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Human thymus: development and diseases

Grant number: 14/50489-9
Support type:Research Projects - Thematic Grants
Duration: November 01, 2015 - October 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Magda Maria Sales Carneiro-Sampaio
Grantee:Magda Maria Sales Carneiro-Sampaio
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Carlos Alberto Moreira Filho ; Chong Ae Kim ; Cristina Miuki Abe Jacob ; Leslie Domenici Kulikowski
Associated grant(s):15/26778-3 - Multi-user equipment approved in grant 2014/50489-9:Elastography ultrasound for safe research dimensions and organ texture in children - elastography, AP.EMU
Associated scholarship(s):17/08981-1 - Investigation of the cytogenomic profile in 22q11.2 deletion carriers: CNVs x gene expression and immunophenotypic variability, BP.PD
16/18280-8 - Human thymus functional genomics: detection of communities in gene coexpression networks and study of transcriptional control, BP.PD

Abstract

The thymus continues to be a neglected organ, both in research and in clinical practice. Compared to bone marrow, in which intrinsic diseases and deleterious effects of drugs have been well explored, thymus has not received equivalent attention. This project continues a previous one named “Early-onset autoimmunity” (FAPESP grant 2008/58234-4), in which one of the subprojects dealt with functional study of thymus, and allowed assessment of the organ function in patients with Down syndrome and DiGeorge syndrome (22q11.2 deletion), two human chromosomopathies with thymic dysfunction. Considering: i) the numerous series of well-characterized patients followed-up at the Instituto da Criança, ii) access to a large number of thymus specimens, iii) availability of methods for morphological and functional study of the organ [measurement of TRECs (thymic recent emigrant cells) imaging techniques in clinical practice, microscopy, flow cytometry, gene expression platform, bioinformatics], in this new project, we intend to perform: 1) Morphological and functional assessment of thymus in healthy infants and children of various ages; 2) Study of global gene expression in the thymus, as well as network of interactions between genes in infants and children of various ages and in infants and children with Down syndrome (DS); 3) Characterization of B lymphocyte subpopulations in thymus of children of various ages with congenital heart disease as an isolated malformation, and in DS children; 4) Evaluation of phenotype-genotypic relationship and characterization of immune alterations in patients with typical and atypical 22q11.2 deletion; 5) Evaluation of morphological and functional thymic changes in children with primary immunodeficiencies and systemic autimmune diseases undergoing immunosuppressive therapy. It is expected to bring contributions to better knowledge of human thymus development as well as for pathophysiology of some primary and secondary thymic diseases, that may open possibilities for optimal management of affected patients. A new program of thymus transplant should be implemented at Instituto da Criança. It is also expected to simulate the interest of the physicians in the clinical exploration of the thymus. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Study characterize genomic dysregulation in thymus of infants with Down syndrome 

Scientific publications (4)
(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)
LEVY, A.; RANGEL-SANTOS, A.; TORRES, L. C.; SILVEIRA-ABREU, G.; AGENA, F.; CARNEIRO-SAMPAIO, M. T cell receptor excision circles as a tool for evaluating thymic function in young children. Brazilian Journal of Medical and Biological Research, v. 52, n. 7 2019. Web of Science Citations: 0.
MOREIRA-FILHO, CARLOS ALBERTO; BANDO, SILVIA YUMI; BERTONHA, FERNANDA BERNARDI; FERREIRA, LEANDRO RODRIGUES; VINHAS, CHRISTIANA DE FREITAS; BOURGUIGNON OLIVEIRA, LUCILA HABIB; NOGUEIRA ZERBINI, MARIA CLAUDIA; FURLANETTO, GLAUCIO; CHACCUR, PAULO; CARNEIRO-SAMPAIO, MAGDA. Minipuberty and Sexual Dimorphism in the Infant Human Thymus. SCIENTIFIC REPORTS, v. 8, SEP 3 2018. Web of Science Citations: 2.
NOVAK, E. M.; HALLEY, N. S.; GIMENEZ, T. M.; RANGEL-SANTOS, A.; AZAMBUJA, A. M. P.; BRUMATTI, M.; PEREIRA, P. L.; VINCE, C. S. C.; GIORGI, R. R.; BENDITE, I.; CRISTOFANI, L. M.; ODONE-FILHO, V. BLM germline and somatic PKMYT1 and AHCY mutations: Genetic variations beyond MYCN and prognosis in neuroblastoma. Medical Hypotheses, v. 97, p. 22-25, DEC 2016. Web of Science Citations: 1.
MOREIRA-FILHO, CARLOS ALBERTO; BANDO, SILVIA YUMI; BERTONHA, FERNANDA BERNARDI; SILVA, FILIPI NASCIMENTO; COSTA, LUCIANO DA FONTOURA; FERREIRA, LEANDRO RODRIGUES; FURLANETTO, GLAUCIO; CHACUR, PAULO; NOGUEIRA ZERBINI, MARIA CLAUDIA; CARNEIRO-SAMPAIO, MAGDA. Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants. ONCOTARGET, v. 7, n. 7, p. 7497-7533, FEB 16 2016. Web of Science Citations: 2.

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