Saula Checquolo Curriculum Vitae scientifico professionale

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Rome, 05-08-2021

Part I – General Information

Full Name Saula Checquolo Citizenship Italian

E-mail [email protected]

Part II – Education

Type Year Institution Notes (Degree, Experience,…)

U n i v e r s i t y graduation

2000 Department of Experimental Medicine - “ Sapienza”

University of Rome - Italy

Master's Degree in Biological Sciences cum lode - Thesis Title: “Il topo transgenico per Notch3 come modello di c o m p r o m i s s i o n e d e l differenziamento timocitario a livello dello stadio pre-T”

Licensure 2001 University of Tuscia, Viterbo, Italy

Professional qualification in Biologist

PhD studies 2000- 2004

Department of Experimental Medicine - “ Sapienza”

PhD in Immunological

Sciences - XVI cycle - Thesis Title: “Il complesso del pre- TCR come integratore dei meccanismi di traduzione coinvolti nella linfomagenesi T”

P o s t - d o c t o r a l studies

2005 Department of Experimental Medicine - “ Sapienza”

Post-doc Fellow (AIRC) ALL. B

Decreto Rettore Università di Roma “La Sapienza” n 2066/2021 del 28/07/2021

Procedura valutativa per la copertura di n. 1 posto di Professore Universitario di seconda fascia per il Settore concorsuale 06/A2 – Settore scientifico-disciplinare MED/04 presso il Dipartimento di

Scienze e Biotecnologie Medico-Chirurgiche – Facoltà di Farmacia e Medicina.

Codice concorso 2021PAR032

Saula Checquolo

Curriculum Vitae scientifico professionale

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P o s t - d o c t o r a l studies

2006- 2008

Department of Experimental Medicine - “ Sapienza”

Post-doc Fellow (FIRC)

Researcher 2008-

present

Department of Medico- S u r g i c a l S c i e n c e s a n d Biotechnology - “Sapienza”

Assistant Professor - SSD MED/04

ASN 2018-

present

Italian Ministry of Education, University and Research (MIUR) - ANVUR

ASN 06/N1 SSD MED46 (for Associate Professor)

ASN 2019-

present

Italian Ministry of Education, University and Research (MIUR) - ANVUR

ASN 06/A2 SSD MED04 (for Associate Professor)

Part III – Appointments

IIIA – Academic Appointments

Start End Institution Position

2020 present “Sapienza” University of Rome - Italy Member of the Faculty Committee 2017 present “Sapienza” University of Rome - Italy Faculty Member of the PhD

program in “Molecular Medicine”

2016 2017 “Sapienza” University of Rome - Italy Member of “Sapienza” Research Committee

2012 2012 “Sapienza” University of Rome - Italy Member of the Academic Board of the PhD program in "Experimental Medicine", XXVII cycle

2011 2014 “Sapienza” University of Rome - Italy Member of the Academic Board of the PhD program in "Innovative technologies in translational medicine", XXVII cycle

IIIB – Other Appointments

Start End Institution Position

2018 present Editorial board of international scientific journals: Journal of Experimental & Clinical Cancer Research, Journal of Hematology &

Oncology, Frontiers, Cellular &

Molecular Immunology, BioMed Research International, Biomarkers in Medicine, Therapeutic Delivery.

Referee

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2012 present MIUR: Italian Ministry of

Education, University and Research

Membership of Referee Institute - CINECA

2006 present “Sapienza” University of Rome - Italy - Molecular Oncology lab

Students (12), PhD Student (7) and Post-doc (2) training activities in Research

2013 present ABCD (Associazione di Biologia Cellulare e del Differenziamento) - AICC (Associazione Italiana Coltura Cellulare) - SIPMET (Società Italiana di Patologia e Medicina T r a s l a z i o n a l e ) - N o t c h I T

“Proteomics in Notch signaling”

Oral and poster presentations to national congress

2011 present Notch meetings (Athen, Greece) - FEBS- EMBO meeting ( Paris, France) - Copenaghen Bioscience C o n f e r e n c e s ( C o p e n a g h e n , Denmark) - ESF-EMBO Research Conference (Pultusk, Polonia)

Oral and poster presentations to international congress

Part IV – Teaching experience

Year Institution Lecture/Course

2019- present

“Sapienza” University POLO PONTINO - Italy

of Rome - “ G e n e r a l P a t h o l o g y a n d Pathophysiology” (code: 10589847) for Master’s Degree program in Medicine and Surgery E - LM41.

2019- present

of Rome - “General Pathology” (as part of the integrated course of Cellular and Molecular Basis of Life - code: 1051496) for Bachelor’s Degree program in Orthopaedics techniques - L/SNT3.

2008- present

of Rome - “General and Clinical Pathology” (as part of the integrated course of Pathophysiological basis of the diseases - code: 1047790) for Bachelor’s Degree program in Orthopaedics techniques - L/SNT2.

