RAFFAELE STRIPPOLI

RAFFAELE STRIPPOLI

Curriculum Vitae

Education
University graduation: 1997 Sapienza University Medicine, full marks and honors
Specialty: 2002 Sapienza University Residency in Laboratory medicine, 70/70 and L
PhD: 2007 Sapienza University PhD in Immunology

Appointments
– Academic Appointments
01/09/2013-30/08/2018 Sapienza University Dipartimento di Biotecnologie cellulari ed Ematologia Assistant Professor (RTDA)
01/09/2018-Now Sapienza University Dipartimento di Medicina Molecolare Assistant Professor Tenure Track (RTDB)

– Other Appointments
01-02-2002 30-05-2002 Fulbright Commission Fulbright Fellowship (spent at Butcher lab Stanford University, Palo Alto)
01-07-2005 30-06-2006 FIRC foundation FIRC Fellowship (spent at CNIC, Madrid, Del Pozo lab)
01-01-2007 30-01-2009 Ministerio Economia y Competitividad, Fundaciòn CNIC Carlos III, Madrid Spain Three years Rìo Hortega Fellowship (for MD Residents), (spent at CNIC, Madrid, Del Pozo lab)
01-09-2008 30-08-2012 IRCCS Bambino Gesù Rome Italy Research Fellowship, Lab De Benedetti

Society memberships
2000 SIICA Società Italiana di Immunologia Immunologia Clinica ed Allergologia
2007 TEMTIA the EMT International Association
2008 Pres, Pediatric Rheumatology European Society
2015 ABCD, Associazione di Biologia Cellulare e del Differenziamento

Awards and Honors
2009 Disease Models and Mechanisms (DMM) research presentation Grant
2014 Invited Speaker at the International Symposium on Translational Approaches to Autoinflammatory Diseases 15th + 16th May 2014, Münster Germany
2019 Invited Speaker, Centro Nacional de Biologia Molecular (CBM) Severo Ochoa (Madrid, Spain) cycle of conferences 2018/2019

Evaluation of Research projects and editorial activity
2011 Independent evaluator of Greek National Action 'Cooperation 2011' (Evaluation of a competitive research project in cancer cell apoptosis from European Union/ Ministry of Education, Life Long Learning and Religious Affairs cofounding)
2016 Independent evaluator of peer review of Application for Kidney Research UK
2016 Lead Guest Editor, Mediators of Inflammation
2017 Lead Guest Editor, Frontiers in Pharmacology
2018 Guest Editor, Oxidative Medicine and Cellular Longevity
2019 Guest Editor, Journal of Oncology

Peer Review activity
2010-2019 Peer Review activity traced in Publons since 2013 (https://publons.com/author/1192573/raffaele-strippoli#profile) for Journal of Biological Chemistry, Cell Death and Differentiation, Journal of Cell Science, PloS One, Translational Research, Journal of Rheumatology, Pharmaceutical Biology, Laboratory Investigation, Cellular Physiology and Biochemistry; American Journal of Nephrology, Pharmacological Reports, World Journal Gastroenterology, Scientific Reports, the Journal of Pathology, Oncotarget, Biochimica and Biophysica acta (BBA), FEBS journal, Frontiers of Medicine, Frontiers in Pharmacology, Frontiers of Medicine, BMC Nephrology. Journal of Cell Science,

