Identification of a new ligand for Tie1, an orphan receptor important in angiogenesis

• Grant number: 14/15489-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 01, 2014
• End date: March 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ricardo Jose Giordano
• Grantee: Leila da Silva Magalhães
• Supervisor: Renata Pasqualini
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of New Mexico (UNM), United States
• Associated to the scholarship: 10/17610-8 - Identification of ligands for tyrosine kinase receptor Tie-1, BP.DD

Abstract

Angiogenesis is the process of blood vessels formation from preexisting vessels. Angiogenesis is important for physiological and pathological processes, such as cancer and retinopathy. Current anti-angiogenic therapies affect the homeostasis of normal blood vessels. Therefore, it is important to better understand the molecular mechanisms of angiogenesis as such knowledge might help the development of better and more selective therapeutic alternatives for disease with an angiogenesis component. In this sense, our studies are directed to the orphan receptor tyrosine kinase Tie-1. This receptor is expressed by endothelial cells as its role in angiogenesis is still unclear. We are particularly interested in identifying a ligand for this receptor. Thus, we selected and validated by Phage Display a Tie-1 binding peptide (called PLT-1) which has anti-angiogenic effect. Based on protein data base searches using our Tie1 binding peptide, Mucin-4 has been identified as a potential ligand for this receptor. In this project, we propose to perform experiments in the Cancer Center of the University of New Mexico, United States, to further validate this finding as a novel ligand for Tie-1. (AU)