Developments in in vitro genotoxicological assessment of nanomaterials
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Developments in in vitro genotoxicological assessment of nanomaterials
Wed, 10/11/2021 - 13:30 to 14:30
Location:
Speaker:
Shareen Doak
Affiliation:
Institute of Life Science, Swansea University Medical School,
Synopsis:
Despite great advances in nanosafety, technical challenges remain with the standard in vitro hazard evaluation strategies for nanomaterials. These tests are based on mammalian cells cultured as two dimensional (2D) monolayers, which do not closely mimic human physiology. However, cells cultured in three dimensions (3D), have increased structural complexity that is more representative of the in vivo environment. 3D tissue constructs and complex co-culture models incorporating multiple cell types, therefore, bridge the in vitro-to-in vivo gap for nanomaterial hazard assessment, potentially minimising animal testing. For example, co-culture models incorporating epithelial and macrophage cells can detect secondary genotoxicity, a key nanomaterial mode of action only detected in vivo. Additionally, 3D in vitro liver spheroids exhibit higher metabolic capacity, which is important for identifying pro-carcinogens. These models also support longer-term, repeated dosing, which is more representative of nanomaterial human exposure. Thus, advanced in vitro models for nanomaterial hazard assessment are supporting improved predictive toxicology.
Biography:
Shareen Doak is a Professor of Genotoxicology and Cancer at Swansea University Medical School where she leads the In Vitro Toxicology Group. Shareen is the UK and EUROTOX Registered Toxicologist, an invited Fellow of the Royal Society of Biology (FRSB) and an elected Fellow of the Learned Society of Wales (FLSW).
Shareen sits on the UK Government Committee on Mutagenicity (COM), and is the Nanomaterials Working Group Co-Leader for the International Genetic Toxicology Technical Committee (GTTC). She is also Editor-in-Chief for Mutagenesis. Shareen Coordinates the €13Million H2020 PATROLS project (www.patrols-h2020.eu) and is the Director of the €12Million Celtic Advanced Life Science Innovation Network (CALIN), an Ireland-Wales INTERREG operation established to build an innovation bridge between Wales and Ireland in life sciences (www.calin.wales).
Shareen’s research interests focus on the genotoxic profiles of engineered nanomaterials, the mechanisms underlying their DNA damaging potential and subsequent consequences upon human health. Her interests extend to the development of advanced 3D culture models and mechanism-based bioassays for safety assessment to reduce the need for animal testing. While her prostate cancer research focuses on understanding the molecular basis of progression to invasive, aggressive disease; with an ultimate aim of identifying a prognostic biomarker panel for improved clinical management of patients.