Retecna: Network of Technological Centres in Navarra

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CIMA - Centre of apllied medican research

CIMA - CENTRE FOR APPLIED MEDICAL RESEARCH
Avda. Pío XII, 55. 31008 Pamplona
Tel.: 948 194 700 | Fax: 948 194 713 | E-mail: cima@unav.es
Contact: Fernando de la Puente - Managing Director

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The Centre for Applied Medical Research (CIMA) is managed by the Foundation for Applied Medical Research (FIMA) and promoted in cooperation with the University of Navarre.

The main activities of the centre are divided into the following divisions:

1. Hepatology and Gene Therapy Division

The research lines are focused on the development of new modes of gene therapy for viral hepatitis, cirrhosis of the liver and primitive and metastasic liver tumours (carcinoma of the colon and pancreas mainly).

• Innovation of vectors for gene therapy.
• Cancer of the liver:
  • Gene therapy in cancer of the liver.
  • Molecular mechanisms involved in the development of cirrhosis of the liver and in its development into a liver carcinoma.
• Viral hepatitis (hepatitis B and C):
  • Gene therapy development of antiviral strategies aimed at fostering humoral and cellular immune responses through genetic immunisation or vaccination and genetic immunotherapy.
  • Experimental model of hepatitis C in tupaias.
  • Type I interferon system in chronic HCV infections
• Immunomodulation and induction of humoral immune and Cytotoxic T Lymphocyte (CTL) responses in treating cancer and viral hepatitis.
• Other liver disorders:
  • Ethiopathogenia of primary spleen cirrhosis of the liver: genetic characterisation and expression of isoforms of anionic exchangers (AE).
  • Alteration of the production of inositol phosphoglycans (IPGs) and their implication in the physiopathology of liver failure.
  • Role of the TGFbeta in liver fibrosis mechanisms. Antifibrogenic effect of antagonists of the receptors of TGFbeta.
  • Hepatoprotective and antifibrogenic effects of IGF-I strategies in gene therapy based on IGF-I for the treatment of cirrhosis of the liver.

2. Cardiovascular sciences division

The main research lines in this division are arterial hypertension, aterosclerosis, and thrombosis, as they constitute the main cardiovascular risk factors and one of the main causes of morbi-mortality in Spain and the world.

• Arterial hypertension:
  • The genetic bases for oxidative vascular stress in hypertension.
  • Genomic and proteomics of the myocardium in hypertensive cardiopathy.
  • Diagnostic markers of cardiac lesion-dysfunction in hypertension.
• Aterotrombosis:
  • Clinical inflammation markers in cardiovascular risk stratification.
  • Fibrinolytic / proteolytic balance in human aterosclerotic lesions.
  • The role of inflammatory intercommunication / metabolic changes in aterosclerosis.
  • Modulation of the anticoagulant and anti-inflammatory systems by the endothelial protein C receptor (EPCR).
  • Modulation of the fibrinolytic system by protein C and its endothelial receptor.
  • Pharmacogenomics of oral anticoagulants.
• Thrombosis and Hemostasis:
  • Modulation of the anticoagulant and anti-inflammatory systems by the endothelial protein C receptor (EPCR).
  • Modulation of the fibrinolytic system by protein C and its endothelial receptor.
  • Pharmacogenomics of oral anticoagulants.

3. Neuroscience research

The main research lines are focused on diseases that exhibit dementia as their main symptom (Alzheimer's disease (AD) and related diseases, such as Lewy body dementia (DCL)) and diseases that exhibit movement disorders (Parkinson's disease (PD), multisystem atrophy (MSA) and idiopathic gait disorder of the elderly).