Part V - Society memberberships, Awards and Honors Year Title

2013- present

Membership of SIPMET (Società Italiana di Patologia e Medicina Traslazionale) 2006- Winner of Post-doc Fellowship - FIRC (Federazione Italiana per la Ricerca sul 2008 Cancro)

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2005 Winner of Post-doc Fellowship - AIRC (Associazione Italiana per la Ricerca sul Cancro)

Part VI - Funding Information [grants as PI-principal investigator or I-investigator]

Year Title Program Grant value

2 0 2 0 - present

Dissecting the role of the Nijmegen breakage syndrome p r o t e i n i n S H H - d e p e n d e n t tumorigenesis. (Role: I)

U n i v e r s i t y S c i e n t i f i c R e s e a r c h f u n d i n g “ Sapienza” University, code:

RG120172B82DC503

€ 63.787

2 0 1 9 - present

Notch3-Pin1 crosstalk in ovarian cancer: from molecular mechanism d i s s e c t i o n t o t h e r a p e u t i c application. (Role: PI)

RM11916B796B4F3D

€ 10.740

2 0 1 9 - present

D i s s e c t i n g t h e m o l e c u l a r mechanisms underlying the pathogenesis of acute myeloid leukaemia. (Role: I)

I t a l i a n M i n i s t r y o f Education, University and Research (MIUR) - PRIN - B A N D O 2 0 1 7 c o d e : 2017XCXAFZ

€ 134.859

2 0 1 9 - present

PROGEMA - Processi Green per l’estrazione di principi attivi e la depurazione di Matrici di scarto e non. (Role: I)

I t a l i a n M i n i s t r y o f Education, University and Research (MIUR), code:

ARS01_00432

€ 368.680

2 0 1 8 - present

Molecular basis of Notch3-Pin1 functional cross-talk in aggressive female tumors: therapeutic

targeting implications in ovarian cancer treatment. (Role: PI)

RM1181642B5E48E3

€ 33.800

2018- 2019

Grant for general Researcher activities (Role: PI)

Fondo di Finanziamento delle Attività Base di Ricerca - FFABR - Bando 2017 I t a l i a n M i n i s t r y o f Education, University and Research (MIUR)

€ 3.000

2015- 2018

Notch3-EGFR crosstalk in triple negative breast cancers (TNBC):

U n i v e r s i t y S c i e n t i f i c R e s e a r c h f u n d i n g “

€ 8.000 new therapeutic possibilities.

(Role: PI)

Sapienza” University, code:

C26A153A77 2014-

2015

Ruolo della prolina isomerasi Pin1 nello sviluppo e nella progressione della leucemia linfoblastica acuta a cellule T, Notch3-dipendente.

(Role: PI)

C26A14R3X7

€ 5.000

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2013- 2014

Ruolo della prolina isomerasi Pin1 nella regolazione del traffico intracellulare della proteina N o t c h 3 n e l l a l e u c e m i a linfoblastica acuta a cellule T.

(Role: PI)

C26A13RCYY

€ 7.000

2012- 2015

P i a t t a f o r m e t e c n o l o g i c h e innovative per l ’ ingegneria tissutale. (Role: I)

PON01_00829

€ 312.692

2012- 2015

Molecular dissection of Notch3 signaling in T Cell Leukemia:

novel mechanistic insights. (Role:

I)

Investigator Grant AIRC 2012, code: IG13314

€ 360.000

2012- 2013

Studio di fattibilità mirato a dimostrare il possibile ruolo di modificazioni post-traduzionali a carico della proteina Notch3 (N3) n e l l o s v i l u p p o e / o n e l l a progressione della Leucemia Linfoblastica Acuta a cellule T (T- ALL). (Role: PI)

U n i v e r s i t y S c i e n t i f i c Research FARI “ Sapienza”

U n i v e r s i t y , c o d e : C26I12HTKL

€ 6.500

2011- 2015

Sviluppo di molecole capaci di m o d u l a r e vie m e t a b o l i c h e intracellulari redox-sensibili per la prevenzione e la cura di patologie i n f e t t i v e , t u m o r a l i , neurodegenerative e loro delivery m e d i a n t e p i a t t a f o r m e nanotecnologiche. (Role: I)

PON01_001802

€ 500.800

2011- 2012

Ruolo della prolina isomerasi Pin1 nella regolazione del meccanismo di segnalazione della proteina Notch3. (Role: PI)

C26A11BY3F

€ 3.500

2010- 2011

Studio di fattibilità mirato a dimostrare il possibile ruolo di modificazioni epigenetiche nello

U n i v e r s i t y S c i e n t i f i c Research FARI “ Sapienza”

U n i v e r s i t y , c o d e :

€ 7.500

sviluppo e/o nella progressione della Leucemia Linfoblastica Acuta a cellule T (T-ALL). (Role:

PI)

C26I10EA44

2009- 2011

Evaluation of regenerative cell therapy and tissue engineering for ischemic heart disease: regional and global left ventricular quantitative analysis using non- invasive methods. (Role: PI + Responsabile di Unità)

Fondazione Roma, code: not available

€ 1.192.400,00 (total) -

€ 217.800 (Unit)

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2009- 2012

Notch signalling in Development and Pathology. (Role: I)

European Community - F i n a n z i a m e n t o F P 7 - PEOPLE-2007-1-1-ITN ITN (Initial Training Network) , c o d e : N o t c h I T - P I T N - GA-2008-215761.

