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Becas, ayudas y subvenciones
http://www.060.es/te_ayudamos_a/ayudas_becas_y_subvenciones/common/becas.pdf
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Se agradece la colaboración del:
Centro de Información Administrativa de Presidencia del Gobierno
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---Procedencia:
Institución:CNIC
Contacto correo-e:eisoininen@cnic.es
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Postdoctoral position
(Ref. IP62.01.2010)
The CNIC has a joint postdoctoral position available in the laboratories of Dr. Vicente Andrés and Andrés Hidalgo in the Department of Atherothrombosis and Cardiovascular Imaging to study the mechanisms underlying the formation and progression of the atherosclerotic plaque, including the trafficking of blood cells to lesion areas at the intravascular and intraplaque interfaces, as well as microvessels of the arterial wall. Multiple genetic, pharmacological and in vivo imaging techniques will be used to address this question in murine models. The recipient groups have extensive experience both in the study of atherosclerosis and in the use of imaging techniques to study inflammatory events in live mice. In addition, the Department´s faculty includes cardiovascular clinicians, thus providing an excellent environment to tackle these questions.
Candidates should possess:
• PhD in any field of Biomedical Sciences
• A strong publication record in international journals.
• Training and experience in cellular and molecular biology techniques and in vivo mouse models.
• Experience in the field of atherosclerosis and/or intravital imaging will be valued positively.
• A fluent command of spoken and written English.
The CNIC offers:
• Incorporation into a newly created and growing Research Center of international scientific relevance, within the public sector and managed by a Foundation.
• Integration into a young team, in an excellent scientific environment.
• Access to a modern infrastructure and advanced technologies, including state-of-the-art imaging facilities.
• Significant possibilities for personal development.
• A competitive salary, commensurate with experience and qualifications.
• Immediate incorporation.
Interested candidates should send a full CV, research interests and names and addresses of at least three referees by email, indicating the job reference in the subject field, to eisoininen@cnic.es
For more information, please consult our website: http://www.cnic.es
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Información complementaria de la oferta:
Imaging the Cardiovascular Inflammation and the Immune Response
Team leader: Andrés Hidalgo, PhD
Our laboratory is interested in various aspects of the inflammatory response. We
are developing techniques to visualize the molecular and cellular phenomena
that take place within the inflamed vasculature by utilizing multichannel
fluorescence intravital microscopy.
Imaging inflammation
During inflammation, leukocytes and platelets are recruited to activated or injured
vessels via adhesion receptors, chemokines and cytokines. Accumulating
leukocytes attach to the endothelium and crawl in search of areas to
extravasate. During this process they undergo redistribution of receptors on their
surface (polarization) to form discrete domains, each of which can mediate the
capture of circulating platelets and erythrocytes. As a result of these interactions
there is an exaggerated activation of the leukocyte which in turn releases toxic
mediators that damage the surrounding endothelium. This vascular damage can
translate into organ damage (e.g., lung or liver) and even death.
Transient or chronic increases in neutrophils levels in blood, and activation of
platelets, have been closely linked to the onset of acute cardiovascular events.
How the recently inflammatory phenomena described above may relate to the
onset and progression of the atherosclerotic plaque or other chronic
inflammatory injuries remains unexplored.
We will use several genetic murine models of atherosclerosis as well as novel
imaging modalities to uncover the events taking place at the arterial wall interface
in vivo during plaque progression. The tools to be implemented will also allow
investigating the immune and trafficking events at the microvasculature
surrounding the arterial wall (vasa vasorum and plaque neovessels).
For more info, please check:
http://www.cnic.es/investigacion/departamentos/dep1aterotrom/laboratorios/imag
eninfla/index.html?__locale=en
Selected publications
1. Imaging receptor microdomains on leukocyte subsets in live mice. EY Chiang, A
Hidalgo, J Chang, and PS Frenette. Nature Methods 4 (3): 219-222 (2007).
2. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic
interplay and distinct functions of PSGL-1, ESL-1 and CD44. A. Hidalgo, AJ Peired,
MK Wild, D. Vestweber and PS Frenette. Immunity 26: 477-489 (2007).
3. Heterotypic interactions enabled by polarized neutrophil microdomains mediate
thrombo-inflammatory injury. A. Hidalgo, Jungshan Chang, Jung-Eun Jang, Anna J.
Peired, Elaine Y. Chiang and Paul S. Frenette. Nature Medicine 15(4): 384-391
(2009b)
Laboratory of Molecular and Genetic Cardiovascular Pathophysiology
Team Leader: Vicente Andrés, PhD
1. Description of the Laboratory, interest, research projects, etc
Atherosclerosis is a chronic inflammatory process triggered by several risk factors, which, acting
alone or in combination, promote endothelial damage and the accumulation within the artery wall
of various cell types, including vascular smooth muscle cells (VSMCs) and circulating leukocytes
(monocytes, T-cells and dendritic cells), and non-cellular material, such as modified lipids and
extracellular matrix components. Circulating leukocytes adhere to the injured endothelium and
migrate towards the subendothelial space. Neointimal monocytes differentiate into macrophages
which avidly internalize modified LDLs and give raise to the highly proliferative lipid-laden foam
cells that characterize early fatty streaks. Activated neointimal macrophages and lymphocytes
produce a plethora of inflammatory mediators that induce the proliferation of VSMCs and their
migration towards the growing atherosclerotic lesion. At advanced disease states, rupture or
erosion of vulnerable plaques can promote thrombus formation and acute ischemic events (e.g.
acute myocardial infarction -AMI, stroke). Abnormal VSMC hyperplasia is also a feature of
restenosis, the major limitation to the long-term success of revascularization via stent
deployment. Remarkably, the recent introduction of drug-eluting stents which deliver cytostatic
agents at the site of intervention has revolutionized interventional cardiology, as these devices
decrease the rate of restenosis by up to 80% compared to bare metal stents.
