Day 1 :
Autoimmunity Research Foundation, USA
Time : 10:05 AM
Trevor G Marshall graduated from the University of Adelaide, South Australia, in 1974. He taught at the Institute of Technology in Lae, Papua New Guinea, Curtin University and the University of Western Australia, before moving to California in 1982. His Doctoral thesis, ‘Insulin metabolism in Diabetes,’ was accepted by the University of Western Australia in 1985. He is currently Director of the Autoimmunity Research Foundation in California. He has won US FDA Rare Disease Designations for minocycline and clindamycin in the treatment of sarcoidosis. He is a Fellow of the European Association for Predictive, Preventive and Personalised Medicine (Brussels) and a member of the International Expert Council, Community of Practice: Preventative Medicine (Moscow).
Human biology, or at least the understanding of the complexity of human biology, has exponentiated since the turn of the century. Previously it was thought that the human Genome, or at least its Transcriptome subset, expressed around 20,000 proteins. Yet the Human Proteome is currently estimated to be between 250,000 and 1 million proteins. Add to that the 42,000 components of the human Metabolome which have already been identified, and the process of identifying clinically useful biomarkers is becoming very difficult indeed. Our focus has been on yet another level of complexity, the Microbiome, understanding its biomarker contribution by both transcriptional and post-translational mechanisms. While studying the action of microbiome components on the VDR Nuclear Receptor we came to realize that the biomarkers loosely called “Vitamin D” were actually steroid transcriptional-factors, rather than “vitamins.” When we published this it seemed as though the whole world had descended on our shoulders. Clinical Medicine just didn’t want to know that what it thought was a biomarker for health was actually a biomarker for disease. Even today, now that the prosective studies are coming in, few appreciate the complexity of properly interpreting the “Vitamin D” biomarkers. Here we propose that TNF-alpha is also a compromized biomarker. The discovery that TNF-alpha release in the spleen is controlled primarily by the brain, and that brain immune activity is affected by the electrosmog which nowadays surrounds us, necessarily changes the way that this biomarker needs to be studied and interpreted.
Institute of Genetics and Development of Rennes, France
Time : 10:35 AM
Claude Prigent is a Director of Research CNRS and Head of the Cell Cycle team, IGDR. He has been elected as an Associate Professor at the University Laval, Quebec, Canada. After completing his Post-doc in the DNA repair filed under the direction of Thomas Lindahl at the ICRF in London he has been working on mitosis trying to understand how this cell cycle stage was control by phosphorylation. He focused his activity on the Aurora-A kinase and cancer.
Aurora-A serine threonine kinase is a key player in cell cycle controls and essential for the progression through mitosis. It was found over-expressed in many human cancers. A gain of activity was proved to favour chromosome instability and carcinogenesis in mice. More importantly its over-expression was also reported to lead to resistance to drugs such as microtubule poisons used in chemotherapy. Additionally a loss of Aurora-A activity leads to uncontrolled stem cells proliferation at the origin of cancers in Drosophila and presumably in mice too. Aurora-A kinase has been a priority target for the development of inhibitors to be used in cancer treatment. Using a chemical-genetic approach, we investigated the effects of a specific inhibition of Aurora-A kinase during cell cycle progression, in particular during mitosis, in normal conditions but also in the presence of taxol or nocodazole. At the contrary to previous reports, we found that Aurora-A kinase activity was essential to arrest the cells in mitosis in response to taxol or nocodazol. An inhibition of Aurora-A in the presence of these drugs clearly leads to abortive mitosis, and formation of polyploidy cells.