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Annual Report of Activities CNC 2011 - Center for Neuroscience and ...

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Cellular Immunology <strong>and</strong> Oncobiology GroupHead: Celeste Lopes79The researchers <strong>of</strong> the Cellular Immunology <strong>and</strong> Oncobiology group share common interests in identifying the cellular mechanisms that regulate the function <strong>of</strong> normal human cells <strong>and</strong> in underst<strong>and</strong>ing how disruption <strong>of</strong> these processes leads to disease, namely to allergic contact dermatitis, osteoarthritis, autoimmunity <strong>and</strong> cancer. One <strong>of</strong> the strengths <strong>of</strong> this group is the variety <strong>of</strong> approaches, ranging from in vitro studies in human primary cell cultures <strong>and</strong> established cell lines, to in vivo experiments with animal models <strong>and</strong> analysis <strong>of</strong> clinical samples made in close collaboration with hospital clinical units, namely with the: i) Dermatology Department <strong>of</strong> the University Hospital <strong>of</strong> Coimbra (HUC); ii) Orthopaedic <strong>and</strong> Bone Bank Departments <strong>of</strong> HUC; iii) Clinical Hematology Department <strong>of</strong> HUC; iv) Portuguese Oncology Institute <strong>of</strong> Coimbra; v) Neuropathology Laboratory <strong>and</strong> Neurosurgery Service <strong>of</strong> HUC <strong>and</strong> vi) <strong>Center</strong> <strong>for</strong> Cancer Research <strong>of</strong> the Salamanca University, Spain. 1a) Research on Cellular Immunology focused in: Immunobiology <strong>of</strong> antigen presenting cells: -­‐ to study modifications on the signalling pr<strong>of</strong>iles, cytokines <strong>and</strong> chemokines expression in dendritic cells induced by skin <strong>and</strong> respiratory chemicals to establish in vitro tests that can predict the sensitizing potential <strong>of</strong> chemicals. -­‐ screening <strong>of</strong> lead molecules with anti-­‐inflammatory properties obtained from medicinal plants. Chondrocyte biology <strong>and</strong> osteoarthritis: -­‐ characterizing the subunit composition <strong>of</strong> ATP-­‐dependent K +channels expressed in normal, aged <strong>and</strong> OA human chondrocytes <strong>and</strong> the role <strong>of</strong> high glucose in modulating their composition <strong>and</strong> function. -­‐ identifying new compounds in plant volatile extracts with potential anti-­osteoarthritic activity, as well as with potential activity against other diseases with a chronic inflammatory component, namely inflammatory bowel disease. CD38 in immune function: -­‐ to study the role <strong>of</strong> CD38 in immune regulation, namely during mycobacterial infections <strong>and</strong> development <strong>of</strong> systemic autoimmunity. 1b) Research on Oncobiology focused in: Cell signalling pathways involved in cancer <strong>and</strong> chemoresistance: -­‐ to evaluate the role <strong>of</strong> oxidative stress <strong>and</strong> mitochondrial dysfunction <strong>and</strong> the deregulation <strong>of</strong> apoptotic <strong>and</strong> survival pathways that can allow the identification <strong>of</strong> new molecular therapeutic targets. Pathways involved in thyroid <strong>and</strong> breast cancer: -­‐ to investigate new players in thyroid <strong>and</strong> breast carcinogenesis, based on previously obtained clinical data which highlighted the possible role <strong>of</strong> LRP1B, a modulator <strong>of</strong> tumour microenvironment, <strong>and</strong> Claspin, a protein involved in checkpoint responses <strong>and</strong> DNA replication, as tumour suppressors in these two types <strong>of</strong> cancer, respectively. Signaling pathways <strong>and</strong> genetic abnormalities in brain tumors: -­‐ to evaluate chromosomal <strong>and</strong> genetic abnormalities involved in human gliomas <strong>and</strong> to identify new genes (<strong>and</strong> cell signaling pathways) potentially relevant <strong>for</strong> glioblastoma development <strong>and</strong> progression. Main Achievements 2a) Research on Cellular Immunology Immunobiology <strong>of</strong> antigen presenting cells: We developed a dendritic cell-­‐derived in vitro test to detect skin sensitizers. This test was protected through a patent <strong>and</strong> is currently ongoing validation by the European Centre <strong>for</strong> the Validation <strong>of</strong> Alternative Methods (ECVAM). We found that Cymbopogon citratus has anti-­‐inflammatory properties by

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