€ 750.000

2008- 2011

Dissection of Notch-dependent pathways involved in development of T cell leukemia: insights from mouse models. (Role: I)

€ 360.000

2006- 2008

A n a l i s i d e i m e c c a n i s m i trascrizionali nei processi di sopravvivenza, proliferazione e progressione delle emopatie maligne. (Role: I)

I t a l i a n M i n i s t r y o f Education, University and Research (MIUR) - bando P R I N 2 0 0 5 - c o d e : 2005068971

€ 83.800

2005- 2008

Functional relationships between Notch and oncogenic transduction p a t h w a y s i n T c e l l

leukemogenesis”. (Role: I)

€ 417.810

2004- 2008

Novel approaches to pathogenesis, diagnosis and t reatment of autoimmune diseases based on new insignts into thymus- dependent self-tolerance. (Role: I)

European Union - Sixth Framework Program (FP6) I n t e g r a t e d P r o j e c t (FP6-2002-LIFESCIHEALT, proposal N0503410; contract LSHB-CT-2003-503410).

Acronimo: "Eurothymaide"

€ 584.000

2003- 2005

Analisi delle vie di attivazione di N F - k B n e i p r o c e s s i linfoproliferativi T cellulari: ruolo dell'interazione tra Notch3 e il sistema recettoriale per l'antigene (TCR o pre-TCR). (Role: I)

I t a l i a n M i n i s t r y o f Education, University and Research (MIUR) - bando P R I N 2 0 0 3 - c o d e : 2003067871_009

€ 104.900

2001- 2003

R u o l o p a t o g e n e t i c o dell’interazione funzionale tra le vie di trasduzione del segnale di Notch3 e del pre-TCR nella leucemia linfoide T. (Role: I)

I t a l i a n M i n i s t r y o f Education, University and Research (MIUR) - bando P R I N 2 0 0 1 - c o d e : 2001068338_005

€ 95.545

Part VII – Research Activities

Keywords Brief Description

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Cancer -

Notch signaling -

Cancer therapy

Dr Checquolo’s research activity is focused on cancer field, mainly on understanding the mechanistic events of cancer development and progression, both in vitro and in vivo studies. In particular, her research is aimed at investigating in detail the molecular mechanisms that control the role of Notch signaling pathway in hematological and solid tumors, with particular reference to resistance to conventional cancer treatments.

Up to date, any anti-Notch therapies are in routine clinical use, so dissecting new facets of Notch signaling in different cancer contexts becomes an issue of paramount relevance in order to ameliorate the current treatments. To this regard, the main objective of the Dr Checquolo’s research work is the design of alternative therapeutic strategies for the treatment of Notch-overexpressing tumors, which rely on Notch protein (i.e. Notch3) function to survive and spread to secondary organs.

Notch signaling - T cell differentiation - T-ALL

2000-2004. As PhD student in Immunological Sciences, the main interest of Dr. Checquolo has been focused on the analysis of cellular and molecular mechanisms involved in i) T cell and thymocytes differentiation and ii) leukemia development and progression, with particular reference to the identification of new molecular markers of TALLs (i.e. Notch proteins).

As a result of these experiences at the beginning of her career (Bellavia D, PNAS 2002; Talora C, EMBO Rep 2003; Felli MP, Oncogene 2005), Dr Checquolo acquired the technical and training expertises and all the necessary skills for a successful achievement as the team leader of the subsequent research activities, aimed at approaching in depth the molecular mechanisms controlling Notch3 expression and function both in hematological and solid tumors. To this regard, Dr Checquolo fully contributed to the generation, phenotypic and functional characterization of several murine of neoplastic diseases (Notch3 tg mice and Notch3 tg+/pTalpha-/-, Notch3 tg+/PKCtheta-/- Notch3 tg+/Pin1-/- double mutant mice).

Notch3 - T-ALL - pre-TCR

2005-2008. Dr Checquolo continued her research activities as Post-doc focusing her studies on the role of Notch3 in leukemia development and progression, thus providing new insights on Notch3 cross-talk with several pathways involved in molecular mechanisms leukemia-related.

To this regard, her studies conducted in this period helped to reveil the importance of the interplay between Notch3 and pre-TCR signaling in regulating T-ALL development (Checquolo S, Oncogene 2010).

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2008-present. As Assistant Professor of General Pathology of the Faculty of Pharmacy & Medicine of the “Sapienza” University of Rome, Dr. Checquolo’s expertise and qualification in the specific field of research relevant to the proposal is then focused on the: a. Analysis of Notch3 regulation at post-translational level, aimed at identifying potential Notch3 protein regulators; b. Role of the Post-translational modifications (PTMs) events in the Notch3 cross-talk with other signaling pathways, finally aimed at designing new combined targeted therapies. For the achievement of these two interconnected aims, the major scientific accomplishments obtained were:

1) Identification of different PTMs of Notch3 in T-ALL context (Checquolo S, Oncogene 2010; *Palermo R, *Checquolo S et al, Oncogene 2012; Giulia Franciosa et al, Oncogene 2016, S. Checquolo last and corresponding author). *These authors contributed equally to this work). We demostrated that Notch3 can be modified by more than one type of PTM and this event is required for the proper Notch3 function and activity involved in the maintenance and progression of T- ALL.

