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| Cellular Immunology and Oncobiology |
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| Objectives |
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The researchers of the Cellular Immunology and Oncobiology group share common interests in identifying the cellular mechanisms that regulate the function of normal human cells and in understanding how disruption of these processes leads to disease, namely to allergic contact dermatitis, osteoarthritis, autoimmunity and cancer.
The researchers of the Cellular Immunology and Oncobiology group share common interests in identifying the cellular mechanisms that regulate the function of normal human cells and in understanding how disruption of these processes leads to disease, namely to allergic contact dermatitis, osteoarthritis, autoimmunity and cancer.
One of the strengths of this group is the variety of approaches, ranging from in vitro studies in human primary cell cultures and established cell lines, to in vivo experiments with animal models and analysis of clinical samples made in close collaboration with hospital clinical units, namely with the: i) Dermatology Department of the University Hospital of Coimbra (HUC); ii) Orthopaedic and Bone Bank Departments of HUC; iii) Clinical Hematology Department of HUC; iv) Portuguese Oncology Institute of Coimbra; v) Neuropathology Laboratory and Neurosurgery Service of HUC and vi) Center for Cancer Research of the Salamanca University, Spain.
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| RESEARCH ON CELLULAR IMMUNOLOGY FOCUSED IN: |
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Immunobiology of antigen presenting cells:
- to study modifications on the signalling profiles, cytokines and chemokines expression in dendritic cells induced by skin and respiratory chemicals to establish in vitro tests that can predict the sensitizing potential of chemicals.
- screening of lead molecules with anti-inflammatory properties obtained from medicinal plants.
Chondrocyte biology and osteoarthritis:
- characterizing the subunit composition of ATP-dependent K+ channels expressed in normal, aged and OA human chondrocytes and the role of high glucose in modulating their composition and 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 of CD38 in immune regulation, namely during mycobacterial infections and development of systemic autoimmunity.
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| RESEARCH ON ONCOBIOLOGY FOCUSED IN: |
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Cell signalling pathways involved in cancer and chemoresistance:
- to evaluate the role of oxidative stress and mitochondrial dysfunction and the deregulation of apoptotic and survival pathways that can allow the identification of new molecular therapeutic targets.
Pathways involved in thyroid and breast cancer:
- to investigate new players in thyroid and breast carcinogenesis, based on previously obtained clinical data which highlighted the possible role of LRP1B, a modulator of tumour microenvironment, and Claspin, a protein involved in checkpoint responses and DNA replication, as tumour suppressors in these two types of cancer, respectively.
Signaling pathways and genetic abnormalities in brain tumors:
- to evaluate chromosomal and genetic abnormalities involved in human gliomas and to identify new genes (and cell signaling pathways) potentially relevant for glioblastoma development and progression.
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MAIN ACHIEVEMENTS (2011)
RESEARCH ON CELLULAR IMMUNOLOGY |
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Immunobiology of antigen presenting cells:
We developed a dendritic cell-derived in vitro test to detect skin sensitizers. This test was protected through a patent and is currently ongoing validation by the European Center for the Validation of Alternative Methods.
Cymbopogon citratus has anti-inflammatory properties by inhibiting TNF-α and CCL5 production in macrophages through NF-κB, p38 MAPK and JNK pathways modulation. The suppression of NF-κB pathway by Cymbopogon citratus is mediated through inhibition of proteasome activity.
Chondrocyte biology and osteoarthritis:
In human chondrocytes, ATP-dependent potassium channels are composed of Kir6.1 and Kir6.2 pore forming subunits and SUR1 and SUR2B regulatory subunits, being involved in the regulation of the availability of glucose transporters.
One essential oil was found to inhibit catabolic and inflammatory responses in human chondrocytes, which is strongly predictive of potential anti-osteoarthritic activity. Although with lower potency, the same essential oil also inhibited inflammatory signalling pathways in a human intestinal epithelial cell line, suggesting potential activity in inflammatory bowel disease.
CD38 in immune function:
Using CD38KO mice, we found that CD38 is required for effective macrophage activation by T cells, NO production, chemotaxis and chemokine secretion during immune responses against mycobacteria; and for the control of systemic autoimmunity.
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| RESEARCH ON ONCOBIOLOGY |
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Cell signalling pathways involved in cancer and chemoresistance:
we found the involvement of oxidative stress and mitochondrial dysfunction in neoplastic development, as well as the levels of apoptotic modulators that can be related with the resistance to cell death. Our results also demonstrate that the farnesyltransferase inhibitor, a-HFPA, is effective independently of Ras mutations and that epigenetic modulators show a synergistic effect dependent on schedule of administration. Besides that, resistance to conventional chemotherapy and new targeted therapies is a problem and contribute to disease relapse.
Pathways involved in thyroid and breast cancer:
We unravelled a new pathway involved in non-medullary thyroid cancer involving LRP1B and the modulation of the extracelular microenvironment; we investigated the transforming potential of new RET mutations; and identified changes in Claspin associated with increased susceptibility to breast cancer and analysed the functional implications of these mutations in cell cycle regulation, namely in Chk1 activation.
Signaling pathways and genetic abnormalities in brain tumors:
The study of gliomas by iFISH revealed a complex cytogenetic heterogeneity and distinct clonal pathways of glioma evolution. In addition, the analysis of gene expression profile (GEP) demonstrated clear association between the GEP of gliomas and tumor histopathology and, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Regarding the cell signalling pathways, our results indicate that the activation of PI3K/Akt, MAP Kinase and CXCR4 signaling pathways may contribute to the chemoresistance that characterizes glioma cells.
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| Publications (2011) |
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| Group members |
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