Targeting the MyD88 signaling network for the treatment of inflammatory and autoimmune diseases
Speaker: Sir Philip Cohen, Ph.D. MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences. University of Dundee. Scotland (UK)
Organizers: IRB Barcelona
Date: Friday 30 September 12:00h
Place: Felix Serratosa, Parc Científic de Barcelona, Spain
Host: Ángel R.Nebreda, PhD, IRB Barcelona
The MyD88 signaling network controls the production of many inflammatory mediators and is critical for protection against infection by microbial pathogens. However, the hyper-activation of the pathway and/or failure to terminate inflammation once it has done its job causes a variety of inflammatory and autoimmune diseases and even lymphoma. In the seminar, I will discuss several aspects of the on-going research in my lab that are relevant to these topics. First, the discovery that activation of the MyD88 signaling network rapidly triggers the formation of hybrid ubiquitin chains containing both Lys63 and Met1 linkages that facilitate both activation and suppression of the system. Second, the identification of mechanisms that restrict the activation of the MyD88 signaling network to prevent lupus. Third the discovery of a protein kinase subfamily that restrict the conversion of inflammatory macrophages to the anti-inflammatory macrophages thought to be critical for the resolution of inflammation. Finally, I will present unexpected findings, which have revealed that the “textbook” accounts of how the MyD88-dependent signaling network operates require significant revision.