Dr Elisabete Silva

After graduating as a pharmacist in Portugal, I first became aware of endocrine disruption when I joined Prof. Kortenkamp’s group at the School of Pharmacy in London, as an Erasmus student in 1998. Since then, I have developed an interest in the effects of estrogens (both natural and man-made) and how exposure to such chemicals could have an impact on human health.

Currently, my research focuses on evaluating the effects of multi-component mixtures of estrogenic chemicals and their potential relationship with hormonal related diseases, in particular, breast cancer. I am interested in dissecting the mechanisms of action of steroidal estrogens and estrogen-like chemicals in breast development, carcinogenesis and tumour progression, in order to study the potential link between estrogenicity and cancer both at cellular and tissue level.

Qualifications

2009-2011: Postgraduate Certificate in Learning and Teaching. School of Hygiene and Tropical Medicine, University of London

1999–2003: PhD in Environmental Toxicology Thesis title: Understanding the mechanisms underlying the joint action of xenoestrogens. School of Pharmacy, University of London

1992–1998: Licenciatura in Pharmaceutical Sciences (Masters equivalent). First class degree. Faculty of Pharmacy, University of Porto, Portugal

Career

2011-present: Lecturer in Human Toxicology. Institute for the Environment, Brunel University

2007–2011: Lecturer in Toxicology. School of Pharmacy, University of London

2003–2007: Postdoctoral Research Fellow. School of Pharmacy, University of London

1999–2004: Teaching Assistant. School of Pharmacy, University of London

Research Interests

Research Activity

In the last 10 years, my main research interests were focused on addressing the hypothesis that the human total body burden of endocrine disrupters is implicated in hormone related diseases, such as breast cancer. Work addressing this issue was carried out during my PhD and postdoctoral fellowship (as part of the EU-funded project EDEN) and included predicting and assessing the estrogenic effects of multi-component mixtures of toxicants representative of human exposure, evaluating low-dose effects and determining combination effects of different classes of environmental contaminants (eg. pesticides and heavy metals).

Based on the observed interactions between estrogenic compounds, I developed a personal interest in the mechanisms of action of estrogens in the breast, and more specifically, in breast carcinogenesis. This interest has been reflected in my recent work on the effects of estrogens on growth factor signalling pathways and genomic instability. Since 2008, I have also been involved in developing and optimizing an in vitro system which recapitulates many of the features of the breast and allows the evaluation of potential neoplastic transformations of the mammary gland. By utilising this model, which involves three-dimensional cultures of immortalised breast cells, I am currently studying the effect of steroidal and environmental estrogens on breast glandular structure, morphogenesis and carcinogenesis in an effort to improve the understanding of hormonal carcinogenesis in estrogen receptor positive cancers. This model provides a valuable framework for the search of new diagnostic markers and therapeutic targets in epithelial cancers, especially in the specific cases of hormonal therapy resistance.

The past few years have provided substantial evidence that the microenvironment plays a very important role in breast maintenance, normal function and tumorigenesis. However, little attention has been given to the cells that are in close contact with the tumour from the onset, such as myoepithelial and epithelial cells present within the terminal lobular ductal units (TDLU) of the mammary gland. Do these cells play a part in breast cancer initiation and progression? In collaboration with Prof A. Kortenkamp, I am currently studying the cell-cell interaction and paracrine communication between normal and cancer cells within TDLUs in order to define mechanisms and identify potential target molecules, which could be used in the development of new therapeutic agents.

Building on my expertise on mixture assessment, in 2008, I started collaborating with Dr H Carmo, at the University of Porto, Portugal in a project in forensic toxicology studying the toxicological interactions between amphetamine designer drugs. In this work, the concepts previously utilised for the prediction and assessment of mixtures of environmental estrogens were applied to improve the understanding of the potential toxicological interactions between amphetamines, in the context of polydrug abuse.

Finally, I am also currently involved in a project in collaboration with Dr A Preto and Dr O Coutinho at the University of Minho, Portugal testing the anti-estrogenicity and cell toxicity of novel selective estrogen receptor modulators (SERMs) for potential use in breast cancer treatment.

Postgraduate researchers

Stephanie Marchese. 2008 – 2011. Development of novel in vitro three dimensional model for hormonal breast carcinogenesis

Diana Dias da Silva. 2009 – 2012. Study of the toxicological interactions between amphetamine designer drugs in the context of polydrug abuse

Maria Riverso. 2010 – 2013. Morphostats and the role of estrogens in mammary carcinogenesis (co-supervisor with Prof A Kortenkamp)

International teaching

2010–present: University of Minho, Portugal. International PhD Program on Molecular and Environmental Biology (PhD-MEB program), Module on Cancer and Cell Signalling. Subject: Hormonal carcinogenesis.

