1985-1988: Pre-doctoral fellow, Dipartimento di Biologia e Patologia Cellulare e Molecolare

July1985 - October 1985: Summer student, Joslin Diabetes Center, Harvard Medcal School, Boston

July 1988: M.D. Summa cum Laude and Honors for Thesis, Naples Medical School

1989-91: Fellow Centro di Endocrinologia ed Oncologia Sperimentale, C.N.R. & Dipartimento di Biologia e Patologia Cellulare e Molecolare

1990-1993: post-doctoral Fellow Joslin Diabetes Center, Harvard Medical School, Boston, USA

October 1995: Ph.D. in Cellular and Molecular Biology and Pathology

October 1997: officially certified for Endocrinology

July 1995- November 2002: C.N.R. Research Associate, Centro di Endocrinologia ed Oncologia di Napoli, Naples Medical School

November 2002 to date: Associate Professor of General Pathology, University of Naples Federico II, Naples, Italy

Our group focuses on apoptosis in human diseases. We study both molecular mechanisms of drug-induced apoptosis resistance in human cancer and molecular mechanisms of cellular damages caused by an excessive apoptosis. In particular, we studied the role of an anti-apoptotic protein PED and on the serine-threonine kinase AKT. AKT activation causes cellular proliferation and apoptosis resistance. We identified new AKT interactors: PED, Bcl-w and c-FLIP. AKT-mediated PED phosphorylation blocks apoptosis and DISC formation induced by TNFα, TRAIL and FAS-L. Bcl-w is an anti-apoptotic member of Bcl2 family proteins. It is stabilized by AKT and protects cells from drug-induced apoptosis. C-FLIP is an anti-apoptotic protein. We demonstrated that the interaction with AKT mediates the effects on GSK3 beta and TRAIL response of cancer cells.
Recently we focused on microRNAs (miRs) and their involvement in apoptosis resistance for development of innovative tools for cancer diagnosis and therapy. miRs are small endogenous non coding RNAs which negatively regulate mRNA translation. We identified the specific miR that down-regulate PED. We associated miRs-221/222 expression to TRAIL resistance in human non small cell lung cancer, by their specific targeting of p27kip1. In order to better characterize miRs-221/222 role in apoptosis resistance, we identified new miRs-221/222 targets and we are identifying new miRs involved in apoptosis resistance in human glioma. We are also studying the role of miRs in cancer stem cells biology.
Furthermore, we are trying to isolate selective cellular surface markers of cancer stem cells, by the methodology of aptamer-based SELEX.

These projects are in collaboration with Prof. Carlo Maria Croce, Ohio State University, Vittorio de Franciscis, IEOS/CNR, Ruggero De maria, ISS Rome, Giorgio Stassi, Palermo.
Existing grants: AIRC, MERIT-Miur.

