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Erika CIONE - Professori Associati

Erika CIONE

Professori Associati

Biochimica (BIOS-07/A)

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BIOGRAPHICAL SKETCH Name Erika Cione Date and Place of Birth March 31st 1974, Cosenza, Italy Nationality Italian Address Via Impennuti – 87040 Luzzi (CS) - Italy Mobile phone (+39) 349 120 51 22 Home phone (+39-0984) 54 19 07 e-mail address erika.cione@unical.it PREVIOUS POSITIONS, APPOINTMENTS & EDUCATIONAL TRAINING 1999 April: Degree in Pharmacy (5 years), University of Calabria Italy 1999 May-2004 October: Post-graduated studies in Clinical Pathology (5 years PhD degree). University of Calabria Italy 2000 September: Visiting Researcher at Dr J.A. Olson Research Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, USA 2005 April: Post Doc in Biochemistry, at University of Calabria Italy 2005 September - 2006 March: Assistant Specialist at Dr JL Napoli’s lab Department of Nutritional Sciences and Toxicology, UC-Berkeley USA 2006 August - 2006 December: Assistant Specialist at Dr JL Napoli’s lab Department of Nutritional Sciences and Toxicology, UC-Berkeley USA 2007 November: Scientific coordinator Tirocinio di Ricerca UNICAL-University of California Berkeley- Regione Calabria POR CALABRIA 2000-2006 - Misura 3.7 Grant for exchange program with Dept. of Nutritional Sciences & Toxicology UC-Berkeley 2008 April: Assistant Professor (permanent position) in Biochemistry University of Calabria Italy 2008 May: Socrates exchange teaching program Jagellonian University Kracow-POLAND. 2008 October-2008 November: Visiting Research at Dr Dr M. Przybylski’s lab Department of Analytical Chemistry and Biopolymer Structure Analysis University of Konstanz-Germany 2009 January-June: Assistant Specialist at Dr JL Napoli’s lab Department of Nutritional Sciences and Toxicology, UC-Berkeley USA 2009 June: Editorial Board Member of American Journal of Pathology 2010 October: Socrates exchange teaching program IGBMC-France Strasbourg University 2011 April: Visiting Professor Kane’s lab University of Baltimore-Maryland-USA 2011 May: Visiting Professor Lisanti’s lab Thomas Jefferson University Philadelphia-USA 2011 September: Socrates exchange teaching program IGBMC-France Strasbourg University 2011 September: Scientific coordinator POR Calabria FSE 2007/2013 Obiettivo Operativo M2 “Sostenere la realizzazione di percorsi individuali di alta formazione per giovani laureati e ricercatori presso organismi di riconosciuto prestigio nazionale e internazionale. Grant for exchange program with Dept. of Pharmaceutical Sciences-University of Maryland-Baltimore CURRENT RESEARCH INTERESTS Retinoic Acid (RA) is the main active metabolite of vitamin A and it is essential to a wide range of physiological processes, including development, nervous system function, immune response, cell proliferation, cell differentiation, and reproduction. Two families of nuclear receptors for RA isomers exist, the Retinoic Acid Receptors (RAR ) and the Retinoid X Receptors (RXR ) . Both of them are ligand-dependent activators of genes transcription. The all-trans isomer activates RARs while the 9-cis one (9cRA) activates both RARs and RXRs in vitro. Both compounds exhibit chemotherapeutic and chemopreventive activities in a number of malignancies, including breast cancer. However, RA therapy is confounded by a marked toxicity of this agent at pharmacological doses and by development of RA-resistance. Central to my work is the use of physiological concentration of RA isomers, to study RA behaviour in leydig tumoral cell lines, where a leukaemia related post-translational modification, termed retinoylation occurs at higher levels than the normal counterparts, as well as in breast cancer. In the latter