Exploring expansion proteomics to evaluate protein-protein interactions

• Grant number: 25/00104-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 31, 2025
• End date: March 30, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Adriana Franco Paes Leme
• Grantee: Guilherme Araújo Câmara
• Supervisor: Kiryl D Piatkevich
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: Westlake University, China
• Associated to the scholarship: 22/14348-8 - Structural proteomics for the search of therapeutic targets in oral cancer, BP.DR

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer, comprising 90% of all oral malignancies worldwide. The five-year survival rate of patients diagnosed at advanced stages of the disease (Stages III or IV) is approximately 20%, making clear that the discovery of diagnostic and prognostic markers is essential to improve OSCC patients' outcomes, as early detection and treatment are critical for successful management of OSCC. Our group has demonstrated that the spatial downregulation of N-myc downstream-regulated gene 1 (NDRG1), cystatin B (CSTB) and phosphoglycerate kinase 1 (PGK1) in neoplastic islands of the invasive tumor front of OSCC tissue is associated with worse prognostic features. However, the exact role of these proteins on OSCC development remains unclear. Here, we propose the development of a novel strategy based on immunoproximity labeling combined with expansion proteomics for the assessment of CSTB, NDRG1 and PGK1 interactomes with single-cell spatial resolution. For this, we will compare the interactomes of these target proteins on two sites of OSCC formalin-fixed paraffin-embedded (FFPE) tissue, in the invasive tumor front versus inner tumor. We believe that this novel strategy will highlight key protein-protein interactions that are modulated on tissue subregions at different aggressiveness levels. Ultimately, the anticipated results may enable the identification of proteins with potential therapeutic value, enabling the proposal of interventions that may favor a better outcome for OSCC patients.