Margiotta-Casaluci Lab
Mechanistic & Integrative
Toxicology
Welcome to the
Margiotta-Casaluci Lab
The aim of our research is to understand the mechanisms underlying chemical-induced toxicity and to develop innovative approaches able to predict with high accuracy the potential adverse effects of chemicals in both humans and wildlife.
Our current research efforts are mainly focused on understanding the effects of environmental chemicals and pharmaceuticals on immune functions and inflammatory responses, and characterising the involvement of those perturbations in the manifestation of chemical-induced or drug-induced adverse health effects.
In parallel with the drug and chemical safety research, we are also interested in understanding the molecular mechanisms underlying specific behavioural phenotypes. Specifically, we study the causal links between chronic inflammation, brain health, 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.
From a methodological perspective, we integrate computational biology approaches, network biology concepts, and the zebrafish model to investigate important research questions relevant to human and environmental health.
The Margiotta-Casaluci Lab is based at King's College London, School of Cancer and Pharmaceutical Sciences.
Funders
BBSRC
NC3Rs
European Commission
Brunel University London
AstraZeneca
Unilever
News
New lab member!
We are very happy to welcome Gian Hobbs, who has just started a new BBSRC-AstraZeneca PhD project in our lab. Gian will use a combination of novel high-content imaging methods to investigate the functional and phenotypic conservation of drug-mediated immune and inflammatory responses in zebrafish and humans.
We are hiring!
Fully funded 4-year BBSRC iCASE PhD position available in our lab (in collaboration with Unilever) Deadline 01 July 2023
Successful VIVA!
Congratulations to Ines Moreira for passing her PhD VIVA with minor corrections! Ines defended her PhD Thesis focused on the study of the effects of inflammation on animal behaviour. Thanks to Dr Matt Parker and Dr Ronan McCarthy for the rigorous and lively examination.
Research Projects
Network pharmacology
approaches for the prediction of drug
mixture effects
Consulting services
AOP development
We provide custom-tailored Adverse Outcome Pathway (AOP)-development to support the identification of effective mode-of-action-driven chemical testing strategies.
Chemical risk assessment
Thanks to our 17-year experience in mode-of-action toxicology, we can help you to decide cost-effective and scientifically sound strategies to facilitate the integration of advanced mechanistic considerations into the traditional environmental risk assessment (ERA) of pharmaceuticals and other chemicals. We also provide custom-made data visualisation strategies to facilitate inter-stakeholder communication and support regulatory decision-making.
Contact us for more details
Group members
LUIGI MARGIOTTA-CASALUCI, PhD
Group Leader, Principal Investigator
Senior Lecturer in Mechanistic & Integrative Toxicology
Luigi is a Senior Lecturer in Toxicology, and Group Leader at King's College London with more than 15 years of experience in the study of mode-of-action-driven toxicology of pharmaceuticals and cross-species extrapolation. He earned his PhD in Environmental Toxicology from Brunel University London in 2011 ( sponsored by GlaxoSmithKline), under the supervision of Professor John Sumpter OBE, working on the extrapolation of pharmacological and toxicological data between zebrafish, mammalian pre-clinical models, and humans. Luigi continued to develop his research interests in comparative pharmacology during a 4-year BBSRC/AstraZeneca-funded Post-Doc at AstraZeneca and Brunel University London, where he started his independent research group in 2015. In 2021, Luigi started a Senior Lecturer (Associate Professor) position at King's College London.
GIAN HOBBS
PhD Candidate
Gian is PhD candidate, holding a 4-year BBSRC/AstraZeneca PhD studentship. His research is aimed at exploring the phenotypic and functional conservation of drug-induced immune and inflammatory responses in zebrafish and human. Before joining the Margiotta-Casaluci Lab, Gian read Pharmacology and Innovative Therapeutics at Queen Mary University of London. After completing his BSc, he earned an MRes in Biomedical and Molecular Sciences at King's College London, where he gained research experience with the use of C. elegans as toxicology model.
BENJAMIN HOLMES
Data Scientist
Ben is data scientist and registered associate nutritionist interested in research areas such as human disease, nutrition, sports science and pharmacology. He joined the DEVINA team in January 2022, and since then he has been developing a novel and exciting data platform - integrated with intuitive data viz - that will become a reference tool for any stakeholder interested in the use of toxicity data to support regulatory decision making.
INES MOREIRA
PhD Candidate
Ines is PhD candidate, holding a 3-year Isambard PhD studentship. Her research is aimed at characterising the relationship between gut inflammation and behavioural disorders, bridging zebrafish research, human-relevant experimental data, and clinical observations. Ines graduated in Environmental Health at the Polytechnic Institute of Oporto (Portugal), and earned her master's in Toxicology And Risk Assessment from Brunel University London (UK).