Research Activities
I am interested in molecular mechanisms controlling the induction/reversal of Epithelial to Mesenchymal Transition (EMT) and fibrosis. In particular, I focused my investigation in intracellular mechanisms controlling the plasticity of mesothelial cells in inflammatory/fibrogenic conditions. I and collaborators elucidated the role of NF-kappaB/ERK1/2/Snail axis in EMT induction/reversal and we analyzed p38-NF-kB and ERK1/2-SMADs cross talks. In a recent study, we elucidated the role of Caveolin1 in limiting EMT induction due to repression of MEK/ERK pathway in in vitro and in-vivo models.
I am presently involved in research projects related to mechanical regulation of EMT and to the control of EMT induction/reversal by epigenetic factors in mesothelial cells and in other projects aimed to characterize novel proteins relevant for EMT dynamics.
Moreover, I have been implicated in the study of pathogenetic mechanisms of rheumatic inflammatory diseases, such as juvenile idiopathic arthritis (JIA) and macrophage activation syndrome (MAS/HLH). Taking advantage of both murine (IL-6 transgenic mice) and cellular (mononuclear cells from synovial fluid and synovial fibroblasts) models, we analysed interrelations between cytokines, especially IL-6, and Toll-like receptor (TLR) ligands in the genesis of the inflammatory response, leading eventually to fibrotic damage. We found that a cooperation between TLR- and cytokine-induced signals enhances the activity of both mononuclear and stromal cells, leading to an exacerbation of the inflammatory response. These discoveries contributed to constitute the rational for the ongoing introduction of new biologic drugs, such as anti-IL-6 and anti-IFNgamma mAbs, for treatment of JIA and other rheumatic diseases.

Keywords
Epithelial to Mesenchymal transition (EMT), fibrosis, mesothelial cells, signalling pathways, toll like receptors, cytokines, macrophage activation syndrome (MAS)

Summary of Scientific Achievements

Patents 2
Patent 1 Use of tak1 inhibitors in the prevention and treatment of peritoneal membrane failure P201031439 ES1997.8 September 28th 2010 https://www.google.com/patents/WO2012042091A3?cl=en 2010
Patent 1 Mek 1/2 inhibitors for the treatment of peritoneal fibrosis PCT/ES2009/070348 https://encrypted.google.com/patents/WO2010020703A1?cl=zh 2009

Papers
Total number of products (papers) 34 Scopus 2000-2019
Total Citations 1002 (Scopus)
Average Citations per Product 29.5 (Scopus)
Hirsch (H) index 18 (Scopus)

