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Decoding the impact of microenvironment and signaling pathways in health and disease in brain, adrenal gland and kidney

Grant number: 20/02988-7
Support Opportunities:Research Projects - Thematic Grants
Duration: April 01, 2021 - March 31, 2026
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Suely Kazue Nagahashi Marie
Grantee:Suely Kazue Nagahashi Marie
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Claudimara Ferini Pacicco Lotfi ; Luiz Fernando Onuchic ; Sueli Mieko Oba Shinjo
Associated researchers: Antonio Marcondes Lerario ; Bartholomeus Johannes Leonardus Eggen ; Giuseppe Palmisano ; Mara Sanches Guaragna ; Maria Candida Barisson Villares Fragoso ; Marina Trombetta Lima ; Matthew Gordon Sampson ; Mauricio da Silva Baptista ; Roseli da Silva Soares
Associated grant(s):21/03412-4 - Multi-user equipment approved in grant 20/02988-7: 10x Genomcis library prep system, AP.EMU
Associated scholarship(s):23/17456-9 - Differentially expressed genes in different brain regions with a focus on the matrisome, BP.IC
23/06272-4 - Study of the correlation between the mutational status of CTNNB1 and BRAF with the radiological presentation of Adamantinomatous Craniopharyngiomas, BP.IC
23/06521-4 - Predictive circulating biomarkers for cognitive impairment in individuals with type 2 diabetes mellitus, BP.PD
+ associated scholarships 22/11567-0 - Proteomic analysis of extracellular and transcriptomic matrix in glomerular development and Idiopathic Collapsing Glomerulopathy, BP.PD
21/05785-2 - Study of the effects of the extracellular matrix on the cellular components of the normal and tumoral adrenal gland, BP.IC
21/03974-2 - Study of the extracellular matrix of the adrenal glands, BP.IC
21/02771-0 - Proteoglycans: distribution of gene and protein expressions in brain sites and age-related variations, BP.IC
21/04770-1 - Decoding the impact of the microenvironment and signaling pathways on the normal and tumoral adrenal gland, BP.PD - associated scholarships


The Extracellular Matrix (ECM) differs greatly across organs owing to complex variations required for specific organ structure and function. ECM modulates cell behavior and regulates cell-cell interactions in physiological mechanisms, processes largely dependent on modulation of cell signaling pathways. Disruptions of these mechanisms may lead to disease. In the current project we propose to decode ECM composition, its interactions with different cellular components, and signaling pathways in homeostatic and pathological conditions of three organs that share individual cells with biological resemblance, namely brain, adrenal gland, and kidney. Our aims include: 1) to decode the ECM composition in health and disease by proteomic analysis; 2) to study the crosstalk between the ECM and the cellular components, concerning signaling pathways, by single-cell transcriptomic approach; 3) to address the impact of the ECM changes in experimental 2D, 3D and animal models; and 4) to identify novel therapeutic possibilities targeting ECM components and altered signaling pathways, by building a 3D organotypic model in a microfluidic platform for drug screening and generating strategic, novel omics data. We expect to identify (dis)similarities between human and experimental animal ECM composition to refine the validity of laboratory animal models to address human diseases. We also expect to determine key ECM components that impact on cellular phenotype and signaling pathways in health and disease. The use of 3D organotypic models including the unraveled ECM characteristics is expected to closely mimic human organs and reduce the number of animal experiments in pre-clinical trials. (AU)