ALUMNI
Since 2016
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Dr Philip Marmon - PhD (now Clinical Trial Manager II at Medpace)
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Dr Hanna Dusza - PhD (now Assistant Professor at Utrecht University)
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>10 other BSc and MSc interns since 2018
Get in touch
Dr Luigi Margiotta-Casaluci
Franklin-Wilkins Building - Room 3.77
King's College London
Department of Analytical, Environmental, & Forensic Sciences
School of Cancer & Pharmaceutical Sciences
Faculty of Medicine and Life Sciences
London
United Kingdom
M: under request
Publications
(2023) Cross‐species extrapolation of biological data to guide the environmental safety assessment of pharmaceuticals–The state of the art and future priorities.
Margiotta-Casaluci, L.; Owen, S.F.; Winter, MJ. Environmental Toxicology and Chemistry (In press). Link
(2023) Big Question to Developing Solutions: A Decade of Progress in the Development of Aquatic New Approach Methodologies from 2012 to 2022.
Langan, L.; Paparella, M.; Burden, N.; Constantine, L.; Margiotta-Casaluci, L.; Miller, T.H.; Jannnike Moe, S.; Owen. S.F.; Schaffert, A.; Sikanen, T. Environmental Toxicology and Chemistry (In press). Link
(2022) Environmental Occurrence and Predicted Pharmacological Risk to Freshwater Fish of over 200 Neuroactive Pharmaceuticals in Widespread Use.
Sumpter, J.P.; Margiotta-Casaluci, L. Toxics 10(5):233. Link
(2022) COVID-19 through adverse outcome pathways: Building networks to better understand the disease – 3rd CIAO AOP Design Workshop
Clerbaux, L-A.; (...) Margiotta-Casaluci, L.; (...) Wittwehr, C. ALTEX 39(2): 322-335. Link
(2022) Are synthetic glucocorticoids in the aquatic environment a risk to fish?
Hamilton, C.M; Winter, M.J.; Margiotta-Casaluci, L.; Owen, S.F.; Tyler, C.R. Environment International 162, 107163. Link
(2021) Pharmacology-informed prediction of the risk posed to fish by mixtures of non-steroidal anti-inflammatory drugs (NSAIDs) in the environment.
Marmon, P.; Owen, S.F.; Margiotta-Casaluci, L. Environment International 146, 106222. Link
(2020) New ideas for non-animal approaches to predict repeated-dose systemic toxicity: Report from an EPAA Blue Sky Workshop.
Mahony, C.; Ashton, R.S.; Birk, B.; Boobis, A.R.; Cull, T,; Daston, G.P.; Ewart, L.; Knudsen, T.B.; Manou, I.; Maurer-Stroh, S.; Margiotta-Casaluci, L.; Müller, B.P.; Nordlund, P.; Roberts, R.A.; Steger-Hartmann, T.; Vandenbossche, E.; Viants, M.R.; Vinken, M.; Cronin. Regulatory Pharmacology and Toxicology 114, 104668. Link
(2020) Toxicology advances for 21st century chemical pollution.
Brooks, B.W.; Sabo-Attwood, T.; Choi, K.; Kim, S.; Kostal, J.; LaLone, C.A.; Langan, L.M.; Margiotta-Casaluci, L.; You, J.; Zhang, X. One Earth 2:312-316. Link
Legler, J.; Zalko, D.; Jourdan, F.; Jacobs, M.; Fromenty, B.; Balaguer, P.; Bourguet, W.; Munic Kos, V.; Nadal, A.; Beausoleil, C.; Cristobal, S.; Remy, S.; Ermler, S.; Margiotta-Casaluci, L.; Griffin, J.L.; Blumberg, B.; Chesné, C.; Hoffmann, S.; Andersson, P.L.; Kamstra, J.H., on behalf of the GOLIATH Consortium; Int. J. Mol. Sci. 21, 3480. Link
Rivetti C; Allen TEH; Brown JB; Butler B; Carmichael PL; Colbourne JK; Dent M; Falciani F; Gunnarsson L; Gutsell S; Harrill JA; Hodges G; Jennings P; Judson R; Kienzler A; Margiotta-Casaluci L; Muller I; Owen SF; Rendal C; Russell PJ; Scott S; Sewell F; Shah I; Sorrel I; Viant MR; Westmoreland C; White A; Campos B. Toxicology in Vitro 104692. Link
(2020) Immunoassays are not immune to errors: examples from two studies of steroid output from freshwater trout farms.
Ellis T; Waring CP; Margiotta-Casaluci L; Pottinger TG; Morris S; Reese A; Sumpter JP; Scott AP. General and Comparative Endocrinology 285,113226. Link
(2019) Testing the translational power of the zebrafish: an inter-species analysis of responses to cardiovascular drugs.
Margiotta-Casaluci L; Owen SF; Rand-Weaver, M; Winter MJ. Frontiers in Pharmacology 10, 893. Link
(2019) Pharmacology beyond the patient – the environmental risk of human drugs.
Gunnarsson L; Snape J; Verbruggen B; Owen S; Kristiansson E; Margiotta-Casaluci L; Österlund T; Hutchinson K; Leverett D; Marks B; Tyler CR. Environment International 129,320-332. Link
(2019) Protecting the environment from psychoactive drugs: problems for regulators illustrated by the possible effects of tramadol on fish behaviour.