Publications
1) Stazi G, Battistelli C, Piano V, Mazzone R, Marrocco B, Marchese S, Louie SM, Zwergel C, Antonini L, Patsilinakos A, Ragno R, Viviano M, Sbardella G, Ciogli A, Fabrizi G, Cirilli R, Strippoli R, Marchetti A, Tripodi M, Nomura DK, Mattevi A, Mai A, Valente S. Eur J Med Chem. 2019 Feb 1;163:722-735. doi: 10.1016/j.ejmech.2018.11.050. Development of alkyl glycerone phosphate synthase inhibitors: Structure-activity relationship and effects on ether lipids and epithelial-mesenchymal transition in cancer cells. (IF:4.8)
2) Moreno-Vicente R, Pavón DM, Martín-Padura I, Català-Montoro M, Díez-Sánchez A, Quílez-Álvarez A, López JA, Sánchez-Álvarez M, Vázquez J, Strippoli R, Del Pozo MA. Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP. Cell Rep. 2018 Nov 6;25(6):1622-1635.e6. doi: 10.1016/j.celrep.2018.10.024. (IF:8.03))
3) Muriel O, Sánchez-Álvarez M, Strippoli R, Del Pozo MA. Role of the Endocytosis of Caveolae in Intracellular Signaling and Metabolism Prog Mol Subcell Biol. 2018;57:203-234. doi: 10.1007/978-3-319-96704-2_8. (IF:n.d.)
4)Rossi L, Battistelli C, de Turris V, Noce V, Zwergel C, Valente S, Moioli A, Manzione A, Palladino M, Bordoni V, Domenici A, Menè P, Mai A, Tripodi M, Strippoli RHDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal. Sci Rep. 2018 May 31;8(1):8492. doi: 10.1038/s41598-018-26319-2. (IF:4.3)
5)Pellinen T, Blom S, Sánchez S, Välimäki K, Mpindi JP, Azegrouz H, Strippoli R, Nieto R, Vitón M, Palacios I, Turkki R, Wang Y, Sánchez-Alvarez M, Nordling S, Bützow A, Mirtti T, Rannikko A, Montoya MC, Kallioniemi O, Del Pozo MA. ITGB1-dependent upregulation of Caveolin-1 switches TGFβ signalling from tumour-suppressive to oncogenic in prostate cancer. Sci Rep. 2018 Feb 5;8(1):2338. doi: 10.1038/s41598-018-20161-2. (IF:4.3)
6)Magistri* P, Battistelli* C, Strippoli R*, Petrucciani N, Pellinen T, Rossi L, D'Angelo F, Tripodi G, Ramacciato G, Nigri G SMO inhibition modulates cellular plasticity and invasiveness in colorectal cancer. Frontiers in Pharmacology, Front Pharmacol. 2018 Feb 2;8:956. doi: 10.3389/fphar.2017.00956. eCollection 2017 (IF 4.400 *shared autorship
7)G Prencipe, I Caiello, A Pascarella, AA Grom, C Bracaglia, L Chatel, Ferlin WG, Marasco E, Strippoli R, de Min C, De Benedetti F. Neutralization of interferon-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome Journal of Allergy and Clinical Immunology Aug 11. pii: S0091-6749(17)31277-0. doi: 10.1016/j.jaci.2017.07.021 (IF: 13.081) Press release: http://www.sanita24.ilsole24ore.com/art/medicina-e-ricerca/2017-09-01/ma...
8)Strippoli R, Echarri A, del Pozo MA Cell-Based Assays to Study ERK Pathway/Caveolin1 Interactions Methods in Molecular Biology 2017;1487:163-174 PMID:27924566 (IF:n.d.)
9) Santangelo L., Battistelli C., Montaldo C., Citarella F., Strippoli R. and Cicchini C.."Functional roles and therapeutic applications of exosomes in hepatocellular carcinoma" BioMed Research International ;2017:2931813. doi: 10.1155/2017/2931813. (IF:2.476)
10) De Santis Puzzonia M, Cozzolino AM, Grassi G, Bisceglia F, Strippoli R, Guarguaglini G, Citarella F, Sacchetti B, Tripodi M, Marchetti A, Amicone L. TGFbeta Induces Binucleation/Polyploidization in Hepatocytes through a Src-Dependent Cytokinesis Failure. PLoS One. 2016 Nov 28;11(11):e0167158. doi: 10.1371/journal.pone.0167158. (IF:2.806)
11) T.Oranges, A. Insalaco, A. Diociaiuti, C. Carnevale, R. Strippoli, G. Zambruno, P. Tomà, M. El Hachem "Severe osteoarticular involvement in isotretinoin-triggered acne fulminans: two cases successfully treated with anakinra" Journal of European Academy of Dermatology(2016) (IF: 3.528)
