KirPhagy project aims to characterize the role of autophagy in the biology of natural killer (NK) cells and identify the implications of NK-autophagy axis in haematological malignancies. As the main function of NK cells is to discriminate with the help of their KIR receptors (Killer Immunoglobulin-like Receptors) between normal and malignant cells based on the cell membrane expression of MHC I (major histocompatibility complex class I) molecules, blood cancer targeted therapeutic strategies to improve the in vivo KIR-dependent NK efficiency of this recognition process are paramount to be developed.
Autophagy (literally “self-eating”) is an evolutionarily intracellular degradative pathway that is preeminent to the cellular and organismal homeostasis. Since autophagy is also involved in the degradation of cellular receptors, the novel approach we are introducing, of manipulating the surface expression of KIR on NK cells via autophagy, would be key in defining strategies for amplifying the process of recognition and killing of malignant cells by NK.
We are proposing to develop a project that requires multidisciplinary expertise at the interface between bioinformatics, bench/hands-on research work and clinical input. More specific, we shall initially identify by bioinformatics analysis the KIR receptors potentially acting as autophagy substrates, followed by in vitro validation of these data (KIR genotyping and flow-cytometry phenotyping) using peripheral NK cells isolated from healthy controls and patients with blood cancers.
The project and its director have several strong points like profound knowledge of autophagy and immunology, access to a world class infrastructure and international network developed during her PhD at the University of Cambridge, United Kingdom.
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