Day 1 :
Institute of Bioengineering and Nanotechnology, Singapore
Time : 09:30-10:10
Daniele Zink earned her PhD from the University of Heidelberg, Germany in 1995 and completed her Habilitation (2001) at the Ludwig Maximilian University of Munich. In 2001, she was awarded funding of a Junior Group from the Volkswagen-Foundation, which she led until she moved to the Institute of Bioengineering and Nanotechnology (IBN) in Singapore in 2007. Her work on predictive in vitro models has been awarded by Merck Millipore and the US Society of Toxicology. She has won the prestigious LUSH Prize (2016, Science Category). She holds 10 patents/patent applications; is Editorial Board Member of Scientific Reports; has more than 70 peer reviewed publications and is Co-Founder and Director of the spin-off company Cellbae.
Evaluating the toxicity of chemicals, drug candidates and other compounds requires predictive methods. There is a steeply increasing demand for alternative methods due to various problems associated with animal experiments and changes in legislation (e.g. animal bans for cosmetics testing). However, many alternative methods are of unknown predictivity, and accepted alternative methods for predicting toxicity for human internal organs are not available. This problem is addressed by our work, which was initially focused on the kidney. Recently, we have developed the first animal-free platforms for the accurate prediction of nephrotoxicity in humans. These technologies have received various international awards, including the Lush Science Prize 2016. Our methods include the only available predictive methods based on human induced pluripotent stem cell-derived renal cells and a predictive high-throughput platform. The high-throughput platform is currently applied in collaboration with the US Environmental Protection Agency to predict the human nephrotoxicity of ToxCast compounds. The test balanced accuracies of our predictive methods range between ~80% - 90%, and these methods also reveal injury mechanisms and compound-induced cellular pathways. Based on a similar methodology we are now developing high-throughput platforms for predicting toxicity for other human organ systems, including liver and vasculature. Furthermore, we are establishing predictive organ-on-chip platforms for efficient repeated dose testing and dose-response assessment.
I Beritashvili Center of Experimental Biomedicine, Georgia
Time : 10:10-10:50
Merab Tsagareli is graduated from Tbilisi State University, Georgia (1977) and completed his PhD from Lomonosov State University of Moscow, Russia (1982) and then postdoctoral studies from Serbsky Research Institute for General and Forensic Psychiatry in Moscow, Russia (1985-1990). He is the Director of the Pain and Analgesia Laboratory at Ivane Beritashvili Center for Experimental Biomedicine in Tbilisi, Georgia. His research focuses on the behavioral studies of TRP channels and analgesic and tolerance effects of NSAIDs in relation with the descending pain modulation system. He has published more than 100 papers in peer-reviewed journals.
Transient receptor potential (TRP) cations channels are the largest group of sensory detector proteins expressed in the nerve terminals of many receptors including nociceptors and are activated by temperature and chemicals that elicit hot or cold sensations. Antagonists of these channels are likely promising targets for new analgesic drugs at the peripheral and central levels. Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we investigated whether three widely used NSAIDs (diclofenac, ketorolac, and xefocam) affect thermal and mechanical hyperalgesia following the activation of TRPA1 and TRPV1 channels. We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds bilaterally at various time points following intraplantar injection of the TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC) or the TRPV1 agonist capsaicin, or vehicle. When pretreated with vehicle, intraplantar injection of CA, AITC and capsaicin each resulted in significant decreases in thermal withdrawal latency and mechanical threshold in the ipsilateral hindpaw that did not return to baseline for more than 2 hr. To test effects of NSAIDS either diclofenac, ketorolac or xefocam was pre-injected in the same hindpaw 35 min prior to CA, AITC or capsaicin. Pretreatment with each of the three NSAIDs produced strong antinociceptive and antihyperalgesic effects lasting approximately 60 min. Thus, we show for the first time that local administration of NSAIDs suppresses thermal and mechanical hyperalgesia following TRPA1 or TRPV1 activation.
Acknowledgement: The work was supported partially by the grant from Shota Rustaveli National Science Foundation of Georgia (SRNSF #217076).