Member of the Society of Environmental Toxicology and Chemistry (SETAC).

Reviews articles for a number of journals including: Environmental Research, Environmental Toxicology and Pharmacology, International Journal of Andrology and Journal of Environmental Monitoring.

Publications

Journal Papers

(2013) Da Silva, DD., Carmo, H. and Silva, E., The risky cocktail: What combination effects can we expect between ecstasy and other amphetamines?, Archives of Toxicology 87 (1) : 111- 122

(2012) Marchese, S. and Silva, E., Disruption of 3D MCF-12A breast cell cultures by estrogens - An in vitro model for ER-mediated changes indicative of hormonal carcinogenesis, PLoS ONE 7 (10) : e45767 Download publication

(2011) Silva, E., Rajapakse, N., Scholze, M., Backhaus, T., Ermler, S. and Kortenkamp, A., Joint effects of heterogeneous estrogenic chemicals in the E-screen--exploring the applicability of concentration addition., Toxicol Sci 122 (2) : 383- 394 Download publication

(2010) Silva, D., Silva, E. and Carmo, H., What combination effects can we expect from amphetamine designer drugs?, TOXICOLOGY LETTERS 196 S148- S148

(2010) Silva, E., Kabil, A. and Kortenkamp, A., Cross-talk between non-genomic and genomic signalling pathways--distinct effect profiles of environmental estrogens., Toxicol Appl Pharmacol 245 (2) : 160- 170 Download publication

(2009) Lopez-Espinosa, M-J., Silva, E., Granada, A., Molina-Molina, J-M., Fernandez, MF., Aguilar-Garduno, C., Olea-Serrano, F., Kortenkamp, A. and Olea, N., Assessment of the total effective xenoestrogen burden in extracts of human placentas, BIOMARKERS 14 (5) : 271- 277

(2011) Modarai, M., Silva, E., Suter, A., Heinrich, M. and Kortenkamp, A., Safety of Herbal Medicinal Products: Echinacea and Selected Alkylamides Do Not Induce CYP3A4 mRNA Expression., Evid Based Complement Alternat Med 2011 213021- Download publication

(2008) Kabil, A., Silva, E. and Kortenkamp, A., Estrogens and genomic instability in human breast cancer cells--involvement of Src/Raf/Erk signaling in micronucleus formation by estrogenic chemicals., Carcinogenesis 29 (10) : 1862- 1868 Download publication

(2007) Silva, E., Scholze, M. and Kortenkamp, A., Activity of xenoestrogens at nanomolar concentrations in the E-Screen assay., Environ Health Perspect 115 Suppl 1 91- 97 Download publication

(2006) Silva, E., Lopez-Espinosa, MJ., Molina-Molina, JM., Fernández, M., Olea, N. and Kortenkamp, A., Lack of activity of cadmium in in vitro estrogenicity assays., Toxicol Appl Pharmacol 216 (1) : 20- 28 Download publication

(2004) Rajapakse, N., Silva, E., Scholze, M. and Kortenkamp, A., Deviation from additivity with estrogenic mixtures containing 4-nonylphenol and 4-tert-octylphenol detected in the E-SCREEN assay., Environ Sci Technol 38 (23) : 6343- 6352 Download publication

(2002) Silva, E., Rajapakse, N. and Kortenkamp, A., Something from "nothing"--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects., Environ Sci Technol 36 (8) : 1751- 1756 Download publication

(2002) Rajapakse, N., Silva, E. and Kortenkamp, A., Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action., Environ Health Perspect 110 (9) : 917- 921 Download publication

Conference Papers

(2009) da Silva, DD., Silva, R., Remiao, F., Carvalho, F., Bastos, MDL., Silva, E. and Carmo, H., Assessing combination effects of amphetamine designer drugs, 46th Congress of the European-Societies-of-Toxicology, TOXICOLOGY LETTERS (189) : S80- S80

(2011) Dias-da-Silva, D., Carmo, H. and Silva, E., Additive join effects between ecstasy and other amphetamine-type agents in primary cultured rat hepatocytes, 47th Congress of the European-Societies-of-Toxicology, TOXICOLOGY LETTERS (205) : S211- S211

(2009) Modarai, M., Silva, E., Suter, A., Heinrich, M. and Kortenkamp, A., The effects of Echinacea and its alkylamides on CYP3A4 transcriptional activity, 55th International Congress and Annual Meeting of the Society-for-Medicinal-Plant-Research-and-Natural-Product-Research, PLANTA MEDICA (75) : 998- 998