Scientific cooperation for the investigation of the role of endoproteases and their substrates in lipid metabolic regulation and their implications for obesity and hepatic steatosis

• Grant number: 24/19283-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Carlos Arterio Sorgi
• Grantee: Carlos Arterio Sorgi
• Principal researcher abroad: Antoine Dufour
• Institution abroad: University of Calgary, Canada
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 24/03414-5 - Integrated Analysis of Sphingolipid Metabolism and Extracellular Particle Composition in the Context of a Hight-Fat-Diet: Implications for Lipoproteins, Vesicle Biogenesis, and the Role in Macrophage Response to COVID-19, AP.R

Abstract

Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix remodeling and inflammation through proteolytic processing of cytokines and chemokines. Diversal MMPs are expressed by macrophages and contribute to development and progression of many diseases including cancer, autoimmune diseases, and atherosclerotic cardiovascular disease. Indeed, it is suggested that some novel identified substrates of MMPs are fundamental regulators of lipid homeostasis. This project aims to establish a collaborative research initiative between the University of São Paulo (USP) and the University of Calgary, focusing on the interplay between lipid metabolism and protease activity in the context of obesity and inflammation. The proposed research will leverage the expertise of Prof. Carlos Sorgi, a leader in lipid biochemistry and inflammation markers, and Prof. Antoine Dufour, an expert in proteomics and systems biology. Through a series of exchange activities, including workshops and seminars, the teams will develop a joint research framework centered on how lipids modulate macrophage immune responses and how proteolytic modifications influence these processes. We will integrate experimental data from murine models, cell culture studies, and clinical samples, utilizing advanced techniques such as quantitative and tandem-mass spectrometry to profile lipid and protease dynamics. The collaboration aims to identify biomarkers and regulatory pathways associated with metabolic dysfunction and immune dysregulation, ultimately targeting therapeutic interventions for obesity-related complications. By establishing robust training programs and facilitating student exchanges, the project will build capacity within both institutions while fostering interdisciplinary collaboration. The resulting collaborative project will ensure sustained partnership and continued exploration of lipids and protease roles in disease mechanisms, with potential implications for public health strategies against infectious diseases and metabolic disorders. (AU)