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Understanding the effects of cyclo-oxygenase inhibition in the zebrafish

Millions of people worldwide use non-steroidal anti-inflammatory drugs (NSAIDs) to treat a wide variety of health conditions involving inflammation and pain In addition to their positive therapeutic effect, the use of NSAIDs, especially when long-term, is associated with an increased risk of adverse events in multiple organs/systems, including gastrointestinal and cardiovascular systems.

These pharmaceuticals act by inhibiting one or both isoforms of the enzyme cyclo-oxygenase (COX), which catalyse the synthesis of prostaglandins, chemicals that promote inflammation, pain, and fever. Major advances have been made in our understanding of NSAIDs pharmacology and toxicology; however, many aspects of the biological significance of COX inhibition still remain poorly understood. In this project, we will use the zebrafish as the experimental model to study the effects of NSAIDs on the immune and gastro-intestinal systems and will explore the interplay between the two responses.


Meet the Principal Investigator(s) for the project

Dr Luigi Margiotta-Casaluci - Luigi is a Lecturer in Pharmacology and Toxicology, and Group Leader in the Department of Life Sciences, Centre of Inflammation Research and Translational Medicine. He is specialised in the quantitative bi-directional extrapolation of complex biological processes between zebrafish, pre-clinical mammalian species, and humans. His research focuses on understanding the multi-scale effects of pharmaceuticals, alone and in combination, and developing predictive models able to support drug safety assessment. In parallel with the drug safety research, Luigi is also interested in understanding the molecular mechanisms underlying specific behavioural phenotypes. The Margiotta-Casaluci Lab is currently using the zebrafish model to study the effects of chronic inflammation on brain and behaviour. This research aims at generating novel mechanistic understanding that can potentially support the identification of more effective therapeutic strategies for patients affected by behavioural disorders. Since starting his independent group in 2015, Luigi secured external research funding as Principal Investigator from several public research councils (e.g. BBSRC, NC3Rs, European Commission) as well as industrial partners (e.g. AstraZeneca). His current research includes the following projects:  (2017-2021; BBSRC/AstraZeneca): Understanding molecular and phenotypic effects of cyclo-oxygenase inhibition in the zebrafish model.  (2017-2018; NC3Rs): Development of an Adverse Outcome Pathway for cardiotoxicity mediated by the blockade of L-type calcium channels.  (2018-2021; Brunel Isambard Award): Understanding the effects of chronic inflammation on brain and behaviour.  (2019-2022; H2020 European Commission): GOLIATH: Generation of novel, integrated and internationally harmonised approaches for testing chemical-induced metabolic disruption. Career 2020-to date: Group Leader & Lecturer, Pharmacology & Toxicology, College of Health and Life Sciences, Brunel University London, UK 2018-2020: Group Leader & Research Fellow II, Comparative Pharmacology & Toxicology, College of Health and Life Sciences, Brunel University London, UK 2015-2018: Group Leader & Research Fellow, Comparative Pharmacology & Toxicology, College of Health and Life Sciences, Brunel University London, UK 2011-2013: Visiting Scientist, AstraZeneca, UK 2011-2015: Post-doctoral Research Fellow, AstraZenenca/Brunel University London, London, UK (funded by BBSRC/AstraZeneca). Education 2007–2011: Ph.D. in Environmental Toxicology, Brunel University London, London, UK (supported by GlaxoSmithKline) 2003-2005: MSc Marine Biology, Universita’ Politecnica delle Marche, Ancona, Italy 2000-2003: BSc Biological Sciences, Universita’ Politecnica delle Marche, Ancona, Italy

Related Research Group(s)

Inflammation Research and Translational Medicine

Inflammation Research and Translational Medicine - Interdisciplinary research into understanding the inflammatory and immune processes that underlie human health, disease and healing.


Project last modified 18/06/2021