Head of Laboratory: Lesley Probert, Ph.D., lesley_probert@hol.gr,
Tel: +30-210-64 78 866/863; Fax: +30-210-64 56 547
 

These studies provided considerable information concerning the role of TNF during the development and function of the immune system, and highlighted its potential to trigger complex inflammatory disease phenotypes resembling rheumatoid arthritis, multiple sclerosis, cachexia, and inflammatory bowel disease in mice when chronically expressed. These transgenic systems represent experimental models for human disease and are widely used in both academic and bioindustrial communities for in vivo verification of disease mechanisms and testing of anti-TNF drugs prior to their use for the treatment of human disease. While these studies identified important therapeutic reagents that are now used for treatment of arthritis and IBD in patients, curiously, clinical trials using TNF blocking agents in MS patients reported adverse effects, and spontaneous development of MS has been reported in patients with rheumatoid arthritis and Crohn’s disease treated with anti-TNF medication. These latter findings strongly suggested that further to its deleterious pro-inflammatory effects, TNF also exerts significant beneficial effects specifically in the CNS.

Our current research is focused on:
 

A) understanding the cellular and molecular mechanisms that underlie the beneficial roles of TNF and CNS inflammation, and their importance as a host/tissue defense response of the brain to injury and infection. Particular focus is placed on studying:

1) How extrinsically-triggered apoptotic pathways can control both neuron death and neuron survival following ishemic and excitotoxic injury, and how these pathways can be manipulated using cell-penetrating peptides/small protein analogues of key mediators with a view to developing novel neuroprotective agents 2) How bi-directional communication is established between the inflamed brain and the immune system, and how this cross-talk can shape protective autoimmunity  3) How the brain inflammatory process makes the commitment to convert its antibacterial, tissue-damaging (but neuroprotective) response to injury into promotion of endogenous repair mechanisms and restoration of tissue homeostasis

1. T cell differentiation and
2. Memory formation, with the aim of understanding how environmental cues from inflammatory tissues or sites of immune privilege can influence the development and outcome of adaptive immune responses. Delineation of these mechanisms is fundamental to our understanding of how the CNS defends itself during immune attack, injury and infection, and of how this response can succeed to maintain tissue homeostasis, or fail resulting in neuropat hology, and how it can be manipulated to achieve novel therapeutic approaches

The Laboratory is fully equipped to cover most methodologies in molecular and cellular biology, immunology and neurobiology and a special emphasis is given to the development of technology and transfer of expertise in the following areas;