12)Strippoli R, Moreno-Vicente R., Battistelli C., Cicchini C., Noce V, Amicone L, Marchetti A, Miguel del Pozo MA, and Tripodi M.Molecular Mechanisms Underlying Peritoneal EMT and Fibrosis, Stem Cells International
Volume 2016 (2016) (IF: 3.540)
13)Cifaldi L, Prencipe G, Caiello I, Bracaglia C, Locatelli F, De Benedetti F, Strippoli R Inhibition of Natural Killer Cell Cytotoxicity by Interleukin-6: Implications for the Pathogenesis of Macrophage Activation Syndrome. Arthritis and Rheumatology 2015 Nov;67(11):3037-46 (IF: 8.955)
14)Strippoli R, Loureiro J, Moreno V, Benedicto I, Pérez Lozano ML, Barreiro O, Pellinen T, Minguet S, Foronda M, Osteso MT, Calvo E, Vázquez J, López Cabrera M, del Pozo MA. Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis. EMBO Mol Med. 2014 Dec 30;7(1):102-23 (IF: 9.547)
15)Caiello I, Minnone G, Holzinger D,Vogl T, Prencipe G, Manzo A, De Benedetti F, Strippoli R IL-6 amplifies TLR mediated cytokine and chemokine production: implications for the pathogenesis of rheumatic inflammatory diseases PLoS ONE, 2014 Oct 1;9(10):e107886. (IF:3.23) 16) Prencipe G, Minnone G, Strippoli R, De Pasquale L, Stefania Petrini S, Caiello I, Manni L, De Benedetti L and Bracci-Laudiero L Nerve Growth Factor through TrkA down-regulates inflammatory response inhuman monocytes after Toll-like receptor stimulation. Journal of Immunology 2014 Apr 1;192(7):3345-54 (IF: 4.92)
17) Petrini S, Bertini E, De Benedetti F, Frank C, Coccetti M, Minnone G, Aiello C, Cutarelli A, Ambrosini A, Lanciotti AM, Brignone S, Strippoli R, Bracci-Laudiero L Monocytes and macrophages as biomarkers for the diagnosis of Megalencephalic leukoencephalopathy with subcortical cysts. Molecular and Cellular Neuroscience 2013 Sep;56:307-21 (IF:3.73) 18)Strippoli R., Caiello I, De Benedetti F Reaching the threshold: a multilayer pathogenesis of macrophage activation syndrome.. The Journal of Rheumatology, 2013 Jun;40(6):761-7. (IF: 3.17)
19)Strippoli R, Benedicto I, Perez Lozano ML , Pellinen T, Sandoval P, Lopez-Cabrera M and del Pozo MA Inhibition of transforming growth factor-activated kinase 1 (TAK1) blocks and reverses epithelial to mesenchymal transition of mesothelial cells. PLoS ONE 01/2012; 7(2):e31492 (IF:3.73)
20)Strippoli R, Carvello F, Scianaro R, De Pasquale L, Vivarelli M, Petrini S, Bracci-Laudiero L, and De Benedetti F. (2012)Chronic exposure to Interleukin-6 amplifies the response to Toll-like receptor ligands: implication on the pathogenesis of macrophage activation syndrome. Arthritis Rheumatism 2012 (IF: 7.47)
21)Strippoli R., Benedicto I., Foronda M., Perez-Lozano M.L., Sánchez-Perales S., López Cabrera M., and del Pozo M.Á. (2010) p38 maintains E-cadherin expression by modulating TAK1-NF-kappaB during epithelial-to mesenchymal transition. Journal of Cell Science 123, 4321-4331. (IF: 6.29)
22)Strippoli R, Benedicto I, Pérez Lozano ML, Cerezo A, López-Cabrera M, Del Pozo MA. (2008) Epithelial-to-mesenchymal transition of peritoneal mesothelial cells is regulated by an ERK/NF-kappaB/Snail1 pathway. Dis Model Mech. 1, 264-274. (IF: 3.304) Press release: http://www.agenciasinc.es/Noticias/Cientificos-espanoles-identifican-los...
23) D Holzinger, N Fall, A Grom, W de Jager, S Vastert, R Strippoli, C Bracaglia, E Sundberg, A Horne, S Ehl, F De Benedetti, K Beutel, and D Foell S100A12 as diagnostic tool in the differential diagnosis of sJIA associated MAS vs. hereditary or acquired HLH Pediatr Rheumatol Online J. 2015; 13(Suppl 1): O64. Published online 2015 Sep 28. doi: 10.1186/1546-0096-13-S1-O64 (IF: 1.82
