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Functional analysis of LXN gene in vitro and in vivo and genes global expression evaluation in primary erythroid culture after HbF induction through the compound decitabine

Grant number: 17/21892-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2017
Effective date (End): November 30, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fernando Ferreira Costa
Grantee:Renata Sesti Costa
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

LXN gene that encodes a latexina carboxipeptidases-inhibited showed increased expression in the intermediate and final stages of erythroid differentiation in previous results published by our group. The gene silencing in K562 was able to reduce the expression of alpha and gamma globins genes and HbF production after eritropoese induction. In vivo model, zebrafish embryos silenced for LXN showed anemic phenotype in 72hpf. Additionally, the global genes expression study previously identified by numerous functions can also provide important information in the production of hemoglobin. The identification of differentially expressed genes in the production of HbF in cell culture can contribute to a better understanding of the mechanisms involved in their synthesis. Thus, two distinct studies are proposed in this project. First, to give continuity to the functional evaluation of LXN gene, in vitro, using primary culture of CD34 cells and, in vivo, using the zebrafish animal model. And as the second goal, assess globally, the expression of transcription factors and proteins involved in epigenetic changes in cell culture CD34, after inducing production of HbF via composed decitabine.