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Systemic and integrative analysis of molecular mechanisms associated with immunoregulation in patients with COVID-19

Grant number: 20/09146-1
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): August 01, 2020
Effective date (End): October 31, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Otávio Cabral Marques
Grantee:Paula Paccielli Freire-Barguil
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19, AP.R


The current pandemic of the Coronavirus respiratory disease 2019 (COVID-19) represents a state of international public emergency. The virus causing the disease is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has been circulating throughout the world, triggering clinical manifestations ranging from asymptomatic cases to severe acute respiratory syndrome and death, especially of individuals with comorbidities (ex: hypertension, asthma, and diabetes). Thus, suggesting the influence of immunological and other host factors in controlling the development of the disease. Meanwhile, patients who develop severe illness may die due to intense immune dysregulation and a high release of cytokines. The knowledge about the systemic immunological mechanisms that control the protection against SARS-CoV-2 is still scarce and the systemic aspects of molecular mechanisms controlling immunoregulation remain to be characterized. The hypothesis of this project is that genes associated with the immunoregulation of patients with COVID-19 have a specific systemic molecular profile, influencing the severity of the disease phenotype. Thus, this project aims characterize the molecular mechanisms associated with immunoregulation in patients infected with SARS-CoV-2, with mild and severe COVID-19. We will carry out a systemic and integrative approach, investigating the transcriptome of immune cells, followed by specific functional assays to validate the high-throughput screening (transcriptome analysis). In addition, we will perform a meta-analysis of data previously uploaded to ArrayExpress and GEO (Gene Expression Omnibus) to determine the networks of gene co-expression that systemically regulate the immune response to SARS-CoV-2. This high-throughput approach analysis will allow us to define the immunological signatures, signaling pathways and networks of gene co-expression and the molecular (interactome) and metabolic (metabolome) interactions involved in the immune response against SARS-CoV-2. Then, will promote a translational and multidisciplinary study that can identify biomarkers for the differential diagnosis. This fact will pave the way for the development of new specific therapies that reduce mortality and morbidity induced by the virus. (AU)

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Scientific publications (9)
(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)
GONCALVES, RENATA DE CASTRO; FREIRE, PAULA PACCIELLI; COLETTI, DARIO; SEELAENDER, MARILIA. Tumor Microenvironment Autophagic Processes and Cachexia: The Missing Link?. FRONTIERS IN ONCOLOGY, v. 10, . (20/09146-1, 12/50079-0, 20/07765-6)
PRADO, CAROLINE ALIANE DE SOUZA; FONSECA, DENNYSON LEANDRO M.; SINGH, YOUVIKA; FILGUEIRAS, IGOR SALERNO; BAIOCCHI, GABRIELA CRISPIM; PLACA, DESIREE RODRIGUES; MARQUES, ALEXANDRE H. C.; DANTAS-KOMATSU, RAQUEL COSTA SILVA; USUDA, JULIA N.; FREIRE, PAULA PACCIELLI; et al. Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity. Journal of Medical Virology, v. 95, n. 2, p. 18-pg., . (20/11710-2, 20/09146-1, 20/16246-2, 20/01688-0, 20/07069-0, 20/07972-1, 18/18886-9)
FONSECA, DENNYSON LEANDRO M.; FILGUEIRAS, IGOR SALERNO; MARQUES, ALEXANDRE H. C.; VOJDANI, ELROY; HALPERT, GILAD; OSTRINSKI, YURI; BAIOCCHI, GABRIELA CRISPIM; PLACA, DESIREE RODRIGUES; FREIRE, PAULA P.; POUR, SHAHAB ZAKI; et al. Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach. NPJ AGING, v. 9, n. 1, p. 14-pg., . (20/11710-2, 20/09146-1, 20/16246-2, 20/01688-0, 20/07069-0, 20/07972-1, 18/18886-9)
BORGES, LYSANDRO P.; GUIMARAES, ADRIANA G.; FONSECA, DENNYSON LEANDRO M.; FREIRE, PAULA P.; BARRETO, IKARO D. C.; SOUZA, DANIELA R., V; GURGEL, RICARDO Q.; LOPES, ALINE S. A.; DE REZENDE NETO, JOSE MELQUIADES; DOS SANTOS, KEZIA A.; et al. Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities. HELIYON, v. 8, n. 11, p. 11-pg., . (20/01688-0, 18/18886-9, 20/09146-1, 20/07069-0)
FREIRE, PAULA P.; MARQUES, ALEXANDRE H. C.; BAIOCCHI, GABRIELA C.; SCHIMKE, LENA F.; FONSECA, DENNYSON L. M.; SALGADO, RANIERI C.; FILGUEIRAS, IGOR S.; NAPOLEAO, SARAH M. S.; PLACA, DESIREE R.; AKASHI, KAREN T.; et al. The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2-infected patients by sex and age. JCI INSIGHT, v. 6, n. 10, . (20/09146-1, 20/01688-0, 17/05264-7, 13/50343-1, 20/07069-0, 20/07972-1)
CABRAL-MARQUES, OTAVIO; HALPERT, GILAD; SCHIMKE, LENA F.; OSTRINSKI, YURI; VOJDANI, ARISTO; BAIOCCHI, GABRIELA CRISPIM; FREIRE, PAULA PACCIELLI; FILGUEIRAS, IGOR SALERNO; ZYSKIND, ISRAEL; LATTIN, MIRIAM T.; et al. Autoantibodies targeting GPCRs and RAS-related molecules associate with COVID-19 severity. NATURE COMMUNICATIONS, v. 13, n. 1, p. 12-pg., . (20/07069-0, 18/18886-9, 20/16246-2, 20/11710-2, 20/07972-1, 20/09146-1, 20/01688-0)
CURY, S. S.; OLIVEIRA, J. S.; BIAGI-JUNIOR, C. A. O.; SILVA JR, W. A.; REIS, P. P.; CABRAL-MARQUES, O.; HASIMOTO, E. N.; FREIRE, P. P.; CARVALHO, R. F.. Transcriptional profiles and common genes link lung cancer with the development and severity of COVID-19. Gene, v. 852, p. 11-pg., . (13/50343-1, 20/09146-1)
FILGUEIRAS, IGOR SALERNO; TORRENTES DE CARVALHO, AMANDA; CUNHA, DANIELA PRADO; MATHIAS DA FONSECA, DENNYSON LEANDRO; EL KHAWANKY, NADIA; FREIRE, PAULA PACCIELLI; CABRAL-MIRANDA, GUSTAVO; SCHIMKE, LENA F.; CAMARA, NIELS OLSEN SARAIVA; OCHS, HANS D.; et al. The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. PLoS Neglected Tropical Diseases, v. 15, n. 8, . (18/18886-9, 20/09146-1, 17/05264-7, 20/01688-0)
DANTAS-KOMATSU, RAQUEL COSTA SILVA; CRUZ, MARINA SAMPAIO; FREIRE, PAULA PACCIELLI; DINIZ, ROSIANE VIANA ZUZA; BORTOLIN, RAUL HERNANDES; CABRAL-MARQUES, OTAVIO; SOUZA, KAMILLA BATISTA DA SILVA; HIRATA, MARIO HIROYUKI; HIRATA, ROSARIO DOMINGUEZ CRESPO; REIS, BRUNA ZAVARIZE; et al. The let-7b-5p, miR-326, and miR-125a-3p are associated with left ventricular systolic dysfunction in post-myocardial infarction. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 10, p. 11-pg., . (20/09146-1, 18/18886-9, 20/01688-0, 20/07069-0)

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