24)Toschi, E., Bacigalupo, I., Strippoli, R., Cereseto, A., Falchi, M., Sgadari, C., Barillari, G., Nappi, F., Mainiero, F. and Ensoli, B. (2006) HIV-1 Tat controls endothelial cell cycle progression through the activation of the Ras/ERK MAPK signaling pathway. Molecular Biology of the Cell, 17, 1985-1994. (IF: 6.562)
25)Colombara, M., Antonini, V., Riviera, A.P., Mainiero, F., Strippoli, R., Poffe, O., Brutti, N., Tridente, G., and Ramarli, D. (2005) Misruled MAPK activity leads to IL-6 and Rantes over-expression in epithelial cells of myastenic thymus. Journal of Immunology. 175. 7021-7028. (IF: 6.84)
26)Casilli, F., Bianchini, A., Gloaguen, I., Biordi, L., Alesse, E., Festuccia, C., Cavalieri, B., Strippoli, R., Cervellera, M.N., Di Bitondo, R., Ferretti, E., Mainiero, F., Bizzarri, C., Colotta F., and Bertini, R.(2005) Inhibition of Interleukin-8 (CXCL8/IL-8) responses by Repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2. Biochemical Pharmacology. 69, 385-394. (IF: 4.01 )
27)Bertini, R., Allegretti, M., Bizzarri, C., Moriconi, A., Locati, M., Zampella, G., Cervellera, M.N., Di Cioccio, V., Cesta, M.C., Galliera, E., Martinez, F.O., Di Bitondo, R., Troiani, G., Sabbatini, V., Anacardio. R., Cutrin, J.C., Cavalieri, B., Mainiero, F., Strippoli, R., Villa, P., Di Girolamo, M., Martin, F., Gentile, M., Santoni, A., Corda, D., Ghezzi, P., Poli, G., Mantovani, A., Colotta, F. (2004) A new class of non-competitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc. Natl. Acad. Sci. USA. 101, 11791-11796 (IF: 9.67)
28)Di Cioccio, V., Strippoli, R., Bizzarri, C., Troiani, G., Cervellera, M.N., Gloaguen, I., Colagrande, A., Cattozzo, E.M., Pagliei, S., Santoni, A., Colotta, F., Mainiero, F., and Bertini, R. (2004) Key role of Proline-Rich Tyrosine Kinase 2 in Interleukin 8 (CXCL8/IL-8)-mediated human neutrophil chemotaxis. Immunology. 111, 407-415 (IF: 3.08) Cit ISI: 27 Cit Scopus 29
29)Mainiero, F., Colombara, M., Antonini V., Strippoli, R., Merola, M., Poffe,O., Tridente, G., and Ramarli, D. (2003) p38 MAPK is a critical regulator of the constitutive and the beta4 integrin-regulated expression of IL-6 in human normal thymic epithelial cells. European Journal of Immunology. 33, 3038-3048 (IF: 4.84) Cit ISI: 24 Cit Scopus 26
30)Gismondi, A., Jacobelli, J., Strippoli, R., Mainiero, F., Soriani, A., Piccoli, M., Frati, L., Santoni, A. (2003) Pyk-2 integrates chemokine and integrin receptor signalling to control NK transendothelial migration. Journal of Immunology. 170, 3065-3073 (IF: 7.09)
31) D'Auria FD, Tecca M, Strippoli R, Simonetti N In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains. Lett Appl Microbiol. 2001 Apr;32(4):220-3. (IF: 1.189)
32) Mainiero F, Gismondi A, Strippoli R, Jacobelli J, Soriani A, Morrone S, Santoni A Integrin-mediated regulation of cytokine and chemokine production by human natural killer cells.. Eur Cytokine Netw. 2000 Sep;11(3):493-4. (IF: 1.621)
33) Mainiero, F., Gismondi, A., Strippoli, R., Soriani A, Jacobelli, J., Santoni, A. Integrine e cellule Natural Killer (NK) [Integrins and Natural Killer (NK) cells] EOS Rivista di Immunologia ed Immunofarmacologia Volume 20, Issue 3, 2000, Pages 71-76
34)Mainiero, F., Soriani, A., Strippoli, R., Jacobelli, J., Gismondi, A., Piccoli, M., Frati, L. and Santoni, A. (2000) RAC1/P38 MAPK signaling pathway controls beta1 integrin-induced interleukin-8 production in human natural killer cells. Immunity. 12, 7-16 (IF: 20.99)

Rome, March 13th, 2019