extent combination of PPAR-ligand rosiglitazone (BRL) and 9-cis RA as RXRs inducer, exerts antiproliferative effects. The compounds were used under pharmacological concentration the first and physiological concentration (50nM) the second. The active collaboration with Dr. M.A. Kane (Dept. of Pharmaceutical Sciences-University of Maryland-Baltimore) about the alteration of retinoid homeostasis in breast cancer is based on the use of a sensitive and robust LC/MS/MS method to quantify individual RA isomers that Dr. Kane herself has developed in the last 5 years. It provides information about retinoids level in normal and tumoral tissues. Indeed, knowledge on the physio/pathological concentration of retinoids in breast cancer is necessary to understand which levels of RA and which of its isomers actively contribute to tumor growth and/or tumor arrest both in the tumor mass as well as in its microenvironment. There is an ongoing study, in collaboration with Dr. M.L. Lisanti (Kimmel Cancer Center-Thomas Jefferson University-Philadelphia) where fibroblasts, of the tumor microenvironment, that lose Caveolin-1 expression are associated with a 4 fold up-regulation of cellular retinoic acid binding protein II. This protein has a major role in shuttling RA to the correct/proper nuclear receptor, mediating either proliferation or growth arrest of breast cancer cells. Recently, my team contributed actively to the first quantification of endogenous levels of 9cRA. In a strict collaboration with Prof J.L. Napoli (Dept. of Nutritional Sciences and Toxicology-University of California-Berkeley), where I was Assistant Specialist for one year. 9cRA was specifically detected in pancreas, more precisely in beta cells, with implication in glucose homeostasis and insulin secretion. The process of glucose stimulated insulin secretion (GSIS), is not completely understood despite a century of study, and the role of 9cRA in beta cell mediated events is still far to be completely ruled out. In beta-cell 9cRA, acts in opposition to glucose to arrest GSIS and possesses both rapid (non-genomic) and long-term (regulating transcription) actions that play key roles in insulin production and secretion. Abnormal increases in pancreas 9cRA accompany diseases characterized by glucose intolerance, such as diet-induced obesity and diabetes. At this point of the study it cannot be excluded that 9cRA homeostasis might be deregulated in impaired GSIS and/or in insulin-resistant diabetes. Such observations highlight the importance of deciphering the mechanism of action of 9cRA in the process of insulin secretion. In the context of this novel and original topic with a highly promising therapeutic impact, a collaboration with Dr. Rochette-Egly C. IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) Illkirch, France, begun in 2010. Dr. Rochette-Egly has an international scientific reputation on RARs and RXRs, their post-translational modification (phosphorylation) as well as the cross-talks with other signaling pathways. In particular we are currently investigating the role of RARs and RXRs in the 832/13 beta cell model of Glucose Stimulated Insulin Secretion and the regulation provided by the pancreas specific autacoid 9cRA. The final important focus of my studies are the roles of nuclear receptors and their accessory proteins in cancer development and diabetes. SCIENTIFIC PUBLICATIONS IF total IF total 93.054 1) Attilio Pingitore, Valentina Carito, Erika Cione*, Ida Perrotta, Domenico Mancuso, Antonio Russo, Giuseppe Genchi, Mariacristina Caroleo * “Localization of nerve growth factor (ngf) receptors in the mitochondrial compartment: characterization and putative role” Biochim Biophys Acta 1820(2) 2012. IF 4.663 *corresponding author 2) Maureen A Kane , Alexandra E Folias , Attilio Pingitore , Mariarita Perri , Chalres R Krois , Joo Yeon Ryu , Erika Cione and Joseph L Napoli, “CrbpI modulates glucose homeostasis and pancreas 9-cis-retinoic acid concentrations” Molecular and Cellular Biology 2011 31(16). IF 6.188 3) Bonofiglio D. , Cione E. , Vizza D. , Perri M. , Pingitore A. , Qi H. , Catalano S. , Rovito D. , Genchi G. , Ando' S. , " Bid as a potential target of apoptotic effects exerted by low doses of PPARg and RXR ligands in breast cancer cells". Cell Cycle, 10(14) 2011. IF 4.999 4) MA Kane, AE Folias, A Pingitore, M Perri, CR Krois, K Obrochta, E Cione, JY Ryu and JL Napoli “Identification of 9-cis-Retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion” Proc Natl Acad Sci 107(50) 2010. IF 9.771 5) M. Perri, A. Pingitore , E. Cione, E. Vilardi, V. Perrone, G.Genchi, " Proliferative and anti-proliferative effects of endogenous levels of retinoic acid in Leydig MLTC-1/R2C/TM-3 cells". Biochim Biophys Acta 9:993-1001 2010. IF 4.663 6) V. Senatore, E. Cione, A. Gnoni, G. Genchi" Retynoilation reactions are inversely related to the cardiolipin levels in rat testes mitochondria from hypothyroid rats". J Bioenerg Biomembr. 4:321-8 2010. IF 4.015 7) Cione E. , Pingitore A. , Genchi F. , Genchi G. , " Coenzyme A enhances activity of the mitochondrial adenine nucleotide translocator". The international journal of biochemistry and cell biology 42:106-12, 2010. IF 4.956 8) Trombino S. , Cassano R. , Ferrarelli T. , Cilea A. , Muzzalupo R. , Cione E. , Picci N. , " Synthesis and antioxidant activity evaluation of novel broom and cotton fibers derivatives". Journal of Applied Polymer Science, 114:3177-83 2009. IF 1.203 9) Trombino S. , Cassano R. , Muzzalupo R. , Pingitore A. , Cione E. , Picci N. , " Stearyl ferulate-based solid lipid nanoparticles for the encapsulation and stabilizzation of beta-carotene and alfa-tocopherol". Colloids and Surfaces B: Biointerfaces, 72:181-87 2009. IF 2.600 10) Pingitore A. , Cione E. , Senatore V. , Genchi G. , " Adrenal glands and testes as steroidogenic tissue are affected by retinoylation reaction.". J Bioenerg Biomembr, 41:215-21 2009. IF 4.015 11) Bonofiglio D. , Cione E. , Qi H. , Pingitore A. , Perri M. , Catalano S. , Vizza D. , Panno M. L. , Genchi G. , Fuqua S. , Ando' S. , " Combined low doses of PPARg and RXR ligands trigger intrinsic apoptotic pathway in human breast cancer cells". The American Journal of Pathology, NuovaSerie, 2009, 175, 1270-1280. IF 5.224 12) Cione E, Pingitore A, Perri M, Genchi G. Influence of all-trans-retinoic acid on oxoglutarate carrier via retinoylation reaction. Biochim Biophys Acta. 791(1):3-7 2009 IF 5.084 13) Tucci P, Cione E, Perri M, Genchi G. All-trans-retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzyme regulation. J Bioenerg Biomembr. 40(4):315-23 2008 IF 4.015 14) Tucci P, Cione E, Genchi G. Retinoic acid-induced testosterone production and retinoylation reaction are concomitant and exhibit a positive correlation in Leydig (TM-3) cells. J Bioenerg Biomembr. 2008 Apr;40(2):111-5. IF 4.015 15) Cione E, Tucci P, Senatore V, Perri M, Trombino S, Iemma F, Picci N, Genchi G. Synthesized esters of ferulic acid induce release of cytochrome c from rat testes mitochondria. J Bioenerg Biomembr. 2008 Feb;40(1):19-26 IF 4.015 16) Cione E, Senatore V, Tucci P, Giudetti AM, Genchi F, Gnoni GV, Genchi G. Dietary fatty acid composition differently influences retinoylation reaction in rat testes mitochondria. J Bioenerg Biomembr. 2007 Apr;39(2):203-9. IF 4.015 17) Ragno G, Risoli A, Ioele G, Cione E, De Luca M. Photostabilization of 1,4-dihydropyridine antihypertensives by incorporation into beta-cyclodextrin and liposomes. J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2979-85. IF 1.44 18) Cione E, Tucci P, Senatore V, Ioele G, Genchi G. Binding of all-trans-retinoic acid to MLTC-1 proteins. Mol Cell Biochem. 