Dr Giovanni Yochanan Di Veroli
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Dr Giovanni Yochanan Di Veroli is pleased to consider applications from prospective PhD students.
Cancer, DNA Damage, signaling network, mathematics and synergy: what is the connection? Paradoxically, defective cell response to DNA damage has a major role not only in tumorigenesis but also cancer treatment. Many therapeutic approaches involve genotoxic compounds and it is partly the capacity of a cancerous cell to address the induced insult that determines its fate and therapy success. Cancer cells response to genotoxic insult can be quite different from normal cells as they present defective DNA integrity checkpoints and repair mechanisms which allow them to proliferate unrestrictedly. Cancer cells often proceed to a rewiring of their internal signalling dynamics, eventually relying on modified, non-physiological pathways (a process which has also been termed pathway ?addiction?). This restructuration may lead to inherent weaknesses which can be exploited. This is the rationale behind new therapeutic approaches that target cancer by disrupting signalling pathways differentially activated between cancer and normal cells. In order to develop this strategy, our group investigates innovative drug combinations. To find the right target is not straightforward: prior to the investigation of specific combinations, it requires a good understanding of the underlying dynamics that drive protein signalling. We attempt to develop this understanding by deriving new experimental protocols and employing various mathematical approaches. Once new combinations are identified, a proper estimation of its potential is required, often based on the quantification of drug synergy. In this respect we develop appropriate quantification approaches to assess combinations in vitro. Along the drug discovery process, this initial effort is later completed by a more thorough investigation of drug efficacy and toxicity for which additional efforts in term of experimental design and modelling are also needed. Thus we are also interested in supporting in vivo and clinical research using various mathematical tools.
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Di Veroli, G.Y., Davies M.R., Zhang H., Abi-Gerge N., Boyett M.R (2013). hERG inhibitors with similar potency but different binding kinetics do not pose the same proarrhythmic risk: implications for drug safety assessment. Journal of Cardiovascular Electrophysiology, 25: 197?207 Di Veroli, G. Y., Davies, M. R., Zhang, H., Abi-Gerges, N., & Boyett, M. R. (2012). High-throughput screening of drug-binding dynamics to HERG improves early drug safety assessment. American Journal of Physiology - Heart and Circulatory Physiology, 304(1), H104-H117 Di Veroli, G.Y., Rigopoulos, S. (2011). Modeling of aerosol formation in a turbulent jet with the transported population balance equation-probability density function approach. Physics of Fluids, 23(4) Di Veroli, G.Y., Rigopoulos, S. (2010). Modelling of Turbulent Precipitation: A Population Balance-Transported PDF Method. AIChE Journal, 56(4), 878-892.