Giulia Callegaro is postdoctoral researcher at the Division of Toxicology Biography: Giulia Callegaro obtained both her BSc and MSc degrees in Environmental Sciences and Technologies at the University of Milano-Bicocca (Italy). She completed her graduation with a Master project titled “Cell Transformation Assay for the prediction of chemicals’ carcinogenic potential: extraction and analysis of statistical image descriptors”. Directly after completing her studies in 2014 she started working as a PhD student at the University of Milano-Bicocca in the Environmental sciences department, on a project aiming at improving the prediction of the carcinogenic potential of chemicals, namely fostering the in vitro screening method called Cell Transformation Assay. During her PhD, she obtained the automation of the visual scoring through digital image analysis, and she contributed to the unravelling of the process of in vitro transformation by biochemically characterize the transformed clones obtained with CTA. Giulia defended her thesis in April 2017. From April 2017 till September 2017 she contributed as research fellow at the University of Milano-Bicocca to the project “The energetic metabolism role in the transformation process induced by cadmium”. Since December 2017 she is employed as a post-doctoral researcher at the Leiden University on a project aiming at establishing innovative methods to discover translational mechanistically relevant safety biomarkers for drug exposures. Her position if funded by the IMI eTRANSAFE project (http://etransafe.eu/). Project Drug-associated adversities, such as drug-induced liver injury, are a serious concern for patients, clinicians, and pharmaceutical companies, being the reason of many drug withdraws from the market. To achieve a better drug safety testing, research must work towards improving the understanding of the mechanisms of drug toxicity, while providing a context for the translation of such knowledge into different test organisms and humans. In this context, Giulia contributes to two main projects: 1) Safety assessment of anticancer kinase inhibitors: structure-based similarity approach and in vitro mechanistic assessment of induced-toxicity. While kinase inhibitors (KIs) are emerging as an important class of anti-cancer drugs, they still raise concerns for the several unwanted adverse effects in different organs and tissues. This project aims at evaluating KIs induced activations of cellular stress-pathways in BAC-HepG2 reporter cell lines for a large panel of KIs, while evaluating the possible role of off-target mechanisms. 2) Weighted gene co-regulated networks upon drug-induced perturbations: a powerful tool to investigate mechanisms of drug-induced adversities across different experimental systems. Toxicogenomic data in safety testing represents a challenging and promising source of data to characterize the mechanisms of drug-induced toxicities. Co-regulated gene network approaches can organize high dimensional toxicogenomic data, while not being biased by know biology, and help in identifying novel mechanisms and regulators of toxicity. We apply weighted gene co-expression network analysis (WGCNA) on the publicly available toxicogenomic datasets from different model systems, including primary human hepatocytes (PHH), rat in vivo liver and rat in vivo kidney.
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