angelica mancusi

PhD Graduate

PhD program:: XXXV


supervisor: saula checquolo
advisor: saula checquolo
co-supervisor: isabella screpanti

Thesis title: Molecular dissection of Notch3-Pin1 cross-talk to overcome Platinum resistance in Ovarian Cancer

Ovarian Cancer (OC) is one of the most lethal gynecological malignancies as acquired resistance to standard Platinum (PT)-based therapies frequently occurs. Notably, an increasing number of studies proved that Notch3 receptor is altered in a wide panel of OC and it confers Platinum resistance to OC cell lines. Therefore, effective targeting of Notch3 may restore Platinum sensitivity. A growing body of evidence sustains a pivotal role of Post-Translational Modifications (PTMs) in regulating protein function as they may influence protein activity and stability. Therefore, the exploitation of Notch receptors PTMs is emerging as a novel therapy approach, as it allows the identification of potential Notch interactors regulating its function. In this scenario, we previously demonstrated that the peptidyl- prolyl cis/trans isomerase Pin1 positively regulates Notch3 protein expression in T-cell acute lymphoblastic leukaemia (T-ALL), by binding specific phosphorylated residues. In the present study we wondered whether and how Pin1-Notch3 cross-talk might occur also in ovarian cancer context. Collectively, the main aims of the present project are: 1. to investigate the relevance of Pin1-N3 axis targeting in the response to Platinum therapies; 2. to dissect the key molecular oncogenic mechanisms involved in Pin1/Notch3 cross-talk by focusing our attention on the “less known” Notch3 PTMs potentially related to other Notch3-regulators activities. Therefore, investigate the potential relevance of Pin1/Notch3 cross-talk could allow the escape from this regulation process in the OC context. Targeting Pin1 can influence Notch-dependent OC behavior by maximizing the efficacy of platinum-based therapies in order to restore chemo- sensitivity and reduce tumor spread. The final goal of this project is the possibility to exploit this relationship to develop a new therapeutic strategy for the treatment of Notch3 overexpressing tumors which rely on Notch3 protein function to survive and spread to the secondary organ.

Research products

11573/1693986 - 2024 - pH-sensitive niosomes for ATRA delivery. A promising approach to inhibit Pin1 in high-grade serous ovarian cancer
Giuli, Maria Valeria; Hanieh, Patrizia Nadia; Forte, Jacopo; Fabiano, Maria Gioia; Mancusi, Angelica; Natiello, Bianca; Rinaldi, Federica; Del Favero, Elena; Grazia Ammendolia, Maria; Marianecci, Carlotta; Checquolo, Saula; Carafa, Maria - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF PHARMACEUTICS (Elsevier BV:PO Box 211, 1000 AE Amsterdam Netherlands:011 31 20 4853757, 011 31 20 4853642, 011 31 20 4853641, EMAIL: nlinfo-f@elsevier.nl, INTERNET: http://www.elsevier.nl, Fax: 011 31 20 4853598) pp. - - issn: 0378-5173 - wos: WOS:001133086100001 (1) - scopus: (0)

11573/1723855 - 2024 - Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery
Renzi, Serena; Digiacomo, Luca; Pozzi, Daniela; Quagliarini, Erica; Vulpis, Elisabetta; Giuli, Maria Valeria; Mancusi, Angelica; Natiello, Bianca; Pignataro, Maria Gemma; Canettieri, Gianluca; Di Magno, Laura; Pesce, Luca; De Lorenzi, Valentina; Ghignoli, Samuele; Loconte, Luisa; Montone, Carmela Maria; Laura Capriotti, Anna; Laganà, Aldo; Nicoletti, Carmine; Amenitsch, Heinz; Rossi, Marco; Mura, Francesco; Parisi, Giacomo; Cardarelli, Francesco; Zingoni, Alessandra; Checquolo, Saula; Caracciolo, Giulio - 01a Articolo in rivista
paper: NATURE COMMUNICATIONS (London: Nature Publishing Group-Springer Nature) pp. 1-20 - issn: 2041-1723 - wos: (0) - scopus: (0)

11573/1615334 - 2022 - Opsonin-deficient nucleoproteic corona endows unPEGylated liposomes with stealth properties in vivo
Giulimondi, F.; Vulpis, E.; Digiacomo, L.; Giuli, M. V.; Mancusi, A.; Capriotti, A. L.; Lagana, A.; Cerrato, A.; Zenezini Chiozzi, R.; Nicoletti, C.; Amenitsch, H.; Cardarelli, F.; Masuelli, L.; Bei, R.; Screpanti, I.; Pozzi, D.; Zingoni, A.; Checquolo, S.; Caracciolo, G. - 01a Articolo in rivista
paper: ACS NANO (Washington, DC : American Chemical Society) pp. 2088-2100 - issn: 1936-0851 - wos: WOS:000746639100001 (38) - scopus: 2-s2.0-85123925991 (41)

11573/1612769 - 2021 - Notch signaling in female cancers. A multifaceted node to overcome drug resistance
Giuli, M. V.; Mancusi, A.; Giuliani, E.; Screpanti, I.; Checquolo, S. - 01g Articolo di rassegna (Review)
paper: CANCER DRUG RESISTANCE (Alhambra CA: OAE Publishing Inc., 2018-) pp. 805-836 - issn: 2578-532X - wos: WOS:000849619900006 (8) - scopus: 2-s2.0-85117929405 (8)

11573/1344899 - 2019 - Molecular basis of Notch3-Pin1 functional crosstalk in aggressive female tumors: therapeutic targeting implications in ovarian cancer treatment
Giuli, Mv; Giuliani, E; Mancusi, A; Franciosa, G; Olsen, Jv; Screpanti, I; Checquolo, S - 04d Abstract in atti di convegno
conference: SIPMeT Young Meeting (Firenze, Italy)
book: PATHOBIOLOGY: FROM MOLECULAR DISEASE TO CLINICAL APPLICATION - ()

11573/1344900 - 2019 - Notch3-Pin1 crosstalk in ovarian cancer: from molecular mechanism dissection to therapeutic application
Giuli, Mv; Giuliani, E; Mancusi, A; Franciosa, G; Olsen, Jv; Screpanti, I; Checquolo, S - 04d Abstract in atti di convegno
conference: The XI Notch meeting (Athens, Greece)
book: The XI Notch meeting - ()

11573/1344902 - 2019 - Getting insights into Pin1-Notch3 functional crosstalk in ovarian cancer
Giuli, Mv; Giuliani, E; Mancusi, A; Franciosa, G; Olsen, Jv; Screpanti, I; Checquolo, S - 04d Abstract in atti di convegno
conference: 4Th ANNUAL MEETING OF ALLIANCE AGAINST CANCER (ACC) (Roma, Italy)
book: NEW TECHNOLOGIES TO FIGHT CANCER - ()

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