2005 Aug;276(1-2):55-60. IF 1.896 19) Cione E, Tucci P, Chimento A, Pezzi V, Genchi G. Retinoylation reaction of proteins in Leydig (TM-3) cells. J Bioenerg Biomembr. 2005 Feb;37(1):43-8. IF 4.015 20) Ioele G, Cione E, Risoli A, Genchi G, Ragno G. Accelerated photostability study of tretinoin and isotretinoin in liposome formulations. Int J Pharm. 2005 Apr 11;293(1-2):251-60. IF 2.962 21) Cione E, Genchi G. Characterization of rat testes mitochondrial retinoylating system and its partial purification. J Bioenerg Biomembr. 2004 Apr;36(2):211-7. IF 4.015 22) Ragno G, Cione E, Garofalo A, Genchi G, Ioele G, Risoli A, Spagnoletta A.Design and monitoring of photostability systems for amlodipine dosage forms. Int J Pharm. 2003 Oct 20;265(1-2):125-32. IF 2.962 PROCEEDINGS 1)E. Cione, D. Bonofiglio, M. Perri, A. Pingitore, D. Vizza, S. Catalano, G. Genchi and S. Andò “Bid as a potential target of apoptotic effects exerted by low doses of PPARγ and RXR ligands in breast cancer cells” EMBO Retinoids Workshop Strasbourg-IGBMC (France) September 22nd 24th 2011 2)E. Cione, A. Pingitore, V. Carito, M. Perri, A. Cordò, A. Greco, N. Liu, MC Caroleo “9cis Retinoic Acid induce translocation of p75 NGF receptor on mitochondria influencing carriers activity” EMBO Retinoids Workshop Strasbourg-IGBMC (France) September 22nd 24th 2011 3)Pingitore A., Perri M., Cione E., Kane MA. “Altered retinoid metabolism in breast cancer ” ASIP Annual meeting at experimental biology – Washington DC USA April 9th-13th 2011. 4)Kane M.A. , Folias A.E. , Pingitore A. , Perri M. , Krois C., Ryu J.Y. , Obrochta K.M. , Cione E. , Napoli J.L. , “CrbpI and retinoid homeostasis” Contributo a FASEB Summer Research Conferences - Retinoids, Carefree - Arizona (USA), 13-18 June 2010. 5)Napoli J., Kane M.A., Pingitore A., Folias A., Perri M., Ryu J.R. Cione E. “The function of retinoids in energy balance”. FASEB Summer Research Conferences – Retinoids – Carefree (AZ) June 13-18 2010. 6)Bonofiglio D. , Cione E. , Vizza D. , Perri M. , Pingitore A. , Qi H. , Catalano S., Panno M.L. , Genchi G., Andò S., “Mitochondrial p53/Bid interaction plays a pro-apoptotic role in response to PPARγ and RXR ligands in breast cancer cells.” ASIP Annual meeting at experimental biology – Anaheim (CA) April 24th-28th 2010. 7)M. Perri, E. Cione, A. Pingitore and G.Genchi, " Proliferative and anti-proliferative effects of endogenous levels of retinoic acid in Leydig MLTC-1/R2C/TM-3 cells". FASEB Retinoids Conference, Carefree 13-18 June 2010. (Oral Comunication) 8)Pingitore A. , Cione E. , Perri M. , Vilardi E. , Genchi G. , " Retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzymes regulation." Atti del convegno "XII Workshop on Apoptosis in Biology and Medicine.”", Parghelia, Vibo Valentia, Calabria, 20th-22nd May 2009. 9)Vilardi E. , Perri M. , Pingitore A. , Cione E. , Genchi G. , " High concentration of ferulic acid and its synthesized esters induce release of cytochrome c from tumoral MLTC-1 cell line.". Atti del convegno "XII Workshop on Apoptosis in Biology and Medicine.”", Parghelia, Vibo Valentia, Calabria, 20th-22nd May, 2009. 10)H. Qi, D. Bonofiglio, E. Cione, A. Pingitore, M. Perri, S. Catalano, M.L. Panno, G. Genchi and S. Andò. " Evidence that combined treatment of BRL and 9 cis RA at low doses induces apoptosis in MCF-7 human breast cancer cells”. Annual WORLD CANCER CONGRESS-2008 Shangai, 13-18 Giugno 2008. 