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Tag: p38α (Page 2 of 2)

CICERONE program 2017 for Masters and advanced undergraduate students

Though the CICERONE Program is open to Masters and advanced undergraduate students for extending their scientific training through hands-on experience of laboratory-based biomedical research during the summer recess. In addition to carrying out a supervised research project, the students also attend CNIC seminars.

The aim of the program is to give university students first-hand knowledge of biomedical research so that they can make more informed choices about the possibility of pursuing a scientific career.

Link Size
2017 Guidelines 386 KB
Application form
Document of acceptance 545 KB

For the 2017 call, we are offering two different research projects:

  • Role of p38MAPK in metabolic diseases: Metabolic syndrome is a medical disorder defined by the co-occurrence of obesity, impaired glucose tolerance, dyslipidemia and hypertension. Stress activated protein kinases have been shown to control both obesity by itself and diabetes associated to obesity. These stress kinases are activated by several MAPK activated kinases (MKK). We want to investigate the role of MKK3 in this process and the molecular mechanism by which this kinase could affect diabetes.
  • p38MAPK in heart phisiology: The p38 MAPK pathway transduces a variety of extracellular signals regulating cellular responses to stress, being implicated in cell proliferation, differentiation and apoptosis. Its implication in the development of human diseases it is being deeply studied. Four p38 MAPK family members have been identified: p38α, β, γ and δ.
    Preliminary data from our laboratory show that these kinases may control cytokine production during acute and chronic inflammatory processes. Moreover, studies with genetically modified mice made in our laboratory confirm that p38MAPKs have a role in the development of the heart. Our main objective is to determine if the regulation of the p38MAPK signaling pathway could have beneficial effects in the cardiac response to exercise.

Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP-1 and p38

Amelia Escolano, Sara Martínez‐Martínez, Arántzazu Alfranca, Katia Urso, Helena M Izquierdo, Mario Delgado, Francisco Martín, Guadalupe Sabio, David Sancho, Pablo Gómez‐del Arco & Juan Miguel Redondo.

Macrophages contribute to tissue homeostasis and influence inflammatory responses by modulating their phenotype in response to the local environment. Understanding the molecular mechanisms governing this plasticity would open new avenues for the treatment for inflammatory disorders.

p38 phosphorylation in  macrophages.

p38 phosphorylation in macrophages.

We show that deletion of calcineurin (CN) or its inhibition with LxVP peptide in macrophages induces an anti-inflammatory population that confers resistance to arthritis and contact hypersensitivity. Transfer of CN-targeted macrophages or direct injection of LxVP-encoding lentivirus has anti-inflammatory effects in these models. Specific CN targeting in macrophages induces p38 MAPK activity by downregulating MKP-1 expression. However, pharmacological CN inhibition with cyclosporin A (CsA) or FK506 did not reproduce these effects and failed to induce p38 activity. The CN-inhibitory peptide VIVIT also failed to reproduce the effects of LxVP. p38 inhibition prevented the anti-inflammatory phenotype of CN-targeted macrophages, and mice with defective p38-activation were resistant to the anti-inflammatory effect of LxVP.

Our results identify a key role for CN and p38 in the modulation of macrophage phenotype and suggest an alternative treatment for inflammation based on redirecting macrophages toward an anti-inflammatory status.

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