2) Identification of new cross-talk between Notch3 and other signaling pathways (Diluvio G, Oncogenesis 2018, S. Checquolo last and corresponding author; Giuli et al, Oncogenesis 2020, S. Checquolo last and corresponding author). In 2018, we reported data sustaining a non- canonical role of Notch3 in the Triple Negative Breast Cancer (TNBC), an heterogeneous tumor which displays aggressive phenotype and high relapse rates. We demonstrated that Notch3 is involved in the resistance to anti-EGFR agents, as Notch3 depletion makes the cells sensitive to TKI-gefitinib (Tyrosine Kinase Inhibitor - gefitinib), thus suggesting a potential novel combined therapeutic approach in TNBC-bearing patients treatment. More recently, in 2020, we demonstrated that Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response (UPR), thus suggesting a novel potential combined approach in the treatment of leukemic cells which may rely on UPR for their survival.

3) Identification of Pin1 isomerase as a new regulator of Notch3 protein. We demonstrated that the peptidyl-prolyl cis/trans isomerase Pin1, acting in a phosphorylation-dependent way, is able to positively regulate Notch3 protein in T-ALL context: targeting Pin1-Notch3 axis may influence tumor grade and aggressiveness, thus finally providing a rationale for novel T-ALL therapeutic approaches (Franciosa G, Oncogene 2016). To date, we are investigating in detail the Pin1-Notch3 axis by dissecting the molecular mechanism regulating their cross-talk:

we focus our attention on other proteins (i.e. GSK3beta kinase and WWP2 E3 ligase) whose functional activities upon Notch3, through their "interplay" with Pin1 isomerase, could be closely involved in the regulation of Notch3-dependent ovarian cancer drug resistance to the conventional therapies (Giuli MV, manuscript in preparation).

Notch3 PTMs T-ALL

Female tumors Cancer therapy

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Part VIII – Summary of Scientific Achievements

Product type Number Data Base Start End

P a p e r s [international]

31 https://www.scopus.com 2002 2021

Books [scientific] 1 https://www.scopus.com 2018

Total Impact factor 203,284

Total Citations 1198

Average Citations per Product 37,44

Hirsch (H) index 20

Normalized H index* 1

*H index divided by the academic seniority.

Part IX– Selected Publications

For each publication are reported: title, authors, reference data, journal IF (at the time of publication), citations, and press release (when available). Note: the database Scopus was used to calculate citations.

1. Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.

Maria Valeria Giuli, Giulia Diluvio, Eugenia Giuliani, Giulia Franciosa, Laura Di Magno, Maria Gemma Pignataro, Luca Tottone, Carmine Nicoletti, Zein Mersini Besharat, Giovanna Peruzzi, Maria Pelullo, Rocco Palermo, Gianluca Canettieri, Claudio Talora, Giulia d’Amati, Diana Bellavia, Isabella Screpanti and Saula Checquolo.

Oncogenesis. 2020. Oct 18;9(10):93. Document type: Article.

DOI: 10.1038/s41389-020-00279-7. PMID: 33071287. Publisher: Nature Publishing Group.

IF: 6.73. Citations: 1.

2. Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.

Giuli MV, Giuliani E, Screpanti I, Bellavia D, Checquolo S.

J Oncol. 2019. Jul 11;2019:8707053. Document type: Review.

DOI: 10.1155/2019/8707053. eCollection 2019. PMID: 31379945. Publisher: Cairo - Hindawi Publishing Corporation

3. Kras/ADAM17-dependent Jag1-ICD reverse signaling sustains colorectal cancer progression and chemoresistance.

Pelullo M, Nardozza F, Zema S, Quaranta R, Nicoletti C, Besharat ZM, Felli MP, Cerbelli B, d'Amati, G, Palermo R, Capalbo C, Talora C, Marcotullio LD, Giannini G, Checquolo S*, Screpanti I, Bellavia D*.

Cancer Research. 2019. Nov 1;79(21):5575-5586. Document type: Article.

DOI: 10.1158/0008-5472.CAN-19-0145. Epub 2019 Sep 10. PMID: 31506332. Publisher:

American Association for Cancer Research Inc.

IF: 9.727. Citations: 6. (* co-corresponding authors)

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4. Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells.

Simona Ceccarelli, Francesca Megiorni, Diana Bellavia, Cinzia Marchese, Isabella Screpanti and Saula Checquolo.

Stem Cells Int. 2019. Jan 6;2019:6264931. Document type: Review.

DOI: 10.1155/2019/6264931. eCollection 2019. PMID: 30723507. Publisher: Hindawi Limited.

5. NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest.

G. Diluvio, F. Del Gaudio, M. V. Giuli, G. Franciosa, E. Giuliani, R. Palermo, Z. M.

Besharat, M. G. Pignataro, A. Vacca, G. d'Amati, M. Maroder, C. Talora, C. Capalbo, D.

Bellavia, S. Checquolo.

Oncogenesis. 2018. May 25;7(5):42. Document type: Article.

6. Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression.

G. Franciosa, G. Diluvio, F. D. Gaudio, M. V. Giuli, R. Palermo, P. Grazioli, A. F. Campese, C. Talora, D. Bellavia, G. D'Amati, Z. M. Besharat, C. Nicoletti, C. W. Siebel, L. Choy, A.

Rustighi, G. D. Sal, I. Screpanti, S. Checquolo.

