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Quantitative proteomic analysis in mononuclear (PBMC) and polymorphonuclear (PMN) cell samples from patients with Sepsis and healthy volunteers, focusing on proteins related to energy and oxidative metabolism, as well as mitochondrial function

Grant number: 19/20532-3
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: January 01, 2020
End date: June 30, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Reinaldo Salomão
Grantee:Giuseppe Gianini Figueiredo Leite
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:17/21052-0 - Sepsis: mechanisms, therapeutic targets and epidemiology, AP.TEM
Associated scholarship(s):22/06085-7 - The role of MS1 monocytes in the host response during sepsis and pneumonia, BE.EP.PD

Abstract

The pathogenesis of Sepsis is complex and involves multiple aspects of the interaction between the infecting microorganisms and the host. The recognition of pathogens and the resulting cellular activation are fundamental for infection control. Transcriptomic studies linked to powerful bioinformatics tools have allowed broader assessments of inflammatory, immune, and metabolic phenomena that occur in Sepsis (Calvano et al, 2005, Xiao et al 2011). In our previous project (process 2011/20401-4), conducted from 2012 to 2017, we sought to evaluate the interaction between activation of pathogen and danger signals with oxidative metabolism and oxidative phosphorylation (oxphos) in patients with Sepsis. Our results showed that genes involved in the electron transport chain had their expression altered in septic patients who did not survive (Nucci 2017), confirming previous transcriptomic results (Severino 2014). Similarly, we demonstrated modulation of inflammasome-related genes in Sepsis, with major changes in patients who did not survive (Esquerdo et al, 2017). Additionally, we have shown that up-regulation of heme/hemoglobin metabolism pathways may represent a protective white blood cell response to the hostile environment present in septic patients (Leite et al, 2019). More recently, proteomics has emerged as a powerful tool for identifying biomarkers, functional changes, and mechanisms involved in the pathogenesis of Sepsis (Meissner & Mann, 2014; Sharma & Salomao, 2017). We make efforts in the field of proteomics techniques and their application in Sepsis, with very interesting results obtained in the plasma of septic patients. The results were presented at national and international congresses and published in international journals. Previous plasma proteomics studies have shown that lipid metabolism and acute phase response signaling were among the most altered pathways in septic patients (Cao & Robinson, 2014). Our results pointed to notable changes in cell assembly (cytoskeleton, cell assembly and movement), lipid metabolism, and immune responses in septic patients Sepsis secondary to community-acquired Pneumonia, confirming and broadening previous findings (Sharma et al, 2017). From these results, we intend to perform quantitative proteomic analysis on PBMC and PMN samples from Sepsis patients and healthy volunteers, focusing on proteins related to energy and oxidative metabolism, as well as mitochondrial function and changes that occur after protein translation (PTM, Post Translational Modifications). The postdoctoral fellow will interface between the immunology laboratory (Reinaldo Salomão) and the proteomics unit (Alexandre Keiji Tashima), consolidating the advances made with this technique. Furthermore, he will introduce new tools of systems biology helping to integrate transcriptomics and proteomics results. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
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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)
FERREIRA, BIANCA LIMA; SOUSA, MONICA BRAGANCA; LEITE, GIUSEPPE GIANINI FIGUEIREDO; BRUNIALTI, MILENA KARINA COLO; NISHIDUKA, ERIKA SAYURI; TASHIMA, ALEXANDRE KEIJI; VAN DER POLL, TOM; SALOMAO, REINALDO. Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function. FRONTIERS IN IMMUNOLOGY, v. 13, p. 10-pg., . (16/13855-2, 20/05077-5, 17/21052-0, 19/20532-3)
FIGUEIREDO LEITE, GIUSEPPE GIANINI; FERREIRA, BIANCA LIMA; TASHIMA, ALEXANDRE KEIJI; NISHIDUKA, ERIKA SAYURI; CUNHA-NETO, EDECIO; COLO BRUNIALTI, MILENA KARINA; ASSUNCAO, MURILLO; PONTES AZEVEDO, LUCIANO CESAR; FREITAS, FLAVIO; VAN DER POLL, TOM; et al. Combined Transcriptome and Proteome Leukocyte's Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis. FRONTIERS IN IMMUNOLOGY, v. 12, . (19/20532-3, 17/21052-0, 16/13855-2)