Research Theme: Molecular Neuro-Oncology  

Keywords: Glioblastoma, kinase inhibitor, angiogenesis

The research focus of our lab is the brain tumor glioblastoma (GBM). Our research has evolved over time, but the characterizing red trail has always been GBM. We studied different aspects, some dealing with GBM tumor biology, others are therapy-oriented. GBM is the most aggressive brain tumor in the adults, and, despite all the efforts spent by the scientific community, its prognosis remains poor, with a median survival at diagnosis of about 14 months. The main histological features of GBM tumors are massive necrosis and prominent angiogenesis. Angiogenesis represents a distinctive peculiarity of GBM, and a landmark for diagnosis. Anti-angiogenic treatments targeting tumor vasculature are considered the new frontier in GBM therapy but, unfortunately, they are substantially disappointing the expectations. Our most recent work focused on two multikinase inhibitors, small molecules targeting key signaling pathways in GBM growth and angiogenesis: 
– regorafenib, a molecule recently introduced in the clinical management of relapsed GBM. We are carrying on a study for unravelling the molecular mechanisms of GBM response to regorafenib. The study is based on a chemogenomic CRISPR/Cas9 screening.
– axitinib, a small molecule which targets the receptors of Vascular Endothelial Growth Factor with high specificity. The study is based on preclinical models (brain tumor xenografts) to verify in vivo our in vitro data about the possibility of using antioxidants to reduce axitinib toxicity with no impairment of the anti-cancer activity.
Further, we are participating in an ongoing study on the possibility of using functionalized liposomes as specific delivery vehicles to central nervous system for gene therapy for the neurodegenerative disease Spinal Muscular Atrophy (SMA).

Education:

• 1998- PhD in Endocrinology and Metabolism (University of L’Aquila)
• 1994-Qualification to the profession of biologist (La Sapienza University of Rome)
• 1992- Degree in Biology, summa cum laude (La Sapienza University of Rome)

Positions:

• 2018: ASN-MIUR- National Academic Qualification as Associate Professor in Applied Biology (05/F1)
• 2009-present: Staff scientist (Primo Ricercatore), CNR
• 2003-2008: Fixed-term researcher, CNR
• 2003-2004: Adjunct professor of Neurobiology (Università Cattolica del Sacro Cuore)
• 2003: Telethon Research fellow
• 1999-2002: Postdoc fellow (Assegnista di Ricerca) (CNR-INMM)

1) Falchetti ML et al (2003). Glioblastoma induces vascular endothelial cells to express telomerase in vitro. Cancer Res 63(13):3750-4. PMID: 12839970
2) Pallini R et al (2006). Telomerase inhibition by stable RNA interference impairs tumor growth and angiogenesis in glioblastoma xenografts. Int J Cancer doi: 10.1002/ijc.21613
3) Pacioni S et al (2017). Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts. Stem Cell Res Ther (doi: 10.1186/s13287-017-0516-3).
4) Mongiardi MP et al (2019.) Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation. Oncogene (doi: 10.1038/s41388-019-0798-2.)
5) Pacioni S et al (2019). Brain invasion along perivascular spaces by glioma cells: relationship with blood-brain barrier. Cancers (doi: 10.3390/cancers12010018)
6) Mongiardi MP et al (2021). Cancer response to therapy-induced senescence: a matter of dose and timing. Cancers (doi: 10.3390/cancers13030484).
7) Simonis B et al (2022). Transport of cationic liposomes in a human blood brain barrier model: Role of the stereochemistry of the gemini amphiphile on liposome biological features. J Colloid Interface Sci  (doi: 10.1016/j.jcis.2022.07.025).

Go to the publications page 

I’m currently involved in:

• Study Group on Brain Tumors (http://www.tumori-cerebrali.it/), a network of scientists and clinicians devoted to the study of brain tumors.
• NEURONET Consortium, a network to investigate the molecular mechanisms of neuro-pathologies. I am one of the referents for the area of neuro-oncology.

Grants

FESR Fondo Europeo di Sviluppo Regionale – Programma Operativo  regionale del Lazio – Programmazione 2014-2020. Avviso Pubblico: “Progetti di Gruppi di ricerca 2020”. Titolo del progetto: “LIMONE: Nanoparticelle lipidiche per raggiungere il motoneurone”.++

FESR Fondo Europeo di Sviluppo Regionale – Programma Operativo  regionale del Lazio – Programmazione 2014-2020. Avviso Pubblico: “Progetti di Gruppi di ricerca 2020”. Titolo del progetto: “Strategie per implementare la terapia del glioblastoma”.

Italian Ministry of Health-Ricerca Finalizzata bando 2019. Titolo del progetto: “Control of growth and invasiveness of glioblastoma by modulation of ciliogenesis in glioma stem cells. A novel target against glioblastoma for precision medicine”.

AIRC IG 2021. Titolo del progetto: “Regorafenib in glioblastoma: molecular characterization of tumor response and translational opportunities”.