Professor Manolis Pasparakis

Project description

Atherosclerosis is a progressive disease characterized by the formation of plaques in the sub endothelial space of the large arteries. Atherosclerosis represents the main risk factor for cardiovascular disease and is the leading cause of death in developed countries. Atherosclerosis has been linked to hypercholesterolemia for decades, however in the last years atherosclerosis has been recognized as a chronic inflammatory disease. The development and growth of an atherosclerotic plaque is the result of a chronic non-resolving inflammatory response involving the recruitment and entrapment of monocytes in the subendothelial space, where they mature into macrophages that take up lipids becoming foam cells. The death of lipid-laden macrophages is believed to critically affect the progression of atherosclerosis. In early lesions, apoptotic foam cells are phagocytosed by efferocytes resulting in plaque regression. In advanced lesions inefficient efferocytosis results in the accumulation of dead foam cells that release proinflammatory factors and form a necrotic core within the plaque. The mechanisms regulating macrophage death in atherosclerotic plaques remain poorly understood. The aim of this project is to experimentally address the mechanisms inducing macrophage death in atherosclerotic plaques and their role in the development and progression of atherosclerosis.

  

Manolis Pasparakis’ profile 

Manolis Pasparakis is Professor at the Institute for Genetics at the Faculty of Mathematics and Natural Sciences at the University of Cologne and leads the Mouse Genetics and Inflammation Laboratory. He received his Ph.D. in Biology from the University of Athens and did his postdoctoral training in the group of Professor Klaus Rajewsky in the Department of Immunology at Institute for Genetics in Cologne. He became a group leader at the European Molecular Biology Laboratory (EMBL) Mouse Biology Unit in Monterotondo, where he worked from 2002 to 2005. In 2005, he joined the Institute for Genetics as a professor. He is member of the executive board and coordinator of Research Area E on “Inflammation in Aging-associated Diseases” of the Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated -Diseases (CECAD).

  

Research Interests

The Pasparakis group focuses on studying the role of inflammation in disease pathogenesis. Inflammatory responses are regulated by intracellular signalling cascades such as the NF-κB and MAP kinase pathways that are activated downstream of cytokine receptors (e.g. TNFR, IL-1R) or innate immune receptors (e.g. Toll-like receptors, NOD-like receptors). The NF-κB pathway functions in essentially all mammalian cell types and is activated in response to injury, infection, inflammation and other stressful conditions requiring rapid reprogramming of gene expression. Genes regulated by NF-κB include cytokines and chemokines, adhesion molecules, regulators of cell survival, proliferation and apoptosis, acute phase proteins and proteins important for protection from oxidative stress. Due to its central role in regulating cellular responses to inflammation and injury, the NF-κB pathway is implicated in the pathogenesis of inflammatory diseases and cancer. To study the function of NF-κB and MAP kinase pathways in the pathogenesis of inflammatory diseases in vivo the group focuses on using recombinase-assisted (Cre/loxP) conditional gene targeting in mice, allowing studying gene function in the adult organism in a spatially and temporally controlled manner. Using conditional gene targeting the group studies the role of NF-κB and MAP kinase signalling in mouse models of inflammatory diseases such as atherosclerosis, inflammatory bowel disease, inflammatory skin disease, hepatitis and liver cancer.