Oncogene. 2016. Sep 8;35(36):4741-51. Document type: Article.

DOI: 10.1038/onc.2016.5. PMID: 26876201. Publisher: Nature Publishing Group.

7. The deregulated expression of miR-125b in acute myeloid leukemia is dependent on the transcription factor C/EBPα.

P Vargas Romero, S Cialfi, R Palermo, C De Blasio, S Checquolo, D Bellavia, S Chiaretti, R Foà, A Amadori, A Gulino, G Zardo, C Talora and I Screpanti.

Leukemia. 2015. Dec;29(12):2442-5. Document type: Article.

DOI: 10.1038/leu.2015.117. Epub 2015 May 18. PMID: 25982911. Publisher: Nature Publishing Group

8. Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia.

V Kumar, R Palermo, C Talora, AF Campese, S Checquolo, D Bellavia, L Tottone, G Testa, E Miele, S Indraccolo, A Amadori, E Ferretti, A Gulino, A Vacca and I Screpanti.

DOI: 10.1038/leu.2014.133. Epub 2014 Apr 14. PMID: 24727676. Publisher: Nature Publishing Group.

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9. Acetylation controls Notch3 stability and function in T cell leukemia.

*Palermo R, *Checquolo S, Giovenco A, Kumar V, Grazioli P, Campese AF, Giorgi A, Ferrara G, Napolitano M, Canettieri G, Schininà ME, Maroder M, Frati L, Gulino A, Vacca A and Screpanti I.

Oncogene. 2012. Aug 16;31(33):3807-17. Document type: Article.

DOI: 10.1038/onc.2011.533. Epub 2011 Nov 28. PMID: 22120716. Nature Publishing Group.

IF: 7.943. Citations: 41. (*co-first authors)

10. Loss of CBL E3-ligase activity in B-lineage childhood acute lymphoblastic leukaemia.

Simone Martinelli*, Saula Checquolo*, Federica Consoli, Emilia Stellacci, Cesare Rossi, Marianna Silvano, Giulia Franciosa, Elisabetta Flex, Carla Cossu, Alessandro De Luca, Robin Foa`, Giovanni Cazzaniga, Andrea Biondi, Isabella Screpanti, Marco Tartaglia.

Br J Haematol. 2012. Oct;159(1):115-9. Document type: Letter.

DOI: 10.1111/j.1365-2141.2012.09245.x. Epub 2012 Jul 27. PMID: 22834886. Publisher:

Blackwell Science Limited.

11. Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype.

Martinelli S, De Luca A, Stellacci E, Rossi C, Checquolo S, Lepri F, Silvano M, Buscherino F, Consoli F, Ferrara G, Digilio MC, Cavaliere ML, van Hagen A, Zampino G, van der Burgt I, Screpanti I, Yntem HGa, Nillesen WM, Savarirayan R, Zenker M, Dallapiccola B, Gelb BD and Tartaglia M.

Am J Hum Genet. 2010. Aug 13;87(2):250-7. Document type: Article.

DOI: 10.1016/j.ajhg.2010.06.015. Epub 2010 Jul 8. PMID: 20619386. Cell Press.

12. Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia.

Checquolo S, Palermo R, Cialfi S, Ferrara G, Oliviero C, Talora C, Bellavia D, Giovenco A, Grazioli P, Frati L, Gulino A, Screpanti I.

Oncogene. 2010. Mar 11;29(10):1463-74. Document type: Article.

DOI: 10.1038/onc.2009.446. Epub 2009 Dec 7. PMID: 19966856. Nature Publishing Group.

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Part X– Complete List of Publications

For each publication are reported: title, authors, reference data, journal IF (at the time of publication), citations, and press release (when available). Note: the database Scopus was used to calculate citations.

1. Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.

Maria Valeria Giuli, Giulia Diluvio, Eugenia Giuliani, Giulia Franciosa, Laura Di Magno, Maria Gemma Pignataro, Luca Tottone, Carmine Nicoletti, Zein Mersini Besharat, Giovanna Peruzzi, Maria Pelullo, Rocco Palermo, Gianluca Canettieri, Claudio Talora, Giulia d’Amati, Diana Bellavia, Isabella Screpanti and Saula Checquolo.

Oncogenesis. 2020. Oct 18;9(10):93. Document type: Article.

2. Current Trends in ATRA Delivery for Cancer Therapy.

Maria Valeria Giuli, Patrizia Nadia Hanieh, Eugenia Giuliani, Federica Rinaldi, Carlotta Marianecci, Isabella Screpanti, Saula Checquolo* and Maria Carafa.

Pharmaceutics. 2020. Jul 28;12(8):707. Document type: Review.

DOI: 10.3390/pharmaceutics12080707. PMID: 32731612. Publisher: MDPI AG.

IF: 4.699. Citations: 8. (* corresponding author)

3. Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.

Giuli MV, Giuliani E, Screpanti I, Bellavia D, Checquolo S.

J Oncol. 2019. Jul 11;2019:8707053. Document type: Review.

DOI: 10.1155/2019/8707053. eCollection 2019. PMID: 31379945. Publisher: Cairo - Hindawi Publishing Corporation.