1. Garofalo M, Romano G., Quintavalle C., Romano MF, Chiurazzi F, Zanca C, and Condorelli G. (2007) Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cell to TRAIL-induced apoptosis, Int. J. Cancer 120(6):1215-22
2. D'Alessio A., Cerchia L., Amelio I, Incoronato M., Condorelli G., and de Franciscis V. (2007) Shp2 in PC12 cells: NGF versus EGF signalling. Cellular Signalling, 19:1193-1200
3. Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu CG, Croce CM, and Condorelli G. (2008) MicroRNA signatures of TRAIL resistance in human non small cell lung cancer. Oncogene Jun 19;27(27):3845-55.
4. Todaro, M, Lombardo Y, Perez Alea M, Francipale MG, Di Stefano AB, Iovino F, Cammareri P, Agrusta A, Hass TL, Condorelli G, Walczak H, and Stassi G. (2008) Apoptosis resistance in ethithelial tumors is mediated by tumor-cell-derived interleukin-4. Cell Death and Differentiation Cell Death Differ.15(4):762-72.
5. Zanca C, Garofalo M, Quintavalle C, Romano G, Acunzo M, Ragno P.,Montuori N, Incoronato M, Tornillo L, Baumhoer D, Briguori C, Terracciano L, and Condorelli G (2008) PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer J Cell Mol Med. 12(6A):2416-26.
6. Garofalo M, Quintavalle C, Zanca C, de Rienzo A., Romano G, Acunzo M, Puca L, Incoronato M, Croce CM, and Condorelli G. Akt regulates drugs induced cell death through the anti-apoptotic protein Bcl-w (2008), PLoS ONE. 3(12):e4070.
7. Garofalo M, Condorelli G, and Croce M (2008) MicroRNAs in diseases and drug response. Current Opinion in Pharmacology, 8(5):661-7.
8. Obradovic D, Zanca C, Vogl A, Trümbach D, Deussing J, Condorelli G, Rein T. Vitamin D(3) signalling in the brain enhances the function of Phosphoprotein Enriched in Astrocytes-15 KDa (PEA-15). (2009) J Cell Mol Med. 9999, (999A): 2007-13
9. Garofalo M, Condorelli GL, Croce C. and Condorelli G. MicroRNAs as regulators of death receptors signalling (2009) Cell Death and Differentiation, 1–9
10. Insabato l, Amelio I, Quarto M, Zannetti A, Tolino F, de Mauro G, Cerchia L, Riccio P, Baumhoer D, Condorelli G, Terracciano L, de Franciscis V. SHP-1 tyrosine phosphatase defines a subset of high grade breast tumors. Oncology 2010, 77(6):378-84.
11. Garofalo G, Di Leva G, Romano G, Nuovo G, Suh S, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM. MiR-221&222 regulate TRAIL-resistance and enhance tumorigenicity through PTEN and TIMP3 down-regulation. Cancer Cell (2009) Dec 8;16(6):498-509. *Condorelli G and Croce C are co-corresponding authors
12. Incoronato M, Garofalo M, Urso L, Romano G , Quintavalle C, Zanca C, Iaboni M, Nuovo G, Croce CM 5, and Condorelli G miR-212 increases TRAIL sensitivity in non-small cell lung cancer by targeting the anti-apoptotic protein PED (2010) Cancer Res, 70(9):3638-46.
14. Quintavalle C, Incoronato M, Puca L, Acunzo M, Zanca C, Romano G, Garofalo M, Iaboni M, Croce CM, and Condorelli G. (2010) Novel mechanisms of c-FLIPL anti-apoptotic signaling: involvement of Akt-Gsk3 beta pathway. Cell Death and Diff. 17(12):1908-16
15. Zanca C, Cozzolino F, Quintavalle C, Di Costanzo S, Lucia Ricci-Vitiani L, Santoriello M, Monti M, Pucci P, and Condorelli G (2010) J Cell Physiol. Oct;225(1):63-72.
16. Briguori C, Visconti G, Ricciardelli B, Condorelli G. (2011). Renal insufficiency following contrast media administration trial II (REMEDIAL II): RenalGuard system in high-risk patients for contrast-induced acute kidney injury: rationale and design. EuroIntervention 6(9):1117-22
17. Catuogno S, Carla L. Esposito CL, C Quintavalle C, Laura Cerchia L, Condorelli G. and de Franciscis V (2011) Recent Advance in Biosensors for microRNAs Detection in Cancer. Cancer, 3(2), 1877-1898
18. Quintavalle C, Brenca M, De Micco F, Fiore D, Romano S, Romano MF, Apone F, Bianco A, Zabatta MA, Troncone G, Briguori C, Condorelli G. (2011) In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis. Cell death and disease, May 12;2:e155.
19. Quintavalle C, Garofalo M, Zanca C, Romano R, Iaboni M, del Basso De Caro M, J. Carlos Martinez-Montero, Incoronato M, Nuovo G, Croce CM, and Condorelli G. miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ. Oncogene, (2011) in press.
20. Acunzo M, Visone R, Romano G, Veronese A, Lovat F, Palmieri D, Bottoni A, Garofalo M, Gasparini P, Condorelli G., Chiariello M, and Croce CM. miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221&222. Oncogene, (2011) in press.

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