Post-doctoral Research Fellow
1. Predicting and testing the effects of human pharmaceuticals in fish
I am currently a Post-Doctoral Research Fellow at Brunel University (UK), with in depth-expertise in environmental toxicology of human pharmaceuticals.
My Ph.D. project at Brunel University, sponsored by GlaxoSmithKline, was focused on the integration of mammalian clinical and pre-clinical data with bioinformatics and modelling approaches, with the aim to predict the toxicity of pharmaceuticals in non-target species and hence guide the ecotoxicological approach.
In my current research project, I am testing the so-called “read-across” hypothesis, which states that human pharmaceuticals will cause the same effects in fish as they do in humans, and that they will do so at similar plasma concentrations. The project is supported by the British Biotechnology and Biological Sciences Research Council (BBSRC) and AstraZeneca.
2. Inter-species extrapolation of mammalian toxicological and pharmacological data
My interest in the development of predictive approaches to assess the effects of pharmaceuticals in non-target species does not end with fish. I am currently investigating the hypothesis that the read-across approach can be applied not only to fish, but also to any group of organisms that present a conserved and functional drug target, including invertebrates and plants.
To do so, I am using as reference pharmaceuticals the compound that I have been studying durring my Ph.D. project: the 5α-reductase inhibitor, dutasteride.
In my previous work, I studied the effects of dutasteride in fish (Margiotta-Casaluci et al., 2013). This pharmaceutical is used to treat benign prostatic hyperplasia, and acts by inhibiting the activity of the 5α-reductase, the enzyme that converts the testosterone into 5α-dihydrotestosterone.
The study of the evolutionary conservation of the target of dutasteride in fish revealed that the same target is also conserved in plants (DET2). The latter synthesise a specific class of steroid hormones, named “brassinosteroids”, which play, as in animals, major roles in many physiological processes, including growth and reproduction.
The high degree of functional similarity between mammalian 5α-reductase and plant DET2 suggests that both enzymes have similar in vivo biochemical functions and properties. I hypothesize that the human pharmaceutical dutasteride will elicit pharmacological effects in plants when it reaches tissue concentrations similar to the ones that produce an effect in humans. The inhibition of DET2 activity could affect plant growth, reproduction and light-adaptation.
This porject is supported by the Gen Foundation Award.
2013 - The Gen Foundation Award, Gen Foundation, London, UK.
Project: Effects of pharmaceuticals in the environment: the big jump from humans to plants.
Membership and affiliation
(2011) Ellis, T., Scott, A.P., Waring, C., Margiotta-Casaluci, L., Pottinger, T.G., Morris, S., Sumpter, J.P., Accuracy of methods of sex steroids determination. Defra, 28pp. http://nora.nerc.ac.uk/15247/
(2013) Margiotta-Casaluci, L., Relevance of the read-across approach to the Environmental Risk Assessment of pharmaceuticals. PHARMA Cluster International Conference. Pharmaceutical products in the environment: is there a problem?, 3-4 June 2013, Nimes, France.
(2012) Margiotta-Casaluci, L., Hannah, R., Sumpter, J.P., Mechanism of action of human pharmaceuticals in fish: the 5alpha-reductase inhibitor dutasteride as case study. 6th World Congress/22nd Annual Meeting of the Society of Environmental Toxicology and Chemistry (SETAC), Germany, Berlin.
Research interestsEnvironmental toxicology; Predicitve toxicology; In vitro to in vivo extrapolation; Comparative endocrinology; Pharmaceuticals in the environment.
Special Research Institute(s)
Huerta, B. , Margiotta-Casaluci, L. , Rodríguez-Mozaz, S. , Scholze, M. , et al. (2016) 'Anti-anxiety drugs and fish behavior: Establishing the link between internal concentrations of oxazepam and behavioral effects'. Environmental Toxicology and Chemistry. doi: 10.1002/etc.3448 Download publication
Margiotta-Casaluci, L. , Owen, SF. , Huerta, B. , Rodríguez-Mozaz, S. , et al. (2016) 'Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish'. Scientific Reports. doi: 10.1038/srep21978 Download publication
Runnalls, TJ. , Beresford, N. , Kugathas, S. , Margiotta-Casaluci, L. , et al. (2015) 'From single chemicals to mixtures-Reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow.'. Aquatic Toxicology, 169 pp. 152 - 167. doi: 10.1016/j.aquatox.2015.10.009 Download publication
Margiotta-Casaluci, L. , Owen, SF. , Cumming, RI. , De Polo, A. , et al. (2014) 'Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine'. PLoS One, 9 (10). doi: 10.1371/journal.pone.0110467 Download publication
De Polo, A. , Margiotta-Casaluci, L. , Lockyer, AE. and Scrimshaw, MD. (2014) 'A new role for carbonic anhydrase 2 in the response of fish to copper and osmotic stress: Implications for multi-stressor studies'. PLoS ONE, 9 (10). doi: 10.1371/journal.pone.0107707 Download publication
Caldwell, DJ. , Mastrocco, F. , Margiotta-Casaluci, L. and Brooks, BW. (2014) 'An integrated approach for prioritizing pharmaceuticals found in the environment for risk assessment, monitoring and advanced research'. Chemosphere. doi: 10.1016/j.chemosphere.2014.01.021
Sumpter, JP. and Margiotta-Casaluci, L. (2014) 'Are some invertebrates exquisitely sensitive to the human pharmaceutical Fluoxetine?'. AQUATIC TOXICOLOGY, 146 pp. 259 - 260. doi: 10.1016/j.aquatox.2013.11.021
Rand-Weaver, M. , Patel, A. , Margiotta-Casaluci, L. , Sumpter, JP. , et al. (2013) 'The read-across hypothesis and environmental risk assessment of pharmaceuticals'. Environmental Science and Technology, 47 (20). pp. 11384 - 11395. doi: 10.1021/es402065a Download publication
Margiotta-Casaluci, L. , Courant, F. , Antignac, J-P. , Le Bizec, B. and Sumpter, JP. (2013) 'Identification and quantification of 5 alpha-dihydrotestosterone in the teleost fathead minnow (Pimephales promelas) by gas chromatography-tandem mass spectrometry'. GENERAL AND COMPARATIVE ENDOCRINOLOGY, 191 pp. 202 - 209. doi: 10.1016/j.ygcen.2013.06.017
Margiotta-Casaluci, L. , Hannah, RE. and Sumpter, JP. (2013) 'Mode of action of human pharmaceuticals in fish: The effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study'. AQUATIC TOXICOLOGY, 128 pp. 113 - 123. doi: 10.1016/j.aquatox.2012.12.003
Brian, JV. , Beresford, N. , Margiotta-Casaluci, L. and Sumpter, JP. (2011) 'Preliminary data on the influence of rearing temperature on the growth and reproductive status of fathead minnows Pimephales promelas'. Journal of Fish Biology, 79 (1). pp. 80 - 88. doi: 10.1111/j.1095-8649.2011.02993.x Download publication
Margiotta-Casaluci, L. and Sumpter, JP. (2011) '5α-Dihydrotestosterone is a potent androgen in the fathead minnow (Pimephales promelas)'. General and Comparative Endocrinology, 171 (3). pp. 309 - 318.
Runnalls, TJ. , Margiotta-Casaluci, L. , Kugathas, S. and Sumpter, JP. (2010) 'Pharmaceuticals in the aquatic environment: Steroids and anti-steroids as high priorities for research'. Human and Ecological Risk Assessment, 16 (6). pp. 1318 - 1338. doi: 10.1080/10807039.2010.526503