4. Kras/ADAM17-dependent Jag1-ICD reverse signaling sustains colorectal cancer progression and chemoresistance.

Pelullo M, Nardozza F, Zema S, Quaranta R, Nicoletti C, Besharat ZM, Felli MP, Cerbelli B, d'Amati, G, Palermo R, Capalbo C, Talora C, Marcotullio LD, Giannini G, Checquolo S*, Screpanti I, Bellavia D*.

Cancer Research. 2019. Nov 1;79(21):5575-5586. Document type: Article.

DOI: 10.1158/0008-5472.CAN-19-0145. Epub 2019 Sep 10. PMID: 31506332. Publisher:

American Association for Cancer Research Inc.

IF: 9.727. Citations: 6. (* co-corresponding authors)

5. Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells.

Simona Ceccarelli, Francesca Megiorni, Diana Bellavia, Cinzia Marchese, Isabella Screpanti and Saula Checquolo.

Stem Cells Int. 2019. Jan 6;2019:6264931. Document type: Review.

DOI: 10.1155/2019/6264931. eCollection 2019. PMID: 30723507. Publisher: Hindawi Limited.

6. Histone Modifications Drive Aberrant Notch3 Expression/Activity and Growth in T- ALL.

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L. Tottone, N. Zhdanovskaya, A. Carmona Pestana, M. Zampieri, F. Simeoni, S. Lazzari, V.

Ruocco, M. Pelullo, P. Caiafa, M. P. Felli, S. Checquolo, D. Bellavia, C. Talora, I.

Screpanti, R. Palermo.

Frontiers in Oncology. 2019 Apr 3;9:198. Document type: Article.

DOI: 10.3389/fonc.2019.00198. PMID: 31001470. Publisher: Frontiers Media S.A.

7. PLK1 targets NOTCH1 during DNA damage and mitotic progression.

De Blasio C, Zonfrilli A, Franchitto M, Mariano G, Cialfi S, Verma N, Checquolo S, Bellavia D, Palermo R, Benelli D, Screpanti I, Talora C.

J Biol Chem. 2019. Nov 22;294(47):17941-17950. Document type: Article.

DOI: 10.1074/jbc.RA119.009881. Epub 2019 Oct 9. PMID: 31597699. Publisher: American Society for Biochemistry and Molecular Biology Inc.

8. Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer.

Pelullo M, Zema S, Nardozza F, Checquolo S, Screpanti I, Bellavia D.

Front Genet. 2019. Aug 21;10:711. Document type: Article.

DOI: 10.3389/fgene.2019.00711. eCollection 2019. PMID: 31552081. Publisher: Frontiers Media S.A.

9. Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation.

Laura Antonucci, Laura Di Magno, Davide D'amico, Simona Manni, Silvia Maria Serrao, Fiorella Di Pastena, Rosa Bordone, Zuleyha Nihan Yurtsever, Miriam Caimano,

Marialaura Petroni, Alessandra Giorgi, Maria Eugenia Schininà, John R. Yates Iii, Lucia Di Marcotullio, Enrico De Smaele, Saula Checquolo, Carlo Capalbo, Enzo Agostinelli,

Marella Maroder, Sonia Coni and Gianluca Canettieri.

Int J Oncol. 2019. Feb;54(2):505-514. Document type: Article.

DOI: 10.3892/ijo.2018.4638. Epub 2018 Nov 19. PMID: 30483764. Publisher: Spandidos Publications.

10. NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest.

G. Diluvio, F. Del Gaudio, M. V. Giuli, G. Franciosa, E. Giuliani, R. Palermo, Z. M.

Besharat, M. G. Pignataro, A. Vacca, G. d'Amati, M. Maroder, C. Talora, C. Capalbo, D.

Bellavia, S. Checquolo.

Oncogenesis. 2018. May 25;7(5):42. Document type: Article.

11. Notch signaling as a therapeutic target for Acute Lymphoblastic Leukemia.

Bellavia, Diana, Palermo, Rocco, Felli, Maria Pia, Screpanti, Isabella, Checquolo, Saula.

Expert Opin Ther Targets. 2018. Apr;22(4):331-342. Document type: Review.

DOI: 10.1080/14728222.2018.1451840. Epub 2018 Mar 21. PMID: 29527929. Publisher:

Taylor and Francis Ltd

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12. Maml1 acts cooperatively with Gli proteins to regulate Sonic hedgheog signaling pathway.

Roberta Quaranta, Maria Pelullo, Sabrina Zema, Francesca Nardozza, Saula Checquolo, Dieter Matthias Lauer, Francesca Bufalieri, Rocco Palermo, Maria Pia Felli, Alessandra Vacca, Claudio Talora, Lucia Di Marcotullio, Isabella Screpanti, Diana Bellavia.

Cell Death Dis. 2017. Jul 20;8(7):e2942. Document type: Article.

DOI: 10.1038/cddis.2017.326. PMID: 28726779. Publisher: Nature Publishing Group IF: 5.638. Citations: 18.

13. Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression.

G. Franciosa, G. Diluvio, F. D. Gaudio, M. V. Giuli, R. Palermo, P. Grazioli, A. F. Campese, C. Talora, D. Bellavia, G. D'Amati, Z. M. Besharat, C. Nicoletti, C. W. Siebel, L. Choy, A.

