. Isomer and glycomer complexities of core GlcNAcs in Caenorhabditis elegans. Glycobiology. 2006 Sep;16(9):874-90. PubMed PMID: 16769777.
21: Schachter H, Chen S, Zhang W, Spence AM, Zhu S, Callahan JW, Mahuran DJ, Fan X, Bagshaw RD, She YM, Rosa JC, Reinhold VN. Functional post-translationalproteomics approach to study the role of N-glycans in the development of Caenorhabditis elegans. Biochem Soc Symp. 2002;(69):1-21. Review. PubMed PMID:12655770.
22: Rosa JC, De Oliveira PS, Garratt R, Beltramini L, Resing K, Roque-Barreira MC, Greene LJ. KM+, a mannose-binding lectin from Artocarpus integrifolia: amino acid sequence, predicted tertiary structure, carbohydrate recognition, and analysis of the beta-prism fold. Protein Sci. 1999 Jan;8(1):13-24. PubMed PMID: 10210179;PubMed Central PMCID: PMC2144112.
Complete publications:
URL:http://www.researcherid.com/rid/A-1966-2013
https://scholar.google.com.br/citations?user=OEHuKTwAAAAJ
1)Biomarker discovery in cancer using mass spectrometry-based proteomics.
Our group is interested in the development of functional and structural proteomics of cancer and stem cells. An elaborate gene network is regulated during the control of cell proliferation and differentiation. We focus our research on the products of these genes, the proteins, by studying their differential expression, localization, and interaction with other proteins, since they represent a shortcut between the genome and the development of diseases such as cancer. We also aim to understand the biology of stem cells during self-replenishment and comprehend processes leading to the differentiation of these cells into other cell types. To develop our research, we employ methodologies for the separation of proteins and peptides, namely liquid chromatography, affinity chromatography, and electrophoresis. We identify the protein entities and post-translation alterations (phosphorylation and glycosylation) by mass spectrometry (ESI-MS/MS and MALDI-TOF/TOF). Our major projects involve samples of tumors and clinically relevant cells in glioma (astrocytoma, oligodendroglioma e meduloblastoma), and our main objective is to identify proteins/genes that may serve as disease markers for the diagnosis, prognosis, and potential therapeutic target.
Site: http://cqp.fmrp.usp.br