Combining omics strategies can indicate potential targets involved in the Oral Cancer initiation through extracellular vesicle communication

• Grant number: 20/11709-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2020
• Effective date (End): September 30, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal researcher: Adriana Franco Paes Leme
• Grantee: João Vitor Silva Ormonde
• Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
• Associated research grant: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation, AP.TEM

Abstract

This project has the objective to combine omics strategies to answer our reductionist hypotheses that (1) alcohol alters resting fibroblast and/or keratinocyte-derived EVs; (2) alcohol-altered EVs can modify the cell microenvironment phenotype; (3) the selected EV proteins are candidates as therapeutic targets. The Post-Doctorate (PD) will be responsible in the first hypothesis to evaluate miRNA, protein, metabolite and lipid composition of alcohol-treated and non-treated fibroblast and keratinocyte-derived EVs. In the second hypothesis, the PD will perform laser microdissection followed by single-cell RNAseq and mass spectrometry-based discovery proteomics of primary site and lymph node tissues of an orthotopic mouse model injected with alcohol-treated and non-treated fibroblast and keratinocyte-derived EVs. The protein expression of potential candidates indicated using in vitro and animal studies will be evaluated in known altered phenotype, the human samples, using EVs from biopsy and EVs from plasma of oral potentially malignant lesions (Leukoplakia) and early stage Oral Squamous Cell Carcinoma (T1/2N0 and T1/2N+) using targeted mass spectrometry approaches. Finally, in the third hypothesis, the selected candidates will be tested as therapeutic targets. In summary, this project will integrate the in vitro, animal and human data to provide the potential candidates as therapeutic targets involved in the initiation of Oral Cancer. (AU)