Rustighi, G. D. Sal, I. Screpanti, S. Checquolo.

Oncogene. 2016. Sep 8;35(36):4741-51. Document type: Article.

DOI: 10.1038/onc.2016.5. PMID: 26876201. Publisher: Nature Publishing Group.

14. RET mutation and increased angiogenesis in medullary thyroid carcinomas.

Verrienti Antonella, Tallini Giovanni, Colato Chiara, Boichard Amélie, Checquolo Saula, Pecce Valeria, Sponziello Marialuisa, Rosignolo Francesca, de Biase Dario, Rhoden Kerry, Casadei Gian Piero, Russo Diego, Visani Michela, Acquaviva Giorgia, Ferdeghini Marco, Filetti Sebastiano, Durante Cosimo.

Endocr Relat Cancer. 2016. Aug;23(8):665-76. Document type: Article.

DOI: 10.1530/ERC-16-0132. Epub 2016 Jul 8. PMID: 27402614. Publisher: BioScientifica Ltd.

15. The deregulated expression of miR-125b in acute myeloid leukemia is dependent on the transcription factor C/EBPα.

P Vargas Romero, S Cialfi, R Palermo, C De Blasio, S Checquolo, D Bellavia, S Chiaretti, R Foà, A Amadori, A Gulino, G Zardo, C Talora and I Screpanti.

DOI: 10.1038/leu.2015.117. Epub 2015 May 18. PMID: 25982911. Publisher: Nature Publishing Group

16. Loss of Notch1-dependent p21Waf1/Cip1 expression influences the Notch1 outcome in tumorigenesis.

Samantha Cialfi, Rocco Palermo, Sonia Manca, Carlo De Blasio, Paula Vargas Romero, Saula Checquolo, Diana Bellavia, Daniela Uccelletti, Michele Saliola, Angelo

D'Alessandro, Lello Zolla, Alberto Gulino, Isabella Screpanti and Claudio Talora.

Cell Cycle. 2014. 13(13):2046-55. Document type: Article.

DOI: 10.4161/cc.29079. Epub 2014 May 6. PMID: 24801890. Publisher: Taylor and Francis Inc.

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17. Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia.

V Kumar, R Palermo, C Talora, AF Campese, S Checquolo, D Bellavia, L Tottone, G Testa, E Miele, S Indraccolo, A Amadori, E Ferretti, A Gulino, A Vacca and I Screpanti.

DOI: 10.1038/leu.2014.133. Epub 2014 Apr 14. PMID: 24727676. Publisher: Nature Publishing Group.

18. Notch3/Jagged1 Circuitry Reinforces Notch Signaling and Sustains T-ALL.

Maria Pelullo, Roberta Quaranta, Claudio Talora, Saula Checquolo, Samantha Cialfi, Maria Pia Felli, Geertruy te Kronnie, Chiara Borga, Zein Mersini Besharat, Rocco Palermo, Lucia Di Marcotullio, Anthony J. Capobianco, Alberto Gulino, Isabella Screpanti and Diana Bellavia.

Neoplasia. 2014. Dec;16(12):1007-17. Document type: Article.

DOI: 10.1016/j.neo.2014.10.004. PMID: 25499214. Publisher: Elsevier Inc.

19. Numb-dependent integration of pre-TCR and p53 function in T-cell precursor development.

NM Martin-Blanco, S Checquolo, F Del Gaudio, R Palermo, G Franciosa, L Di Marcotullio, A Gulino, M Canelles and I Screpanti.

Cell Death Dis. 2014. Oct 16;5(10):e1472. Document type: Article.

DOI: 10.1038/cddis.2014.438. PMID: 25321479. Publisher: Nature Publishing Group.

20. The Molecular Basis of Notch Signaling Regulation: A Complex Simplicity.

*R. Palermo, *S. Checquolo, D. Bellavia, C. Talora and I. Screpanti.

Curr Mol Med. 2014. Jan;14(1):34-44. Document type: Review.

DOI: 10.2174/1566524013666131118105216. PMID: 24236458. Publisher: Bentham Sciences.

21. Loss of CBL E3-ligase activity in B-lineage childhood acute lymphoblastic leukaemia.

Simone Martinelli*, Saula Checquolo*, Federica Consoli, Emilia Stellacci, Cesare Rossi, Marianna Silvano, Giulia Franciosa, Elisabetta Flex, Carla Cossu, Alessandro De Luca, Robin Foa`, Giovanni Cazzaniga, Andrea Biondi, Isabella Screpanti, Marco Tartaglia.

Br J Haematol. 2012. Oct;159(1):115-9. Document type: Letter.

DOI: 10.1111/j.1365-2141.2012.09245.x. Epub 2012 Jul 27. PMID: 22834886. Publisher:

Blackwell Science Limited.

22. Glucocorticoid sensitivity of T-cell lymphoblastic leukemia/lymphoma is associated with glucocorticoid receptor-mediated inhibition of Notch1 expression.

S Cialfi, R Palermo, S Manca, S Checquolo, D Bellavia, M Pelullo, R Quaranta, C Dominici, A Gulino, I Screpanti and C Talora.

Leukemia. 2013. Feb;27(2):485-8. Document type: Letter.

DOI: 10.1038/leu.2012.192. Epub 2012 Jul 13. PMID: 22846929. Nature Publishing Group.

