MSCA Postdoctoral Fellowship Innate immunity and cancer

Position: MSCA Postdoctoral Fellowship on Innate immunity and cancer
Section of General Pathology at the University of Verona

Organisation / Company Università degli Studi di Verona Department Department of Medicine Laboratory Section of General Pathology at the University of Verona Is the Hosting related to staff position within a Research Infrastructure? No

Prof.

Marco

A.Cassatella invitesscholarstopresentexpressionsofinterestinapplyingjointlywith the  Department of Medicine  -  Section of General Pathology at the University of Verona for a Marie Skłodowska‑Curie Postdoctoral Fellowships (MSCA‑PF) on  Innate immunity and cancer.

The lab offers several ongoing projects:
1) Identification and molecular characterization of very immatureCD
34+/-neutrophilandmonocyteprogenitorsinhealthy humandonorsandcancerpatients;
2) to shed definitive light on the phenotypic, transcriptomic, and functional features of human monocytic myeloid-derived suppressor cells (M-MDSCs) by investigating CD14+HLA- DRlow/⁻CXCR1- and CD14⁺HLA-DRlow/⁻CXCR1+ monocyte subtypes in different types of cancer patients and G-CSF-treated donors (GDs). In addition, since an emerging question is whether M-MDSCs consist of normal mature monocytes that have acquired suppressive capacities or whether they represent cells that are reprogrammed during monocyte differentiation, we intend to investigate the ontogenesis of human M-MDSCs once the definitive CD14+HLA-DRlow/⁻CXCR1- and CD14⁺HLA-DRlow/⁻CXCR1+ phenotype of M-MDSCs is clarified;
3) Molecular characterization of the fate of slan+monocytes in human tumors and definition of which macrophage/dendritic cell populations they give origin to by bioinformatic approaches;
4) molecular bases of human neutrophil activation. These projects require expertise in cell and molecular biology/biochemistry methodologies, such as cell isolation and culture, flow cytometry and sorting, RNA isolation for bulk RNAseq and scRNAseq, ATAC-seq, and so forth. All these techniques are ongoing in the lab and thus can be learned locally. Recent papers focused on these projects have been published in Nature Immunology, Cellular and Molecular Immunology, Cell Reports Medicine, Cancer Immunology Research, Cell Reports, and Frontiers in Immunology.

Hosting research group / Supervisor
Cassatella’sscientificcareerhasalwaysfocusedonstudiesaimedatunderstanding,at the molecular level,themechanismsregulatingtheeffectorfunctionsofinnateimmunesystemcellsinthefieldof innate immunity and cancer. Since established in Verona, Cassatella’s group has contributed by uncovering the notion that polymorphonuclear neutrophils are not only targets of cytokines/factors that modulate their effector/antitumor functions, but may also represent important sources of many immunoregulatory molecules, including cytokines themselves Prof. Cassatella has also made significant, if not the initial, contribution uncovering that human neutrophils represent key cellular playersinregulatingangiogenesis,eitherpositively,particularlyviathereleaseof

VEGFornegatively,particularlyviathegenerationofmassiveamountsofangiostatin. Furthercontributionsgivenbythe Cassatellainoncologyrelate to his pivotal studies on the molecular mechanisms activating CD16/Fc g RIIIA in human Natural Killer (NK) cells, as well as on the molecular mechanisms regulating the production of reactive oxygen intermediates by myeloid cells, which are important mediators for cancer cytotoxicity operated by myeloid cells. Recently, Casatella’s group has dedicated great research effort in characterizing the role of human slan+monocytes in tumors reportingtheirspecificandselectiveinvolvementinthenodalimmuneresponsestowardscarcinoma cells,andtheirabilitytoperform

ADCC(atlevelssimilartothoseexertedby

NKcells)
Finally, Cassatella’sgrouphasrecentlyreportedtheidentificationofnovelCD
34+andCD
34dim/-progenitors (NCPs) of human neutrophils , which now requires an extensive characterization, as well as the definition of their potential role in tumors. Selected candidates will be offered both academic and administrative support from the Centre / Department and the University of Verona Grant Office with regard to the proposal preparation.

Selected candidates will be offered both…