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Biography |
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Yaqoub Ashhab was born and grew up in Hebron, Palestine. He received his undergraduate biology degree with First Class Honours from Middle East Technical University, Turkey in 1990. He received his M.Sc. and Ph.D. in Molecular Biology from Autonomous University of Barcelona in 1994 and 1998, respectively. During his work in the laboratory of Prof. Ricardo Pujol-Borrell, he investigated the CC chemokines gene family and their role in autoimmune thyroid disease. In 1999 he joined the laboratory of Prof. Dina Ben-Yehuda at Hadassah Medical Centre, Hebrew University to do his Postdoctoral research in the field of programmed cell death. During his postdoc, he discovered and characterized the BIRC7 gene that codes for a new member of the “Inhibitor of Apoptosis Proteins” family. From 2002-2004 he became a research associate in the same research centre. In 2004 he joined Palestine Polytechnic University in Hebron, Palestine to lead the establishment of the first biotechnology research unit that has been funded by the European Commission and the World Bank. He is currently Associate Professor of Molecular Biology and Director of Biotechnology Training and Research Unit. His main interest is to build a network for developing bioinformatics training and research models in developing countries. His two bioinformatics research areas are: studying the molecular mechanisms of programmed cell death, and investigating microbial genomics in order to develop novel diagnostics and vaccines.
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Abstract |
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SEARCHING FOR POTENTIAL ANTI-CANCER DRUG TARGETS USING IN SILICO FISHING APPROACHES
Apoptosis is a crucial biological process that prevents uncontrolled cell proliferation and eliminates harmful cells. The efficacy of most anticancer drugs is due to their ability to activate apoptosis. Unfortunately, the resistance of tumor cells to drug-induced apoptosis is emerging as a major category of cancer treatment failure. Therefore, there is an increasing interest in understanding apoptosis regulatory mechanisms.
In this talk, I will present two different bioinformatics approaches that we used to search for novel cellular factors that are involved in apoptosis regulation and execution. In the first approach, we used the human expressed sequence tags database (dbEST) to search for new anti-apoptotic factors. We identified and cloned a novel human inhibitor of apoptosis (IAP) gene that is designated BIRC7. The gene encodes for two isoforms, which we designated Livin-alpha and Livin-beta. Interestingly, the two splicing variants have different biological properties and tissue distribution pattern. In addition, we described a novel regulatory mechanism by which Livin is cleaved by caspase 3. Remarkably, the cleaved Livin does not only lose its antiapoptotic function but also gains a proapoptotic effect.
In the second approach we developed a bioinformatics system that can predict, with high accuracy, caspase 3 substrates. We used this in silico tool to screen for potential caspase 3 substrates in the complete human proteome from UniProtKB databases. Our preliminary analyses revealed the presence of hundreds of potential caspase-3 substrates that are not yet described. The majority of these proteins are involved in signal transduction, nucleic acid binding, integrity of cytoskeleton, regulation of cell adhesion, and immune response.
Identification and understanding the biological role of the factors that are involved in the initiation, regulation and execution of apoptosis are crucial to gain further insight into the cellular mechanisms that regulate apoptosis, survival and proliferation as well as other biological processes with implication to drug targeting.
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