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Differential expression isoform analysis from oxygen induced retinopathy in a murine model

Grant number: 19/21870-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:João Carlos Setubal
Grantee:Débora Guerra Peixe
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Angiogenesis is the creation of new blood vessels from pre-existing ones. It occurs naturally in physiological and pathological process, such as retinopathies and cancer. Through RNA sequencing (RNA-Seq), it is possible to study these differences between tissues at cell level in the moment of sequencing. RNA-seq data enables the identification and quantification of gene expression of the same tissue in different conditions. Isoforms are found in the majority of eukaryotic genes, through alternative splicing of the same gene and different isoforms may be involved in different processes. VEGF (vascular endothelial growth factor) has a central role in angiogenesis and it's regulation, having a pro or anti angiogenic effect depending on which isoform is expressed. Anti angiogenic drugs usually target VEGF pathways and are often the drug choice for angiogenic-dependent diseases and sometimes, solid tumors. Although antiangiogenic effects are welcome, it's side effects, like hypertension, proteinuria, thrombosis and bleeding, limits it's use . Besides, some patients develops treatment resistance. In solid tumors, antiangiogenic exclusive therapy doesn't increase survival , and in some cases, there is no benefit to the patients. Therefore, it becomes clear that the pathological angiogenesis process is not well known. Studying differentially expressed isoforms in tissues with pathologically formed vessels can bring to light new targets for therapy, increasing specificity and efficacy and reducing side effects.

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