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23. Acetylation controls Notch3 stability and function in T cell leukemia.

*Palermo R, *Checquolo S, Giovenco A, Kumar V, Grazioli P, Campese AF, Giorgi A, Ferrara G, Napolitano M, Canettieri G, Schininà ME, Maroder M, Frati L, Gulino A, Vacca A and Screpanti I.

Oncogene. 2012. Aug 16;31(33):3807-17. Document type: Article.

DOI: 10.1038/onc.2011.533. Epub 2011 Nov 28. PMID: 22120716. Nature Publishing Group.

24. Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype.

Martinelli S, De Luca A, Stellacci E, Rossi C, Checquolo S, Lepri F, Silvano M, Buscherino F, Consoli F, Ferrara G, Digilio MC, Cavaliere ML, van Hagen A, Zampino G, van der Burgt I, Screpanti I, Yntem HGa, Nillesen WM, Savarirayan R, Zenker M, Dallapiccola B, Gelb BD and Tartaglia M.

Am J Hum Genet. 2010. Aug 13;87(2):250-7. Document type: Article.

DOI: 10.1016/j.ajhg.2010.06.015. Epub 2010 Jul 8. PMID: 20619386. Nature Publishing Group.

25. Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia.

Checquolo S, Palermo R, Cialfi S, Ferrara G, Oliviero C, Talora C, Bellavia D, Giovenco A, Grazioli P, Frati L, Gulino A, Screpanti I.

Oncogene. 2010. Mar 11;29(10):1463-74. Document type: Article.

DOI: 10.1038/onc.2009.446. Epub 2009 Dec 7. PMID: 19966856. Cell Press.

26. Notch3 and pTa/pre-TCR sustain the in vivo function of naturally occurring regulatory T cells.

Campese AF, Graziali P, Colantoni S, Anastasi E, Mecarozzi M, Checquolo S, De Luca G, Bellavia D, Frati L,Gulino A and Screpanti I.

Int Immunol. 2009. Jun;21(6):727-43. Document type: Article.

DOI: 10.1093/intimm/dxp042. Epub 2009 May 21. PMID: 19461123. Publisher: Oxford academic.

27. Notch3: From subtle structural differences to functional diversity.

Bellavia D, Checquolo S, Campese AF, Felli MP, Gulino A, Screpanti I.

Oncogene. 2008. Sep 1;27(38):5092-8. Document type: Review.

DOI: 10.1038/onc.2008.230. PMID: 18758477. Nature Publishing Group.

28. PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia.

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Felli, M.P., Vacca, A., Calce, A., Bellavia, D., Campese, A.F., Grillo, R., Di Giovine, M., Checquolo S., Talora, C., Palermo, R., Di Mario, G., Frati, L., Gulino, A., and Screpanti, I.

Oncogene. 2005. Feb 3;24(6):992-1000. Document type: Article.

DOI: 10.1038/sj.onc.1208302. PMID: 15592506. Publisher: Nature Publishing Group.

29. Expression of Activated Notch3 in Transgenic Mice Enhances Generation of T Regulatory Cells and Protects against Experimental Autoimmune Diabetes.

Anastasi E, Campese AF, Bellavia D, Bulotta A, Balestri A, Pascucci M, Checquolo S, Gradini R, Lendahl U, Frati L, Gulino A, Di Mario U and Screpanti I.

J Immunol. 2003. Nov 1;171(9):4504-11. Document type: Article.

DOI: 10.4049/jimmunol.171.9.4504. PMID: 14568923. Publisher: American Association of Immunologists.

30. Pre-TCR-triggered ERK signalling-dependent downregulation of E2A activity in Notch3-induced T-cell lymphoma.

Talora C, Campese AF, Bellavia D, Pascucci M, Checquolo S, Groppioni M, Frati L, von Boehmer H, Gulino A and Screpanti I.

EMBO Rep. 2003. Nov;4(11):1067-72. Document type: Article.

DOI: 10.1038/sj.embor.embor7400013. Epub 2003 Oct 17. PMID: 14566327. Publisher:

Oxford University Press.

31. Combined expression of pTα and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis.

Bellavia D, Campese, A.F, Checquolo S, Balestri A, Biondi A, Cazzaniga G, Lendahl U, Feeling HJ, Hayday AC, Frati L, von Boehmer H, Gulino A and Screpanti I.

Proc Natl Acad Sci U S A. 2002. Mar 19;99(6):3788-93. Document type: Article.

DOI: 10.1073/pnas.062050599. Epub 2002 Mar 12. PMID: 11891328. Publisher: United States National Academy of Sciences.

Books

The Notch3 Receptor and Its Intracellular Signaling Dependent Oncogenic

Mechanisms. In: Borggrefe T., Giaimo B. (eds) Molecular Mechanisms of Notch Signaling.

Advances in Experimental Medicine and Biology.

Bellavia D., Checquolo S., Palermo R., Screpanti I.

Adv Exp Med Biol. 2018. 1066:205-222. Document type: Chapter in book.

DOI: 10.1007/978-3-319-89512-3_10. PMID: 30030828. Publisher: Springer, Cham IF: 2.126. Citations: 4.

Rome, 05/08/2021 Signature