Steve Ley is Professor of Molecular Immunology in the Department of Immunology & Inflammation, based at the Hammersmith Campus.
Professor Ley trained in Cellular Immunology for his PhD at the University of Cambridge, UK. He became interested in the molecular analysis of immune responses during his postdoctoral training (1986-1992) at the Dana-Farber Cancer Institute (Harvard University, Boston, USA) and Imperial Cancer Research Fund (London, UK). He continued his Molecular Immunology research as an independent investigator at the MRC National Institute for Medical Research (1992-2015), which became the Francis Crick Institute in 2015. Professor Ley joined the Department of Medicine at Imperial College London in 2018.
Professor Ley’s group researches the regulation and function of specific NF-kB and MAP kinase signalling pathways in inflammation and immunity. One of his key discoveries was the demonstration that activation of the MAP 3-kinase TPL-2 is controlled by the IkB kinase (IKK) complex. This work shows that activation of the ERK1 and ERK2 MAP kinases is directly linked to activation of NF-kB transcription factors during inflammatory responses. He has also shown that IKK-induced proteolysis of NF-kB1 p105 has essential cell-intrinsic roles in T and B cells in adaptive immune responses.
Professor Ley’s group is currently investigating how TPL-2 stimulation of phagosome maturation in macrophages promotes the killing of pathogenic bacteria. In collaboration with Professor Anne Bowcock (Mt. Sinai, New York, USA), his group is also researching how the adaptor protein CARD14 activates NF-kB to trigger inflammation in the skin. Mutations in the gene encoding CARD14 lead to a high risk of developing psoriasis and psoriatic arthritis.
et al., 2021, TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria, EMBO Journal, Vol:40, ISSN:0261-4189, Pages:1-19
et al., 2020, CARD14(E138A) signalling in keratinocytes induces TNF-dependent skin and systemic inflammation, Elife, Vol:9, ISSN:2050-084X
et al., 2018, A20-binding inhibitor of NF-kappa B (ABIN) 2 negatively regulates allergic airway inflammation, Journal of Experimental Medicine, Vol:215, ISSN:0022-1007, Pages:2737-2747
et al., 2017, Tumor progression locus 2 reduces severe allergic airway inflammation by inhibiting Ccl24 production in dendritic cells, Journal of Allergy and Clinical Immunology, Vol:139, ISSN:0091-6749, Pages:655-666.e7
et al., 2016, Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation, Biochemical Journal, Vol:473, ISSN:1470-8728, Pages:1759-1768
et al., 2014, IKK-induced NF-kappa B1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen, Journal of Experimental Medicine, Vol:211, ISSN:0022-1007, Pages:2085-2101
et al., 2014, IκB kinase-induced interaction of TPL-2 kinase with 14-3-3 is essential for Toll-like receptor activation of ERK-1 and -2 MAP kinases, Proceedings of the National Academy of Sciences of the United States of America, Vol:111, ISSN:0027-8424, Pages:E2394-E2403
Arthur JSC, Ley SC, 2013, Mitogen-activated protein kinases in innate immunity., Nat Rev Immunol, Vol:13, Pages:679-692
et al., 2012, Coordinate regulation of TPL-2 and NF-κB signaling in macrophages by NF-κB1 p105., Mol Cell Biol, Vol:32, Pages:3438-3451