Axis 1: Hematometabolism in Cardiometabolic Diseases

Heart disease kills more people than any other worldwide. In an effort to understand the underlying mechanisms that cause heart disease, at least two distinct lines of thinking have emerged. First, obesity, diabetes, hypertension, high triglycerides, and low HDL cholesterol – the key constituents of the metabolic syndrome – have been recognized as major risk factors. Second, inflammation – the immune system’s ancient defense program against infection and injury – has surfaced as a critical component accompanying most stages of disease. After a contribution to the development of new therapeutics for cardiovascular diseases at Pfizer, one research axis of our department is now focusing on how metabolic regulation of the hematopoietic tree perturbs chronic inflammatory atherosclerotic cardiovascular disease. More recently, a hypothesis-driven selection of biochemical pathways linking metabolism and inflammation has emerged by filtering ‘Omics’ studies through a topological analysis bioinformatic tools. The metabolic reprogramming of macrophages in atherosclerosis is currently under intense investigation.This work is supported by an European ERC consolidator.

Axis 2: Hematometabolism in Lung cancer

Lung cancer is the most common cancer as well the most frequent cause of cancer death in the world today. Over the last decade, immunotherapy has emerged as a type of revolutionizing treatment that helps the immune system fight cancer. As part of the Oncoage program to foster innovation for cancer management, our goal is to identify the metabolic alterations in cancer that could influence the immune response with the goal of improving immunotherapy response. The plasticity of macrophages has now been largely accepted and is reflected by their ability to sense, respond and rapidly adapt to their local environment, including tumor microenvironment. Tumor cells produce lactate through exacerbated glucose consumption (”Warburg effect”) and compete with surrounding macrophages to limit their cancer-killing potential. We are now evidencing that these dysregulations are only the tip of the iceberg and we are entering an exciting era of precision medicine that should help to better stratify patient populations. These projects are supported by grants from the Fondation ARC, an European Marie Curie Career Integration Grant and a national ATIP-AVENIR starting package.