Prof.ssa Maria Letizia Trincavelli
PhD project Title:
System Biology: studying molecular pathways
Glioblastoma multiforme (GBM) is an aggressive and invasive brain tumour, with a high mortality rate. The therapeutic treatment usually consists of surgical resection, followed by radiotherapy and the administration of the alkylating agent Temozolomide. Significant intra- and inter-tumour heterogeneity has been associated to aberrations in different intracellular pathways and a peculiar tumour microenvironment (TME) that contributes greatly to GBM progression. Among the different intracellular pathways, the deregulation of the oncosuppressor protein p53 and the reactivation of its endogenous function represents an important tool in GBM treatment. The p53 function might be impaired by multiple mechanisms such as the overexpression of its primary cellular inhibitor, the Murine Double Minute 2 protein (MDM2) promoting tumour proliferation. TME consists of diverse stromal cell types such as endothelial cells, astrocytes, microglia, glioblastoma associated macrophages (GAMs), glioblastoma associated fibroblast (TAFs), mesenchymal stem cells (MSCs), and extracellular factors. Adenosine (ADO) is one of the several extracellular factors in the TME. Under physiological conditions, extracellular adenosine levels remain in nanomolar range and increase up to 100 times during inflammation, hypoxia, or tumour formation. The role of extracellular ADO in GBM is still unclear. Some literature data reported that ADO plays a prominent role in GBM pathogenesis, growth, angiogenesis and invasiveness. The aim of my PhD project will be to investigate the intracellular molecular pathways involved in the pathogenesis of GBM and the impact of TME on its aggressive traits.
Oral communications at congress:
Pietrobono D, Giacomelli C, De Leo M, Daniele S, Bertoli A, Braca A, Trincavelli ML, Martini C. Human glioblastoma cell apoptosis is induced by Rosemary officinalis through the p53 functional reactivation. “Bio-energetics, Metabolism and Nutrition: from molecules to systems. Bio-energetica, Metabolismo e Nutrizione: dalle molecole ai sistemi – Meeting annuale dei Gruppi Membrane, Nutrizione e Biologia computazionale e dei sistemi della SIB. Bologna 2018, 25-26 June.
Pietrobono D, Trincavelli ML. Modulazione di vie di segnale coinvolte nei processi di apoptosi e invasività del glioblastoma. Di nuovo TUM: mappatura interregionale delle tematiche SIB tra Toscana, Umbria e Marche, 2019, June 11, Ancona, Italy
Poster communications at congress:
Pietrobono D, Piccarducci R, Giampietri L, Daniele S, Baldacci F, Nicoletti V, Frosini D, Petrozzi L, Trincavelli ML, Tognoni G, Bonuccelli U, Martini C. α-synuclein and its heterocomplexes significantly decrease in erythrocytes of Alzheimer’s Disease patients. International conference, II edition, “More than neurons: toward a less neuronocentric view of brain disorders”, Torino Incontra, Nov 29th-Dec 1st, 2018- Turin, Italy
Pietrobono D, Giacomelli C, Martini C, Trincavelli ML. Adenosine promotes glioblastoma aggressiveness modulating the epithelial-mesenchymal transition. 31a Riunione nazionale “A. Castellani” dei dottorandi di ricerca in discipline biochimiche 2019, June 3-7, Brallo di Pregola, Italy.
Pietrobono D, Daniele S, Parravicini C, Eberini I, Martini C, Trincavelli ML. Physical and functional interaction between GPR17 and the chemokine receptor 2: a promising tool for managing remyelination. First European Purine Meeting, 2019, 4-6 September, Santiago de Compostela, Spain.