Dr Lisa Mullen

Research

Lisa’s research interests are in inflammation and innate immunity, particularly in the context of auto-immune diseases such as Rheumatoid arthritis and Multiple Sclerosis.  She has a particular interest in cytokine biology and the role(s) of these proteins in the generation and resolution of inflammation. There are two major strands to Lisa’s current research: 1. Understanding the role of oxidative stress and redox regulation in sustaining chronic inflammation in autoimmune disease and 2. Development of engineered cytokines and enzymes as novel therapies for chronic inflammatory disease.

Oxidative stress, redox regulation and inflammation

Inflammation is often associated with oxidative stress (an imbalance between production of reactive oxygen species (ROS), and their elimination by antioxidants). Although redox "imbalance" can result in ROS-dependent pathology, it is also essential in the regulation of signalling pathways. Research on this topic is focused on identifying redox-regulated signalling molecules that are released under inflammatory conditions and elucidating the role of these molecules in chronic inflammatory disease and on the mechanisms by which ROS might activate inflammatory responses.

Development of engineered cytokines and enzymes as therapeutics

Cytokines play a central role in health and disease and as such, have long been recognised for their potential as therapeutics. However, cytokines have a remarkably complex biology and several of their biological attributes have traditionally hampered attempts to use these proteins in therapeutic settings. Latent cytokines are engineered using a naturally-occurring ‘shell’ structure known as the latency-associated peptide (LAP) from the cytokine transforming growth factor-β (TGF-β). These engineered molecules are designed to be released from their protective LAP shell only at the sites of disease to increase the half-life in the circulation and avoid side-effects. This delivery technology has potentially wide clinical applications in autoimmune conditions, inflammation, atherosclerosis and cancer and is being applied to enzymes as well as cytokines.

Selected publications

Mullen L, Seavill M, Hammouz R, Bottazzi B, Chan P, Vaudry D et al. Development of ‘Redox Arrays’ for identifying novel glutathionylated proteins in the secretome. Sci Rep. 2015;5:14630.

Mullen L, Chamberlain G, Sacre S. Pattern recognition receptors as potential therapeutic targets in inflammatory rheumatic disease. Arthritis Res Ther. 2015;17(1).

Salzano S, Checconi P, Hanschmann E, Lillig C, Bowler L, Chan P et al. Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proceedings of the National Academy of Sciences. 2014;111(33):12157-12162.

Mullen L, Rigby A, Sclanders M, Adams G, Mittal G, Colston J et al. Latency can be conferred to a variety of cytokines by fusion with latency-associated peptide from TGF-β. Expert Opinion on Drug Delivery. 2014;11(1):5-16.

Mullen L, Adams G, Layward L, Vessillier S, Annenkov A, Mittal G et al. Latent cytokines for targeted therapy of inflammatory disorders. Expert Opinion on Drug Delivery. 2014;11(1):101-110.

Koutsokeras A, Purkayastha N, Rigby A, Subang M, Sclanders M, Vessillier S et al. Generation of an efficiently secreted, cell penetrating NF-κB inhibitor. The FASEB Journal. 2013;28(1):373-381.

Mullen L, Adams G, Foster J, Vessillier S, Koster M, Hauser H et al. A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints. Annals of the Rheumatic Diseases. 2013;73(9):1728-1736.

Mullen L, Adams G, Chernajovsky Y. Increased disulphide dimer formation of latent associated peptide fusions of TGF-β by addition of l-cystine. Journal of Biotechnology. 2012;161(3):269-277.

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