11)Pingitore A., Cione E., Perri M., Tucci P., Senatore V. and Genchi G." Influence of all-trans-Retinoic Acid on Oxoglurate Carrier via Retinoylation Reaction”. FASEB Retinoids Conference, New Haven 15-20 Giugno 2008. (Oral Comunication) 12)Cione E., Bonofiglio D., Qi H., Perri M., Pingitore A., Catalano S., Panno M. L., Genchi G., Ando' S., " Activated pathway through which Rosiglitazone and 9 cis Retinoic Acid, when combined at low doses, induce apoptosis in human breast cancer cells”. FASEB Retinoids Conference, New Haven 15-20 Giugno 2008. (Oral Comunication) 13)M.L. Panno, F. Giordano, V. Rago, V. Bartella, M.G. Palma, D. Bonofiglio, F. De Amicis, E. Cione, S.Ando’ “ Evidences that Bergapten is an Antitumoral Agent that Enhances p53 Gene Expression Indipendendly of its Photoactivation. Congresso ASIP Cosenza, 22-23 Settembre 2008. 14)D. Bonofiglio, E. Cione, H. Qi, A. Pingitore, M. Perri, S. Catalano, M.L. Panno, G. Genchi and S. Andò " The apoptotic effects of both rosiglitazone and 9-cis-retinoic acid at low dose on human breast carcinoma cells as markers of benefit in neoadjuvant therapy of mammary cancer”. Congresso ASIP Cosenza, 22-23 Settembre 2008. 15)Pingitore A. , Bonofiglio D. , Qi H. , Cione E. , Perri M. , Panno M. L. , Genchi G. , Ando' S. , " Novel therapeutic approach: 9 cis RA, a Rexinoid X Receptor ligand, potentiates antiproliferative and apoptotic responses to Peroxisome Proliferator-Activated Receptor ligands in MCF7 human breast cancer cells.". Contributo a IV° Convegno Fondazione Lilli Funaro Ricerca Scientifica e Sviluppo Tecnologico: nuove speranze in oncologia, Cosenza, 22-23 Febbraio 2008. 16)Perri M. , Trombino S. , Pingitore A. , Cione E. , Genchi G. , " Ferulic Acid and its synthesized esters induce release of cytochrome c from tumoral MLTC-1 cell line.". Contributo a IV° Convegno Fondazione Lilli Funaro Ricerca Scientifica e Sviluppo Tecnologico: nuove speranze in oncologia, Cosenza, 22-23 Febbraio 2008. 17)Senatore V. , Cione E. , Tucci P. , Pingitore A. , Perri M. , Gnoni G. V. , Genchi G. , " Retinoylation reaction in hypothyroid rat testes mitochondria". Atti del convegno "In 52° Congresso Nazionale SIB”", Riccione, 2007, 2007, Vol. 56, pp. 145-145. 18)Tucci P. , Cione E. , Senatore V. , Perri M. , Pingitore A. , Genchi G. , " Retinoic acid (RA) induces free radical generation and modulates enzymes antioxidant activity in Leydig (TM-3) cells". Atti del convegno "In 52° Congresso Nazionale SIB", Riccione, 2007, 2007, Vol. 56, pp. 89-89. 19)Tucci P. , Cione E. , Senatore V. , Genchi G. , " Release of cytochrome c is required for Leydig (TM-3) cells apoptosis induced by all-trans-retinoic acid (RA)". Atti del convegno ൻ° Congresso Nazionale SIB", Riccione, 2006, 2006, Vol. 55, pp. 163 20)Tucci P. , Cione E. , Senatore V. , Genchi G. , " All-trans-retinoic acid (RA) induces apoptosis in Leydig (TM-3) cells.". Contributo a “IX Workshop on Apoptosis in Biology and Medicine: Neuroinflammation in neuronal death and repair”., Parghelia (VV), 13-16, Settembre 2006. 21)Senatore V. , Cione E. , Tucci P. , Genchi G. , " Localization of retinoylating system of rat testes mitochondria and cardiolipin effect on retinoylation reaction". Atti del convegno ൻ° Congresso Nazionale SIB", Riccione, 2006, 2006, Vol. 55, pp. 116 22)Tucci P. , Cione E. , Senatore V. , Genchi G. , " Incorporation of retinoic acid into proteins of tumoral leydig (MLTC-1) cells". Atti del convegno ൺ° Congresso Nazionale SIB", Riccione, 2005, 2005, Vol. 54, pp. 50. 23)Tucci P. , Senatore V. , Trombino S. , Cione E. , Genchi G. , " Ferulic acid: antioxidant effect and release of cytochrome c in rat liver mitochondria". Contributo a VIII Workshop on Apoptosis in Biology and Medicine: Plasticity in pain and death, Parghelia (VV), 25-26 maggio 2005. 24)Senatore V. , Cione E. , Tucci P. , Genchi G. , " Retinoylation reaction of rat testes mitochondria in the presence of different inhibitors of carriers and respiratory chain and Krebs cycle substrates". Atti del convegno ൺ° Congresso Nazionale SIB", Riccione, 2005 Vol. 54, pp. 129.
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