Dr Ruaidhri Carmody
Since its discovery some 20 years ago, the NF-κB family of proteins has become one of the most important transcription factors relevant to human health and disease. This is due in large part to its pleiotropic effects, its tightly regulated inducibility and its central role in the control of immunity and inflammation. While intense study of the receptor associated events leading to NF-κB activation has resulted in the identification of a complex cytoplasmic regulatory network, comparatively little is known about the regulation of NF-κB nucleus. My research interests lie in identifying key nuclear events that shape the transcriptional outcome of receptor activated NF-κB. We identified the nuclear IκB protein Bcl-3 as a key regulator of NF-κB transcriptional activity during Toll-like receptor signalling. The interaction of Bcl-3 with NF-κB p50 homodimers prevents their ubiquitination and proteasomal degradation, leading to the formation of a stable repressor complex. This Bcl-3:p50 homodimer complex competes with transcriptionaly competent NF-κB dimers for a finite number of DNA binding sites, thereby negatively regulating gene transcription. This Bcl-3:p50 homodimer complex is also of critical importance in promoting a non-responsive state in macrophage following chronic or repeated stimulation through Toll-like receptors, termed tolerance, which is essential for limiting inflammation-induced injury to host tissue. We are very interested in identifying and understanding additional regulators of Toll-like receptor tolerance at the transcriptional level.
More recently, we have identified the first de-ubiquitinase enzyme for NF-κB, Ubiquitin Specific Protease 7, and revealed that the balance of ubiquitination and de-ubiquitination of the NF-κB subunit p65 in the nucleus is fundamental to the control of target gene transcription.
We continue to identify nuclear regulatory events which shape the activity of NF-κB. In addition to revealing fundamental aspects of the control of transcription during inflammation our work also identifies novel therapeutic targets relevant to the treatment of inflammatory disease.
Dr Carl Goodyear
Director, GLAZgo Discovery Centre
Senior Lecturer, Institute of Infection, Immunity and Inflammation
University of Glasgow
Dr Carl Goodyear studied at the University of Glasgow and Glasgow Caledonian University, gaining a BSc with honours in Molecular Biology in 1996 and a PhD in Molecular Immunology in 1999. Upon completing his PhD, Dr Goodyear moved to the US and worked in the Department of Medicine at the University of California at San Diego where he held the position of Assistant Professor. During this period Dr Goodyear was awarded a Cancer Research Institute Postdoctoral Fellowship, became a National Blood Foundation Scholar, and received a number of awards including the National Blood Foundation David B. Pall Prize for Innovative Research in Transfusion Medicine and an Arthritis Foundation Investigator Award. In 2006 he returned to work in the UK at the Institute of Infection Immunity and Inflammation in the University of Glasgow. He was awarded a prestigious Arthritis Research UK Fellowship and shortly after became a Senior Lecturer. Dr Goodyear’s research has continued to gain awards such as the Inaugural Medical Research Scotland Vipiana Award.
Dr Goodyear’s research group is currently focused on understanding immunopathogenesis of disease (i.e., Rheumatoid Arthritis, Osteoarthritis & Multiple Myeloma) and translating this knowledge into viable therapeutic agents for patients. In parallel, Dr. Goodyear also leads a Translational Immunology programme, which provides the critical interface between clinical and basic science.
Dr Matthew Catley
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