Margiotta-Casaluci Lab

 

Quantitative 

comparative 

pharmacology

 

Welcome to the

Margiotta-Casaluci Lab

The aim of our research is to understand and predict the causal link between the perturbation of biological  networks and the manifestation of adverse drug reactions. 

Our current research efforts are mainly focused to elucidate the role played by drug-mediated immune and inflammatory responses in determining drug efficacy and safety in both "normal" and pathological conditions.

In parallel with the drug 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 clinically relevant questions.

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 

 

Research Projects

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Modelling the cardiovascular effects of 

L-type calcium channel blockers

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Predicting 

chemical-induced perturbation of 

human metabolism

Read More
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Advancing the mechanistic understanding of

NSAIDs-mediated

effects 

Read More
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New strategies to support 

Adverse Outcome 

Pathway (AOP) 

development

Read More
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Shedding light on 

the link between inflammation 

and behaviour

Read More

Research Projects

heart-rate-1375324_1280.png

Modelling the cardiovascular effects of 

L-type calcium channel blockers

diabetes-1326964_640.png

Predicting 

chemical-induced perturbation of 

human metabolism

Network_Background_1 copy.jpg

Advancing the mechanistic understanding of

NSAIDs-mediated

effects 

brain-2062057_640.jpg

Shedding light on 

the link between inflammation 

and behaviour

Research Projects

heart-rate-1375324_1280.png

Modelling the cardiovascular effects of 

L-type calcium channel blockers

cell staining.jpeg

Development of
non-animal methods
to assess
chemical safety

Network_Background_1 copy.jpg

Advancing the mechanistic understanding of

NSAIDs-mediated

effects 

brain-3168269_1920.png

Network pharmacology 
approaches for the prediction of drug
mixture effects

Coming soon
brain-2062057_640.jpg

Shedding light on 

the link between inflammation 

and behaviour

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Genetic engineering

and zebrafish

disease

modelling

Coming soon
 

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 13-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

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LUIGI MARGIOTTA-CASALUCI, PhD

Group Leader, Principal Investigator 

Senior Lecturer in 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.

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BENJAMIN HOLMES

RESEARCH ASSOCIATE and  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. 

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PHILIP MARMON

PhD Candidate

Philip is PhD candidate, holding a 4-year BBSRC/AstraZeneca PhD studentship. His research is aimed at exploring the immune-mediated effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs, such as ibuprofen, diclofenac, celecoxib), and at characterising the phenotypic relevance of NSAIDs-target interaction networks, beyond cyclo-oxygenases (COXs) inhibition. Before joining the Margiotta-Casaluci Lab at Brunel University London, Philip graduated in Biomedical Sciences at the University of Sheffield (UK) and gained industry experience working at Oxford Immunotec. 

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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).

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CURRENT BSc and MSc INTERNS

BSc Final Year Projects and MSc Dissertations

Salwa Zabir (Biomedical and Molecular Sciences MSc)

Investigating the immunomodulatory effects of environmental chemicals  

Salwa is the recipient of a prestigious Matt Wilson Scholarship, which provides added-value to a research project by enabling costly experiments to be performed that otherwise would not be possible.

Matthew (“Matt”) Wilson studied at King’s College London and obtained an MSc in “Biomedical and Molecular Sciences Research” in October 2011. He graduated with Distinction, ranked 2nd of 33 students, notably whilst undergoing treatment for cancer throughout his studies. T

We are honoured to be the recipient of this Scholarship and we  are committed to carry out outstanding research and ensure that Matt’s legacy lives on!

Sebastian Millard (Analytical Toxicology MSc)

PK/PD of metformin across species 

Junyan Xu (Analytical Toxicology MSc)

Uptake and PK of phsycoactive drugs in zebrafish larvae 

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ALUMNI

Since 2016

  • Kreshma Aryaee

  • Isabelle Wetton

  • Aitana Alzugaray

  • Hanna Dusza (now at Utrecht University) ​

  • Shams Choudhury (now at MHRA)

  • Kiran Rakha

  • Joy Kayode

 

Get in touch

Dr Luigi Margiotta-Casaluci

Franklin-Wilkins Building - Room 4.125 

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 ​

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Publications

Google Scholar Profile

(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

(2020) The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.

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

(2020) Vision of a near future: Bridging the human health–environment divide. Toward an integrated strategy to understand mechanisms across species for chemical safety assessment.

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 10469​2. 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

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(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