Specific Objectives:
1. To unravel novel molecular mechanisms involved in neointimal lesion development in
the context of native atherosclerosis and restenosis. In addition to our traditional
approach using mice harboring whole-body genetic alterations, we will utilize Cre/lox
strategies to achieve gene ablation specifically in cell types involved in neointimal
thickening, including VSMCs, endothelial cells (ECs) and macrophages.
2. To investigate the association between SNPs in cell cycle regulatory genes and human
susceptibility to develop in-stent restenosis, and to investigate the functional
consequences of such genetic variants.
3. To investigate the role of the nuclear envelope in the regulation of signal transduction,
gene expression and cell cycle activity in pathophysiological processes, including aging
and cardiovascular disease (CVD).
The results of these investigations should not only improve our basic knowledge of the molecular
and cellular mechanisms and genetic factors that govern atheroma development in different
pathological scenarios, but may also identify potential therapeutic targets amenable for
pharmacological interventions and provide the rational for the development of novel diagnostic
tools for the early detection of individuals at high risk of CVD, a topic of great interest given that
only ~50% of AMI patients present with traditional risk factors (e.g., hyperlipidemia, smoking,
hypertension, obesity, etc).
Selected publications
Original articles
Chen, D., Krasinski, K., Chen, D., Sylvester, A., Chen, J., Nisen, P. D. and Andrés, V. 1997.
Downregulation of cyclin-dependent kinase 2 activity and cyclin A promoter activity in
vascular smooth muscle cells by p27KIP1, an inhibitor of neointima formation in the rat carotid
artery. J. Clin. Invest. 99: 2334-2341.
Chen, D., Asahara, T., Krasinski, K, Witzenbichler, B, Yang, J. Magner, M, Kearney, M. Frazier,
W. A., Isner, J. M. and Andrés, V. 1999. Antibody blockade of thrombospondin-1 accelerates
reendothelialization and reduces neointima formation in balloon-injured rat carotid artery.
Circulation 100: 849-854.
Castro, C., Díez-Juan, A., Cortés, M. J. and Andrés, V. 2003. Distinct regulation of mitogenactivated
protein kinases and p27Kip1 in smooth muscle cells from different vascular beds: A
potential role in establishing regional phenotypic variance. J. Biol. Chem. 278: 4482-4490.
Díez-Juan, A. and Andrés, V. 2003. Coordinate control of proliferation and migration by the
p27Kip1/cyclin-dependent kinase/retinoblastoma pathway in vascular smooth muscle cells and
fibroblasts. Circ. Res. 92: 402-410.
Díez-Juan, A., Pérez, P., Aracil, M., Sancho, D., Bernad, A., Sánchez-Madrid, F. and Andrés, V.
2004. Selective inactivation of p27Kip1 in hematopoietic progenitor cells increases neointimal
macrophage proliferation and accelerates atherosclerosis. Blood 103:158-161.
Poch, E., Carbonell, P., Franco, S., Díez-Juan, A., Blasco, M. A. and Andrés, V. 2004. Short
telomeres protect from diet-induced atherosclerosis in apolipoprotein E-null mice. FASEB J.
18:418-420.
Ivorra, C., Kubicek, M., González, J. M., Sanz-González, S. M., Álvarez-Barrientos, A.,
O'Connor, J. E., Burke, B. and Andrés, V. 2006. A mechanism of AP-1 suppression through
interaction of c-Fos with lamin A/C. Genes Dev. 20:307-320.
González, J.M., Navarro-Puche, A., Casar, B., Crespo, P. and Andrés, V. 2008. Fast regulation of
AP-1 activity through interaction of lamin A/C, ERK1/2 and c-Fos at the nuclear envelope. J.
Cell. Biol. 183: 653-666.
González-Navarro, H., Vinué, A., Vila-Caballer, M., Fortuño, A., Beloqui, O., Zalba, G., Burks, D.,
Díez, J. and Andrés, V. 2008. Molecular mechanisms of atherosclerosis in metabolic
syndrome: Role of reduced IRS2-dependent signaling. Arterioscl. Thromb. Vasc. Biol.
28:2187-2194.
González-Navarro, H., Naim Abu Nabah, Y., Vinué, A., Andrés-Manzano, M.J., Collado, M.,
Serrano, M. and Andrés, V. p19Arf deficiency reduces macrophage and vascular smooth
muscle cell apoptosis and aggravates atherosclerosis. J. Am. Coll. Cardiol. (In Press).
Reviews
Fuster, J. J. and Andrés, V. 2006. Telomere biology and cardiovascular disease. Circ. Res.
99:1167-1180
Andrés, V. and González, J.M. 2009. Role of A-type lamins in signaling, transcription and
chromatin organization. J. Cell Biol. 187 (En prensa).
Fuster, J.J., Fernández, P., González-Navarro, H., Silvestre, C., Naim Abu Nabah, Y. and
Andrés, V. Control of cell proliferation in atherosclerosis: Insights from animal models and
human studies. Cardiovasc. Res. En prensa.
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