March 14, 2017 by Owen Green & Louise Youngs
Collating a plethora of international expertise, John Wambaugh (US EPA, US) and Nisha Sipes (NTP/NIEHS, US) chaired the ‘Fit for purpose: using computational models for risk’ workshop, which aimed to discuss the development, acceptance and use of computational models in risk assessment. Dr Owen Green attended the morning sessions, which included quantitative structure activity (QSAR) models for specific hazards and environmental fate, pharmacokinetic models of chemical disposition, toxicodynamic models for effect and exposure models. Supporting a number of product compliance services, Owen later participated in the workshop on ‘Modernizing toxicological risk assessment for compounds released from pharmaceutical, consumer, medical device and combination products: alternative tools and methods’. The potential toxicological effects of compounds released from medical devices and combination products are a patient safety concern for both device manufacturers and regulatory stakeholders. The session focussed on hazard and risk characterisation, providing further insight on Cramer classifications and a number of in silico tools.
Aiming to gain a greater understanding of the mechanistic pathways of disease and toxicology, Dr Louise Youngs attended a Symposium on ‘Translational control in disease progression and xenobiotic-mediated toxicity’. Following an introduction from Thomas Baker (Eli Lilly, US), Jenna Jewell (University of Texas, US) and Cheryl Walker (Baylor College of Medicine, US) outlined the mechanistic target of rapamycin (mTOR) pathways. Hyperactivation of the mTORC1 complex (mTOR, mLST8, Raptor, PRAS40, DEPTOR) is frequently observed in human disease, inhibitors of which are FDA approved for renal and breast cancer. The role of mTORC1 in protein synthesis, autophagy, lipid synthesis, organelle metabolism/biogenesis and cell cycle regulation were discussed. Dan Spandau (Indiana University School of Medicine, US) discussed the role of the integrated stress response (ISR) in atopic dermatitis and inflammation, discussing the roles of the endoplasmic reticulum (PERK, PKR), amino acid starvation, glucose deprivation, UVB irradiation (GCN2), hypoxia-ischaemia and iron deprivation (HRI) in adverse outcomes. To close the meeting, Jeffrey Willy (Eli Lilly, US) and Randal Kaufman (Sanford Burnham Prebys Medical Discovery School, US) outlined the role of the endoplasmic reticulum in driving the pathogenesis of liver disease.
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