Dr Gloria Lopez-Castejon
Gloria Lopez-Castejon – Research summary
Deubiquitinases and inflammasome
Understanding the key processes and function of the immune system is fundamental to our understanding of health, well-being, and disease. Macrophages are vital cells regulating the immune response. They sense tissue damage or infection, and initiate key inflammatory processes such as the activation of the inflammasome, a molecular complex whose assembly leads to the release of pro-inflammatory cytokines. Inappropriate activation of macrophages and the inflammasome contributes to deleterious inflammatory syndromes including periodic fever syndromes, diabetes, atherosclerosis and Alzheimer’s disease. However our understanding of the regulatory mechanisms of inflammasome activation is incomplete thus hindering development of effective interventions for these devastating conditions.
With my research I aim to elucidate mechanisms that control inflammasome activation during an inflammatory response. I have recently shown that deubiquitinases (DUBs), enzymes that remove ubiquitin from proteins, are required for the activation of the inflammasome and the release of the proinflammatory cytokine IL-1beta. So far only a candidate DUB involved in this process has been identified, despite evidence suggesting the involvement of more than one, and how these proteases regulate the inflammasome still remains unknown. My research will study how DUBs are regulated in health and disease, especially in macrophages and how these enzymes contribute to the activation of the inflammasome.
Extracellular actin in inflammation
Necrosis can lead to an accumulation of actin in the extracellular environment that can be detrimental for the body and that can be removed from the circulation by an actin-scavenger system. We have observed that inflammasome mediated cell death leads to the release of actin to the extracellular environment and this is also mediated by DUBs. How actin contributes to the progression of inflammation and how the scavenger system is regulated during disease is not clear. I am investigating the role of actin as a of pro-inflammatory mediator and how actin and its scavenger-system influence the inflammatory response.
Gloria Lopez-Castejon – People
Gloria Lopez-Castejon – People
Jeremy Griggs - GSK
Matthew Sleeman - MedImmune/AstraZeneca
Paul French - Imperial College London
Rajesh Chopra - Celgene
Gloria López Castejón completed her PhD studying the mechanisms of interleukin-1beta secretion in teleost fish at the University of Murcia, Spain in 2007 under the supervision of Prof. Victoriano Mulero Mendez. The same year she joined the University of Manchester as a post-doctoral research associate where she continued her studies on IL-1beta secretion and inflammasome activation in mammalian systems, first under the supervision of Prof. Annmarie Surprenant and later under the supervision of Dr David Brough. In December 2012 she was awarded an MCCIR Post-doctoral Price fellowship to join the Manchester Collaborative Centre for Inflammation Research (MCCIR).
- Lopez-Castejon G, Luheshi NM, Compan V, High S, Whitehead RC, Flitsch S, Kirov A, Prudovsky I, Swanton E, Brough D (2013). Deubiquitinases Regulate the Activity of Caspase-1 and Interleukin-1ß Secretion via Assembly of the Inflammasome. J Biol Chem. 288(4):2721-33.
- Compan V, Baroja-Mazo A, López-Castejón G, Gomez AI, Martínez CM, Angosto D, Montero MT, Herranz AS, Bazán E, Reimers D, Mulero V, Pelegrín P (2012). Cell volume regulation modulates NLRP3 inflammasome activation. Immunity. 37(3):487-500.
- López-Castejón G, Corbett D, Roberts IS, Brough D (2012). Inhibition of Calpain blocks the phagosomal escape of Listeria monocytogenes. PLOS One. April; 7(4):e35936.
- Luheshi NM, Giles JA, López-Castejón G, Brough D (2011). Sphingosine regulates the NLRP3-inflammasome and IL-1ß release from macrophages. Eur J Immunol. Mar; 42(3); 716-25.
- Lopez-Castejón G, Baroja-Mazo A, Pelegrín P (2011). Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules. Cell Mol Life Sci. 68(18):3095-107.
- López-Castejón G, Theaker J, Pelegrin P, Clifton A, Braddock M and Surprenant A (2010). P2X7 receptor-mediated release of cathepsins from macrophages is a cytokine-independent mechanism potentially involved in joint diseases. J Immunol, Aug 15; 185(4):2611-9