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Laboratory/department/unit description where is going to be performed the scientific work

Immunobiology of inflammation lab

Our main interest is how dendritic cells (DC) and macrophages modulate immunity and inflammation. We are interested in the analysis of DC subsets, their specific functions and plasticity. We have found that Batf3-dependent DCs are crucial for generation of Th1 immunity through the production of IL-12 (Martínez-López et al. 2015. Eur. J. Immunol.). We analyzed the Th1-immunity model of infection by the eukaryote parasite Leishmania major, which induces tissue damage and it is also a eukaryote that mimics many danger signals from tissue. We have also found that Batf3-dependent DCs do not play a major role in the development of atherosclerosis. In contrast, in collaboration with the group of Dr. Ignacio Melero (CIMA and Clínica Universitaria de Navarra, Pamplona) we have found that cross-presenting DCs are crucial for the generation of a basal immune response that can be rescued by immunostimulatory antibodies for cancer immunotherapy (Sánchez-Paulete et al. 2015, Cancer Discovery).

We have also analyzed the modulation of signals through C-type lectin receptors and have found that SHIP-1 associates to the intracellular hemITAM motif in Dectin-1 and selectively modulates its ability to induce reactive oxygen species in DC (Blanco-Menéndez et al. 2015. J. Immunol.). In addition, we are working on DNGR-1 as a model C-type lectin that detects tissue damage during infection and we have determined an impact in the CD8+ T cell memory response. We are also analyzing the effects of sensing non-self and damaged-self in the metabolism of myeloid cells. We believe that this research has potential for the development of new vaccines and immunotherapy strategies.

Staff enrolled in the project

    DAVID SANCHOAssistant Professor

    914531200 ext 2010

    David identified CLEC9A/DNGR-1 as a specific marker of cross-presenting dendritic cells in the mouse and the human. He demonstrated that in vivo targeting to DNGR-1 generates effective anti-tumor immunity. His current lab at CNIC studies the role of the cross-priming and dendritic cell subsets in physiopathological models and its possible use to obtain new strategies of immunotheraphy.

  • Stefanie K. Wculek
    Stefanie K. WculekPostdoctoral researcher

    914531200 ext 3316

    Stefanie was involved in elucidating a pro-tumourigenic role of the innate leukocytes neutrophils in mouse models of breast cancer metastasis to the lung. They found neutrophil-derived leukotrienes to directly support cancer stem cell-like cells and show that pharmacological inhibition of leukotrienes limits metastasis.

  • Michel Enamorado
    Michel EnamoradoPhD student

    914531200 ext 2305

    Michel was studying the role of cytokines in cancer immunotherapies. He contributed to the characterization of a human IL-2 mutant with a higher antitumor efficacy and lower toxicity than the wild type. Now he is interested in the metabolism of dendritic cells and the function of cross-presenting dendritic cells in cancer.

  • Dr. Salvador Iborra
    Dr. Salvador IborraPostdoctoral researcher

    914531200 ext 2304

    Salvador Iborra defined the role of the different Ras GTPases proto-oncogenes in T helper cell differentiation. He also found that the generation of functional long-lived protective memory CD8+ T lymphocytes requires N-ras. Currently, he studies the role of dendritic cell subsets and cross-presentation in response to infection and vaccination.