Siena

Research Activities

The Unit carries out activities in the oncology field pursuing different research themes:

1. Molecular mechanisms that regulate cell growth and transformation, mediated by mitogen-activated protein kinases (MAPK).

2. Role of autophagy in cancer.

3. Use of multifunctional nanoparticles for innovative theranostic approaches to human tumors and development of drug-delivery systems for the targeted delivery of drugs and contrast agents.

4. Development of experimental models for pre-clinical studies of diseases with high social impact.

Scientific Articles

• Leonardi M, Perna E, Tronnolone S, Colecchia D, Chiariello M (2019). Activated kinases screening identifies the IKBKE oncogene as a positive regulator of autophagy. Autophagy. In press. doi: 10.1080/15548627.2018.1517855.

• Iralde-Lorente L, Cau Y, Clementi L, Franci L, Tassone G, Valensin D, Mori M, Angelucci A, Chiariello M, Botta M (2019). Chemically stable inhibitors of 14-3-3 protein-protein interactions derived from BV02. J. Enzyme Inhib. Med. Chem. 34: 657. doi: 10.1080/14756366.2019.1574779.

• Lubrano S, Laura Comelli, Piccirilli C, Marranci A, Dapporto F, Tantillo E, Gemignani F, Gutkind JS, Salvetti A, Chiorino G, Cozza G, Chiariello M, Galli A, Poliseno L, Cervelli T (2019). Development of a yeast-based system to identify new hBRAFV600E functional interactors. Oncogene. 38: 1355. PMID: 30237439; doi: 10.1038/s41388-018-0496-5.

• Colecchia D, Dapporto F, Tronnolone S, Salvini L, Chiariello M (2018). MAPK15 is part of the ULK complex and controls its activity to regulate early phases of the autophagic process. J. Biol. Chem. In press. PMID: 30131341; doi: 10.1074/jbc.RA118.002527.

• Bertuzzi G, Crotti S, Calandro P, Bonini BF, Monaco I, Locatelli E, Fochi M, Zani P, Strocchi E, Mazzanti A, Chiariello M, Comes Franchini M. Quinone‐fused pyrazoles through regio‐selective 1,3‐dipolar cycloadditions: synthesis of tricyclic scaffolds and in vitro cytotoxic activity evaluation on glioblastoma cancer cells (2018). ChemMedChem. doi: 10.1002/cmdc.201800251.

• Calandro P, Iovenitti G, Mancini A, Zamperini C, Candita F, Dreassi E, Chiariello M, Schenone S, Botta M (2018). Plasmin-binding tripeptide-decorated liposomes loading pyrazolo[3,4-d]pyrimidines for the targeting to hepatocellular carcinoma. ACS Medicinal Chemistry Letters. 9: 646. PMID: 30034594; doi: 10.1021/acsmedchemlett.8b00062.

• Grifantini R, Taranta M, Gherardini L, Naldi I, Parri M, Grandi A, Giannetti A, Tombelli S, Lucarini G, Ricotti L, Campagnoli S, De Camilli E, Pelosi G, Baldini F, Menciassi A, Viale G, Pileri P, Cinti C (2018). Magnetically driven drug delivery systems improving targeted immunotherapy for colon-rectal cancer. J Control Release. 280:76. doi: 10.1016/j.jconrel.2018.04.052

• Pietrobono S, Santini R, Gagliardi S, Dapporto F, Colecchia D, Chiariello M, Leone C, Valoti M, Manetti F, Petricci E, Taddei M, Stecca B (2018). Targeted inhibition of Hedgehog-GLI signaling by novel acylguanidine derivatives inhibits melanoma cell growth by inducing replication stress and mitotic catastrophe. Cell Death & Disease. 9: 142. doi: 10.1038/s41419-017-0142-0.

• Colecchia D, Stasi M, Leonardi M, Manganelli F, Nolano M, Veneziani BM, Santoro L, Eskelinen E-L, Chiariello M*, Bucci C* (2017). Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B. Autophagy. PMID: 29130394; doi: 10.1080/15548627.2017.1388475. *Co-corresponding authors.

