Identification of ligands for tyrosine kinase receptor Tie-1

• Grant number: 10/17610-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2010
• End date: December 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ricardo Jose Giordano
• Grantee: Leila da Silva Magalhães
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 14/15489-8 - Identification of a new ligand for Tie1, an orphan receptor important in angiogenesis, BE.EP.DD

Abstract

Angiogenesis is the process of blood vessels formation form pre-existing ones. It is important in phyisiological processes such as female menstrual cycle and wound healing, but it is also required for diseases such as cancer and retinopathy. Current anti-angiogenic therapies show promising results but also affect the homeostasis of normal blood vessels resulting in unwanted side effects. Therefore, it is important tobetter understandthe molecular mechanisms of angiogenesis.In our laboratory, we want assessthe role of extracellular domains of tyrosine kinase receptorsin angiogenesis and thus contribute to the development of more selective therapeutic alternatives. Our studies are focused on the orphan tyrosine kinase receptor Tie-1. This receptor is expressed by endothelial cells and its role in angiogenesis is still unclear. The aim of this study to identify a new ligand for Tie-1 and its possible roles of in angiogenesis. In order to achieve our goals, we selected by phage display a Tie-1 Ligand Peptide (called PLT) and validates its binding and specificity in vitro. We show that this peptide has an anti-angiogenic effect in vivo using the model of oxygen-induced retinopathy. Now, we want to validate at the protein level the interaction between Tie-1 and its new identified ligand. If successful, our results contribute to the field and to the development of novel alternatives for angiogenic therapies. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MAGALHÃES, Leila da Silva. The importance of Tyrosine Kinase Receptor Tie1 extracellular domain in angiogenesis. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.