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Scientific publications (8)
(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)
V.A. FEITOSA; P.D.M.M. NEVES; L.B. JORGE; I.L. NORONHA; L.F. ONUCHIC. Renal amyloidosis: a new time for a complete diagnosis. Brazilian Journal of Medical and Biological Research, v. 55, . (20/02988-7)
DAMIANO, RODOLFO FURLAN; ROCCA, CRISTIANA CASTANHO DE ALMEIDA; SERAFIM, ANTONIO DE PADUA M.; LOFTIS, JENNIFER; TALIB, LEDA LEME; PAN, PEDRO MARIO; CUNHA-NETO, EDECIO; KALIL, JORGE; DE CASTRO, GABRIELA SALIM; SEELAENDER, MARILIA F.; et al. Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers. FRONTIERS IN IMMUNOLOGY, v. 14, p. 13-pg., . (22/01769-5, 21/14379-8, 20/02988-7)
MOREIRA FRANCO, YOLLANDA E.; ALVES, MARIA JOSE; UNO, MIYUKI; MORETTI, ISABELE FATTORI; TROMBETTA-LIMA, MARINA; DE SIQUEIRA SANTOS, SUZANA; DOS SANTOS, ANCELY FERREIRA; ARINI, GABRIEL SANTOS; BAPTISTA, MAURICIO S.; LERARIO, ANTONIO MARCONDES; et al. Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness. CANCER & METABOLISM, v. 9, n. 1, . (13/02162-8, 20/02988-7, 15/26328-8, 13/07937-8, 04/12133-6)
PEREIRA, BENEDITO JAMILSON ARAUJO; LERARIO, ANTONIO MARCONDES; SOLA, PAULA RODRIGUES; LAURENTINO, TALITA DE SOUSA; MOHAN, DIPIKA R.; ALMEIDA, ANTONIO NOGUEIRA DE; DE AGUIAR, PAULO HENRIQUE PIRES; PAIVA, WELLINGSON DA SILVA; WAKAMATSU, ALDA; TEIXEIRA, MANOEL JACOBSEN; et al. Impact of a cell cycle and an extracellular matrix remodeling transcriptional signature on tumor progression and correlation with EZH2 expression in meningioma. JOURNAL OF NEUROSURGERY, v. 138, n. 3, p. 14-pg., . (20/02988-7, 13/02162-8, 04/12133-6)
FEITOSA, V. A.; NEVES, P. D. M. M.; JORGE, L. B.; NORONHA, I. L.; ONUCHIC, L. F.. Renal amyloidosis: a new time for a complete diagnosis. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, p. 15-pg., . (20/02988-7)
MACEDO-DA-SILVA, JANAINA; ROSA-FERNANDES, LIVIA; GOMES, VINICIUS DE MORAIS; SANTIAGO, VERONICA FEIJOLI; SANTOS, DEIVID MARTINS; MOLNAR, CATARINA MARIA STANISCHESK; BARBOZA, BRUNO RAFAEL; DE SOUZA, EDMARCIA ELISA; MARQUES, RODOLFO FERREIRA; BOSCARDIN, SILVIA BEATRIZ; et al. Protein Arginylation Is Regulated during SARS-CoV-2 Infection. Viruses-Basel, v. 15, n. 2, p. 25-pg., . (18/15549-1, 18/18257-1, 20/06409-1, 22/09915-0, 20/02988-7, 21/00140-3, 20/12277-0, 21/14179-9, 15/26722-8)
MORETTI, ISABELE FATTORI; LERARIO, ANTONIO MARCONDES; SOLA, PAULA RODRIGUES; MACEDO-DA-SILVA, JANAINA; BAPTISTA, MAURICIO DA SILVA; PALMISANO, GIUSEPPE; OBA-SHINJO, SUELI MIEKO; MARIE, SUELY KAZUE NAGAHASHI. GBM Cells Exhibit Susceptibility to Metformin Treatment According to TLR4 Pathway Activation and Metabolic and Antioxidant Status. CANCERS, v. 15, n. 3, p. 18-pg., . (20/04923-0, 18/18257-1, 04/12133-6, 20/02988-7, 21/00140-3, 13/07937-8)
SEKIYA, FELIPE SEITI; DA SILVA, CLARISSE PEREIRA NUNES; OBA-SHINJO, SUELI MIEKO; SANTOS-BEZERRA, DANIELE PEREIRA; RAVAGNANI, FELIPE GUSTAVO; PASQUALUCCI, CARLOS AUGUSTO; GIL, SAULO; GUALANO, BRUNO; BAPTISTA, MAURICIO DA SILVA; CORREA-GIANNELLA, MARIA LUCIA; et al. Identification of two patterns of mitochondrial DNA-copy number variation in postcentral gyrus during aging, influenced by body mass index and type 2 diabetes. Experimental Gerontology, v. 168, p. 8-pg., . (17/13552-2, 20/02988-7, 20/08091-9, 13/07937-8, 16/15603-0)

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