MODELING THE ADRENAL MICROENVIRONMENT IN 3D CULTURES: EFFECTS OF THE WNT PATHWAY ON EXTRACELLULAR MATRIX COMPOSITION AND FUNCTION

• Grant number: 24/14165-6
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Claudimara Ferini Pacicco Lotfi
• Grantee: Jean Lucas Kremer
• Supervisor: David Breault
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 21/04770-1 - Decoding the impact of the microenvironment and signaling pathways on the normal and tumoral adrenal gland, BP.PD

Abstract

This study aims to understand how the Wnt pathway contributes to the formation of the adrenal microenvironment by regulating the extracellular matrix (ECM) using primary 3D culture models of normal rat adrenal gland cells. The adrenal gland, composed of differentiated histological zones, is regulated by various factors, including ECM composition and paracrine signaling. Previous studies indicate that the ECM plays a crucial role in the migration, differentiation, and function of adrenocortical progenitor cells, but the specific mechanisms of this regulation remain unknown. In vivo studies of the normal adrenal gland are limited and practically impossible in humans. Therefore, in vitro alternatives using increasingly complex models may provide a pathway to understanding the mechanisms regulating the adrenal microenvironment under normal conditions and provide a scientific basis for studies in pathological conditions in human cells, such as adrenal tumorigenesis. We are interested in investigating the effects of modulating Wnt pathway factors on ECM composition in primary 3D cultures and studying the direct effects of Wnt ligands on biological processes such as proliferation, differentiation, and cellular function in vitro adrenal microenvironments. Learning to maintain long-term 3D organotypic cultures of adrenal cortex cells in homeostasis will open the possibility for future studies using human adrenal cell cultures.