IBBE > NEWS ED EVENTI > Progetti > Progetto di Ricerca di Rilevante Interesse Nazionale (PRIN)- PNRR dal titolo “Plasma membrane amino acid transporters and VDACs in the metabolic rewiring of glioblastoma: from multi-omic approaches to targeted treatment”

Progetto di Ricerca di Rilevante Interesse Nazionale (PRIN)- PNRR dal titolo “Plasma membrane amino acid transporters and VDACs in the metabolic rewiring of glioblastoma: from multi-omic approaches to targeted treatment”

Cancer cells, to support their high proliferative rate, undergo a metabolic rewiring known as the Warburg effect that improves glycolysis and the oxidation of glutamine at both cytosolic and mitochondrial levels. This phenomenon mainly arises from the deregulated expression of specific genes, including glutamine and essential amino acid transporters located in the plasma membrane, namely the SLC family members ASCT2, xCT, SNATs, LAT1 and ATB0,+, and porins (or VDACs) located in the outer membrane of mitochondria that allow the passive diffusion of ions and small metabolites in and out of the organelle. It is, indeed, not a coincidence that the above-mentioned genes are over-expressed in virtually all human cancers and correlate with a peculiar degree of malignancy and prognosis. GlioBlastoma Multiforme (GBM) is a common brain cancer form characterized by a poor prognosis and being resistant to radio and chemotherapies currently available. In GBM, different combinations of genetic alterations correlate with amino acid-related metabolism and, hence, cell proliferation and survival rates. These features trigger different degrees of malignancy ranging from I to IV grade. Nevertheless, the precise role of amino acid and metabolite transporters and, in general, the molecular mechanisms behind the deregulation of GBM metabolism have been poorly investigated. Based on the above, with this project, we propose to expand our knowledge in this field by investigating in detail the network of SLC and VDAC transporters by using a multi-omic approach. In particular, a panel of relevant GBM cellular models, mimicking the four degrees of malignancy, will be screened for a comprehensive analysis of transcriptomic, metabolomic and respiratory profiles. Starting from the obtained data, the proposed project aims to identify: i) the key players (transporters, porin, lncRNAs and/or transcription factors) driving the metabolic rewiring of GBM cells, and ii) any putative chemical compounds targeted to involved transporters to be screened as potential chemotherapeutics. Overall, the proposed project aims to achieve an unprecedented level of understanding of factors and pathways driving GBM metabolism. At the same time, the project offers the added benefit of potentially highlighting novel prognostic biomarkers and therapeutic drug(s) for the treatment of glioblastoma.

Codice identificativo P2022RLLBB – CUP B53D23033170001, approvato a valere del Bando PRIN 2022 PNRR Decreto Direttoriale n. 1409 del 14 settembre 2022, – Decreto Direttoriale di ammissione a finanziamento prot. n. 1364 del 01/09/2023.

ENTE FINANZIATORE: Ministero dell’Istruzione, dell’Università e della Ricerca (MUR)

ANNO INIZIO: 2023
ANNO FINE: 2025

RESPONSABILE SCIENTIFICO: Dott. Flaviana Marzano

Indirizzo

Via Giovanni Amendola, 122/O
70126 Bari (BA) Italia

Share
IBIOM - Institute of Biomembranes, Bioenergetics and Molecular Biotechnology of Bari Managed by elabora next