Basic research

• Transgenic mice as experimental models for neurodegenerative pathologies.
• Connectivity of basal ganglia in neurodegeneration.
• Neurodegenerative disorder pharmacology:
  • Development of new serotonergic drugs for the treatment of memory loss and other cognitive deficits.
  • Effect of a selective antagonist of the NRB2 subunit of the NMDA receptor on dyskinesias induced with levodopa in monkeys treated with MPTP.
• Mechanisms of trafficking and localisation of NMDA receptors in the neuron and in the sinaptic compartment. Endo/exocitic NMDA receptor trafficking control by mapped molecular signals. Validation of the neuroprotective and synaptic plasticity regulatory capacity of NR3 subunit.
• Immunology of neurodegeneration:
  • Inflammation, apoptosis and neurodegeneration: implications for the treatment of Parkinson’s disease.
  • T Lymphocyte therapy for neurological diseases.
  • Development of agonists of the receptors of the nerve growth factor: TrkA and P75, for the treatment of neurodegenerative diseases using combinatorial chemistry.
• Neurotrophic factors to halt and correct neurodegeneration. Analysis of the neurotrophic and neuroprotective activity of the pigment epithelium-derived factor (PEDF). Development of new strategies in administering neurotrophic factors.
• Cellular therapy of neurodegeneration. Implementation of adult carotid body cells and stem cells in basal ganglia of rats and primates.

Basic clinical research

• Early diagnosis of Alzheimer’s disease:
  • Identification of predictive markers of the progression from light cognitive deterioration to Alzheimer’s disease dementia in a prospective series.
  • Evaluation of the usefulness of the PET with 18F-FDG in the diagnosis of Alzheimer’s type dementia in a retrospective series.
• Progression markers and therapeutical response in Parkinson’s disease and idiopathic gait disorder of the elderly (IGDE):
  • Beginning and progression of Parkinson’s disease: seeking new therapeutical targets.
  • Effectiveness of bilateral stimulation of the subthalamic nucleus versus continuous infusion of apomorphine in patients with advanced Parkinson’s disease.
  • Affectation of striation as a cause of idiopathic gait disorder of the elderly.

4. Oncology division

Carcinogenesis

• Biomarkers:
  • Autocrine and paracrine regulation growth circuits in lung cancer.
  • mRNA processing proteins as early detection markers.
  • Use of microarray technology for the evaluation of differential genetic expression epithelial carcinogenesis.
  • Evaluation of the diagnostic usefulness of the molecules involved in pulmonary carcinogenesis and validation of new markers.
  • Combination of molecular analysis of biological samples and computerised axial tomography as a screening tool for the early detection of lung cancer. Optimisation of the analysis of sputum and washing markers.
  • FICTION technology for molecular tests of samples of sputum and bronchial washings in the context of protocols for early detection of lung cancer
• New therapeutical targets:
  • MAPK and phosphatases in lung carcinogenesis.
  • MEK and ERK inhibitors in lung carcinogenesis.
  • Identification of molecular targets in bone tumours.
• Adhesion, tumoral microenvironment and metastasis:
  • Adhesion molecules in epithelial-mesenchyme transition in the progression of cancer.
  • Metalloproteases and progression in lung cancer.
  • Genetic expression profile in the activation of cells fed in the tumoral microenvironment.
  • Lymphangiogenesis in lung cancer.

Cancer Immunotherapy and Cell Therapy

• Immunotherapy group: lymphomas and myelomas:
  • Anti-idiotype vaccination against lymphomas and myelomas.
  • Comparative studies on the efficiency of idiotype vaccinations in murine lymphomas and myelomas.
• Myeloproliferative syndromes/chronic myeloid leukaemia:
  • Resistance mechanisms and development of new targets.
• Study and therapeutical use of bone marrow multipotential stem cells (MAPC). In vitro isolation and differentiation of MAPCs.
• Development and analysis of therapeutic pre-clinical models of mantle lymphoma: validation of anti-cyclin D1 therapies in human and murine cell lines. Identification of new suppressor genes in lymphoma B in regions of homozigotic deletion. Caracterization of the genomic deletion of chromosome 11q in breast cancer.

Cancer genomics and pharmacogenomics

• Cancer pharmacogenomics group:
  • Gene expression profiles associated to chemoresistance in breast cancer.
  • Pharmacogenomic expression in metastasic cancer of the colon using microarray technology.

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