Participant 8: Novartis
Novartis, Investigative Toxicology, Safety Profiling & Assessment, CH-4002 Basel, Switzerland
Participant leader: Prof. Armin Wolf
Relevant experience and laboratory resources
Novartis Pharma AG is a world wide leader in the field of applied In vitro Toxicology and plays an outstanding role among other industries. Beside standard in vitro test batteries for genotoxicity testing and in vitro teratogenicity testing Novartis continuously developed over the last 10 years an innovative and modern In vitro Toxicology facility in Basel with high degree of accumulated experience in different scientific areas. In vitro Toxicology successively improved by the implementation of modern state of the art in vitro technologies, which proved to be extremely valuable for explaining the mechanisms of adverse drug effects and for the in vitro screening at a very early phase of drug development. By the application of human cell and tissue cultures, it was possible to use in vitro data for the risk assessment in man.
Novartis establishing models comprise different level of complexity, ranging from whole perfused organs and cellular models to subcellular fractions for the most frequently affected toxicological target organs, liver, kidney and cardiovascular system from different species including man. Novel analytical tools, which depending on the project of interest were used ranged from confocal laser scanning microscopy, flow cytometry, NMR and pharmaco-genomical analyzes, like 2 D-gel electrophoresis, real time PCR and DNA chip array techniques. Beside these highly sophisticated tools, standard methods like HPLC and immunological assays like RIA and ELISA or electron microscopy are applied routinely.
About 30 people, including scientists and technical staff work currently in the In vitro Toxicology area. Continuous refreshing of the temporary staff by PhD students and postdocs from all over the world, guarantees Novartis a high degree of flexibility and an innovative environment.
Prof. Dr. Armin Wolf (M) is Head of Biochemistry within the Investigative Toxicology Department. Evaluation of test strategies to screen drug candidates for toxicity and to investigate mechanisms of toxicity is part of the daily business. In order to facilitate in vitro toxicity testing in Novartis drug development, the Cellomics and RNAi technologies were established. Armin Wolf is Professor of Toxicology at the University of Kaiserslautern (Germany) and Board certified Toxicologist (Fachtoxikologe DGPT) of the German Society of Pharmacology and Toxicology, Member of the Swiss Register of Toxicology and Certified Toxicologist of the European Society of Toxicology (EUROTOX).
Dr. Francois Pognan (M) is Global Section Head Biochemical & Molecular Toxicology in Novartis, where he supervises in vitro and in vivo mechanistic and investigative toxicology studies. One of the main goal of the section is to establish in vitro alternative models of toxicology, in which High Content Biology (HCB) has a prime importance. Prior to his current position, Francois Pognan was successively heading the Molecular and Cellular Toxicology laboratory in Pfizer France, from 1992 until 1997; then the Investigative Toxicology Group until 2000 in AstraZeneca UK. From that date, he was Associate Director of AZ North American Safety Assessment group, based in Delaware, and also Head of the Molecular and Investigative Toxicology Department until mid-2004. From this date to February 2007, he was Director of Molecular Toxicology in AstraZeneca UK. Since 1992, his entire focus has been the understanding of toxicity mechanisms and its direct application to toxicity assays as predictive tools for human drug side effects, using a variety of tools, ranging from biochemistry to gene profiling, including HCB. As such, he was one of the pioneer in HCB, using the very first version of the Cellomics ArrayScan™ equipment and published abstract and peer-reviewed paper on the design and realization of in vitro predictive assay for phospholipidosis using this platform, and several posters at international congresses about cholestasis assays based on HCB:
Dr. Min Dong (F) is the Labhead of Biochemistry in Investigative Toxicology at Novartis Pharma AG. She has strong expertises in performing biochemical investigations and developing in vitro models for toxicity testing. As techniques for high-content biology, she has been establishing Cellomics, LC-MS/MS and RNAi in her laboratory.
Dr. Olivier Grenet (M) is the head of Molecular Biology Group in Investigative Toxicology at Novartis Pharma AG. His strong expertise is in the area of real-time PCR (RT-PCR). He has established a RT-PCR technical platform for assessing biomarker genes in toxicity evaluation. His group actively engaged in the C-Path Predictive Safety Testing Consortium program and successfully established a panel of genomic biomarkers of nephrotoxicity.
Role of the participant in the project and main tasks
The participant is responsible for kidney cell cultures and analyzing their functional properties by means of High Content Imaging (Cellomics) and verifying pathways of toxicity by means of RNAi (WP2.1). Cellomics analysis will also be run for the cell culture models in WP2.2-2.5.