Saula Checquolo

La Dott.ssa Saula Checquolo si è laureata con Lode in Scienze Biologiche presso l’Università “La Sapienza” di Roma nel 2000 ed ha conseguito nello stesso Ateneo il titolo di Dottore di Ricerca in Scienze Immunologiche nel 2004. E’ stata borsista AIRC dal 2005 al 2006 e borsista FIRC dal 2006 al 2008. Dal 2008 al 2022 è stata ricercatore del Settore Scientifico-Disciplinare MED-04 (Patologia Generale) presso la I Facoltà di Medicina e Chirurgia – Polo Pontino – dell’Università degli Studi di Roma “La Sapienza”. Attualmente è risultata vincitrice della procedura di valutazione a Professore di seconda fascia – SSD MED/04 ed è in attesa della presa di servizio presso la stessa Facoltà.

“Il progetto di ricerca di cui sono responsabile si propone di investigare nel dettaglio i meccanismi molecolari responsabili dello sviluppo e progressione del cancro dell’ovaio, con particolare riferimento alla valutazione meccanicistica e funzionale dell’asse Pin1-Notch3 rispetto alla risposta ai trattamenti convenzionali con farmaci chemioterapici. Si tratta di una ricerca di base condotta sia attraverso studi in vitro che in vivo, in modelli preclinici murini, coniugata quindi con importanti aspetti traslazionali, finalizzati all’implementazione dei percorsi terapeutici di pazienti che sviluppano forme di tumore spesso resistenti ai trattamenti e/o recidivanti in forma più aggressiva e metastatizzante. In questo senso, il progetto assume una valenza importante nell’ambito degli obiettivi dell’Istituto Pasteur.”

Molecular dissection of Notch3-Pin1 cross-talk: novel approaches of targeted therapy in ovarian cancer

Ovarian cancer (OC) is highly metastatic, rendering the current treatments ineffective. As a result, elucidating which pathways are involved in OC progression becomes a paramount issue in order to develop appropriate approaches directed against those effectors.

Notch signaling is frequently activated in OC and contributes to the proliferation and survival of cultured OC cells as well as to tumor formation and angiogenesis in xenograft models. In particular, Notch3 activation renders OC cells more resistant to carboplatin and it is frequently associated with OC progression, tumor invasion and metastasis, which are of high relevance as most OC-bearing patients experience disease recurrence. In this scenario, the Epithelial-mesenchymal transition (EMT) process needs to be considered, as the acquisition of the EMT phenotype is associated with drug resistance, and Notch3 significantly interferes with the EMT regulation and the metastatic capacity of malignant cells. This suggests that Notch3 can represent both a prognostic marker and a therapeutic target for the treatment of OC patients. However, the underlying molecular mechanisms of Notch3 activity are not yet very clear. Recently, we have shown that the peptidyl-prolyl isomerase Pin1 positively regulates Notch3 protein expression and function in T-cell acute lymphoblastic leukemia (T-ALL), thus influencing the Notch3-dependent aggressiveness properties of T-ALLs. Based on our preliminary results, we hypothesize to reveal, analyze and fully understand the same functional Notch3/Pin1 cross-talk also in OC context. In particular, we will focus on functional studies that will include Mass Spectrometry (MS) analysis, in vitro and in vivo studies by using both OC cells and human primary tumors, patients-derived, in the presence or absence of Pin1 (i.e. pharmacological inhibition by All-Trans Retinoic Acid, ATRA, or RNA interference), in order to evaluate the functional significance of the Pin1 inhibition on Notch3-dependent EMT regulation.

Our preliminary data showed the Notch3/Pin1gene correlation in a cohort of OC-bearing patients, significantly related with an advanced tumor stage, thus suggesting that Notch3/Pin1 axis might be involved in the acquisition of aggressive phenotype also in OC context. Therefore, we expect to identify therapeutic options based on Pin1 inhibition aimed at targeting Notch3, and finally restoring OC chemo-sensitivity and inhibiting metastatic spread