Tanoue R; Margiotta-Casaluci L; Huerta B; Runnalls TJ; Eguchi A; Nomiyama K; Kunisue T; Tanabe S; Sumpter JP. Science of the Total Environment 664,915-926. Link
(2018) Adverse Outcome Pathway Networks I: Development and Applications.
Knapen D; Angrish MM; Fortin MC; Katsiadaki I; Leonard M; Margiotta- Casaluci L; Munn S; O’Brien JM; Pollesch N; Smith C; Zhang X; Villeneuve DL. Environmental Toxicology and Chemistry 37,1723-1733. Link
(2018) Adverse Outcome Pathway Networks II: Network Analytics.
Villeneuve, D.L., Angrish, M.M., Fortin, M.C., Katsiadaki, I., Leonard, M., Margiotta-Casaluci, L., Munn, S., O’Brien, J.M., Pollesch, N., Smith, C., Zhang, X., Knapen, D. Environmental Toxicology and Chemistry 37,1734-1748. Link
(2017) Uptake and Metabolism of Human Pharmaceuticals by Fish—A Case Study with the Opioid Analgesic Tramadol.
Tanoue, R., Margiotta-Casaluci, L., Huerta, B., Runnalls, T.J., Nomiyama, K., Kunisue, T., Tanabe, S., Sumpter, J.P. Environmental Science and Technology 51,12825-12835. Link
(2016) Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish.
Margiotta-Casaluci, L., Owen, S.F., Huerta, B., Rodríguez-Mozaz, S., Kugathas, S., Barceló, D., Rand-Weaver, M., Sumpter, J.P. Scientific Reports 6. Link
(2016) Anti-anxiety drugs and fish behaviour: establishing the link between internal concentrations of oxazepam and behavioural effects.
Huerta, B., Margiotta-Casaluci, L., Rodríguez-Mozaz, S., Scholze, M., Winter, M.J., Barceló, D., Sumpter, J.P.
Environmental Toxicology and Chemistry 35(11),2782-2790. Link
(2015) From single chemicals to mixtures: reproductive effects of levonorgestrel and ethinylestradiol in the fathead minnow.
Runnalls, T.J.; Beresford, N.; Kugathas, S.; Margiotta-Casaluci, L.; Scholze, M.; Scott, A.P.; Sumpter, J.P. Aquatic Toxicology 169,152-167. Link
(2014) Quantitative cross-species extrapolation between humans and fish: the case of the anti-depressant fluoxetine.
Margiotta-Casaluci, L.; Owen S.F.; Cumming, R.I.; de Polo, A.; Winter, M.J.; Panter, G.H.; Rand-Weaver, M.; Sumpter, J.P. PLoS ONE 9 (10). Link
(2014) A new role of carbonic anhydrase II in the response of fish to copper and osmotic stress: implications for multi-stressor studies.
de Polo, A.; Margiotta-Casaluci, L.; Lockyer, A.E.; Scrimshaw, M.D. (2014) PLoS ONE 9 (10). Link
(2014) An integrated approach for prioritizing pharmaceuticals found in the environment for risk assessment.
Caldwell, D.J.; Mastrocco, F.; Margiotta-Casaluci, L.; Brooks, B.W. Chemosphere 115, 4-12. Link
(2014) Are some invertebrates exquisitely sensitive to the human pharmaceutical Fluoxetine?
Sumpter, J.P.; Margiotta-Casaluci, L. Aquatic Toxicology 146,259-260. Link
(2013) The Read-Across Hypothesis and Environmental Risk Assessment of Pharmaceuticals.
Rand-Weaver, M.; Margiotta-Casaluci, L.; Patel, A.; Panter, G.H.; Owen, S.F.; Sumpter, J.P. Environmental Science and Technology 47(20),11384–11395. Link
(2013) Mode of action of human pharmaceuticals in fish: The effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study.
Margiotta-Casaluci, L., Hannah, R.E., Sumpter, J.P. Aquatic Toxicology 128-129,113-123. Link
(2013) Identification and quantification of 5α-dihydrotestosterone in the teleost fathead minnow (Pimephales promelas) by gas chromatography-tandem mass spectrometry.
Margiotta-Casaluci, L.; Courant, F.; Antignac, J.P.; Le Bizec, B.; Sumpter, J.P. General and Comparative Endocrinology 191,202- 209. Link
(2011) Preliminary data on the influence of rearing temperature on the growth and reproductive status of fathead minnows (Pimephales promelas).
Brian, J.V., Beresford, N., Margiotta-Casaluci, L., Sumpter J.P. Journal of Fish Biology 79,80-88. Link
(2011) 5α-Dihydrotestosterone is a potent androgen in the fathead minnow (Pimephales promelas).
Margiotta-Casaluci, L., Sumpter, J.P. General and Comparative Endocrinology 171,309-318. Link
(2010) Pharmaceuticals in the aquatic environment: steroids and anti-steroids as high priorities for research.
Runnalls, T.J.*, Margiotta-Casaluci, L.*, Kugathas, S. and Sumpter, J.P. International Journal of Human and Ecological Risk Assessment 6,1318-1338. (*Co-first authorship). Link