Deciphering molecular pathways in uveal melanoma: uncovering prognostic biomarkers and targeting therapeutic strategies

• Grant number: 25/00962-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Nicolas Jones Villarinho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Uveal melanoma (UM) is the most aggressive form of ocular cancer, poses a formidable challenge due to its high metastatic propensity, a leading cause of patient mortality. Effective therapies for UM metastasis remain elusive. Based on solid preliminary data, in this project I posit that loss of 15-hydroxyprostaglandin dehydrogenase (HPGD), a tumor suppressor gene, promotes UM aggressiveness by affecting tumor cell motility and communication with the microenvironment through extracellular vesicles (tEVs). Using transcriptomics, proteomics, co-culture, tEVs isolation, and classical biological approaches, I will explore how HPGD functions to influence UM motile ability and cell-cell communication, in particular with endothelial cells under shear-stress. This project will provide unprecedented contribution to the melanoma field, as it will dissect the molecular characteristics of HPGD functioning and identify potential vulnerabilities. (AU)