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AUB

American University of Beirut
17 Projects, page 1 of 4
  • Funder: EC Project Code: 268729
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  • Funder: EC Project Code: 785917
    Overall Budget: 2,500,000 EURFunder Contribution: 2,500,000 EUR

    In acute promyelocytic leukaemia (APL), retinoic acid (RA) and Arsenic trioxide (As) bind PML/RARA and promote its degradation. Exploring the mechanistic bases for APL response to the RA/As combination, we found that upon PML/RARA degradation the normal PML allele activates a PML/P53 checkpoint absolutely required for APL cure in mice or patients. Physiologically, PML behaves as an oxidative stress sensor and contributes to redox homeostasis. PML organizes nuclear bodies (NBs), domains that recruit multiple client proteins and may facilitate their post-translational modifications (PTM), particularly conjugation of SUMOs. This somehow controls multiple downstream pathways such as P53, but also RB, HIF1A or interferon (IFN). In APL, NB-disruption blunts P53-driven senescence, contributing to oncogenesis and therapy resistance. Critically, PML expression and/or NB-formation are lost upon many viral infections or during cancer development. The mechanism(s) underlying the selective pressure to loose PML expression in multiple cancers remains incompletely understood. Our aim is to mechanistically dissect PML signalling in vivo and therapeutically restore it in malignancies where it is inactivated. We first propose a broad exploration of PML in mice to identify basal and stress-induced PML PTM and identify the repertoire of proteins sumoylated in a PML- dependent manner. We will generate a series of PML knock-in mutant mice and analyse their P53- regulated redox homeostasis. We will mechanistically explore PML/P53-driven senescence in three leukaemia models where we have evidence for basal or therapy-responsive NB-modulation: acute myeloid leukaemia expressing NPMc and IFN-sensitive Tax- or JAK2-driven leukaemias. We will screen chemical libraries for drugs modulating PML expression and/or NB biogenesis. Finally, we will integrate our findings to elaborate innovative therapeutic strategies based on restoration of the PML/P53 checkpoint in leukaemia with unmet medical needs

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  • Funder: EC Project Code: 230658
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  • Funder: EC Project Code: 244717
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  • Funder: EC Project Code: 872260
    Overall Budget: 2,476,480 EURFunder Contribution: 2,476,480 EUR

    TARGETED-MPI aims to address gender inequality in Business and Management (B&M) schools through the development and effective implementation of Gender Equality Plans (GEPs). The complex and multidisciplinary nature of B&M schools constitutes an important research site to examine gender equality. The TARGETED-MPI consortium includes research organisations operating in diverse academic cultures and socio-economic settings in Europe (Greece, Sweden, Belgium, UK) and Lebanon, which allows the development of rich GEPs and the understanding of the conditions of applicability and transferability of GEPs across Europe and Middle East and North Africa (MENA) countries. We will use an action-based research and transparent end-to-end stakeholder engagement strategy that is critical for the development and implementation of GEPs. The innovative cultural web tool will be used to identify overt and covert gender bias and barriers in partner organisations. A two-phase planning-implementation-monitoring-and-evaluation approach will be used to support the early deployment and assessment of GEPs and the provision of timely feedback for improving the initial GEPs. An independent expert will work closely with the project team to provide impartial ex-ante and ex-post evaluation of the GEPs. A Network of Gender Equality Observatories (GEOs) will be established in the B&M schools of the participating institutions to foster the sustainability of the GEPs and support the dissemination of the project results. The higher and middle management of all participating institutions have made unequivocal commitments for implementing the GEPs to achieve institutional change. TARGETED-MPI has also secured the support of critical gender equality stakeholders including professional organisations. The implementation of GEPs will improve GE in academic careers and gender participation in decision making bodies, and will foster the inclusion of gender consideration in research and innovation content.

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