• Gennaro M, Mattiello A, Mazziotti R, Antonelli C, Gherardini L, Guzzetta A, Berardi N, Cioni G, Pizzorusso T (2017). Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System. Front Neural Circuits. 11: 47. doi: 10.3389/fncir.2017.00047

• Colecchia D, Nicolato E, Ravagli C, Faraoni P, Strambi A, Rossi M, Doumett S, Mosconi E, Locatelli E, Comes Franchini M, Balzi M, Baldi G, Marzola P, Chiariello M. (2017). EGFR-targeted magnetic nanovectors recognize, in vivo, head and neck squamous cells carcinoma-derived tumors. ACS Medicinal Chemistry Letters. 8: 1230-1235. doi: 10.1021/acsmedchemlett.7b00278

• Monaco I, Camorani S, David Colecchia D, Locatelli E, Calandro P, Oudin A, Niclou S, Arra C, Chiariello M*, Cerchia L*, Comes Franchini M* (2017). Aptamer functionalization of nanosystems for Glioblastoma targeting through the Blood-Brain-Barrier. Journal of Medicinal Chemistry. 60: 4510-4516. PMID: 28471660; doi: 10.1021/acs.jmedchem.7b00527. *Co-corresponding authors.

• Vignaroli G, Iovenitti G, Zamperini C, Coniglio F, Calandro P, Molinari A, Fallacara AL, Sartucci A, Calgani A, Colecchia D, Mancini A, Festuccia C, Dreassi E, Valoti M, Musumeci F, Chiariello M, Angelucci A, Botta M, Schenone S (2017). Prodrugs of pyrazolo[3,4-d] pyrimidines: from library synthesis to evaluation as potential anticancer agents in an orthotopic glioblastoma model. Journal of Medicinal Chemistry. 60: 6305-6320. PMID: 28650650; DOI: 10.1021/acs.jmedchem.7b00637

• Fallacara AL, Mancini A, Zamperini C, Marianelli S, Chiariello M, Pozzie G, Santoro F, Botta M, Schenone S (2017). Pyrazolo[3,4-d]pyrimidines-loaded human serum albumin (HSA) nanoparticles: preparation, characterization and cytotoxicity evaluation against neuroblastoma cell line. Bioorganic & Medicinal Chemistry Letters. 27: 3196-3200. PMID: 28558969; DOI: 10.1016/j.bmcl.2017.05.015.

• Vitiello M, Tuccoli A, D’Aurizio R, Sarti S, Giannecchini L, Lubrano S, Marranci A, Evangelista M, Peppicelli S, Ippolito C, Barravecchia I, Guzzolino E, Montagnani V, Gowen M, Mercoledi E, Mercatanti A, Comelli L, Gurrieri S, Wu LW, Ope O, Flaherty K, Boland GM, Hammond MR, Kwong L, Chiariello M, Stecca B, Zhang G, Salvetti A, Angeloni D, Pitto L, Calorini L, Chiorino G, Pellegrini M, Herlyn M, Osman I and Poliseno L (2017). Context-dependent miR-204 and miR-211 differentially affect the biological properties of amelanotic and melanotic melanoma cells. Oncotarget. 8: 25395-25417. PMID: 28445987; DOI: 10.18632/oncotarget.15915.

• Botta L, Maccari G, Calandro P, Tiberi M, Brai A, Zamperini C, Canducci F, Chiariello M, Martí-Centelles R, Falomir E, Carda M (2017). One drug for two targets: Biological evaluation of antiretroviral agents endowed with antiproliferative activity. Bioorganic & Medicinal Chemistry Letters. 27: 2502-2505. PMID: 28408224; DOI: 10.1016/j.bmcl.2017.03.097.

• Musumeci F, Fallacara AL, Brullo C, Grossi G, Botta L, Calandro P, Chiariello M, Kissova M, Crespan E, Maga G and Schenone S (2017). Identification of new pyrrolo[2,3-d]pyrimidines as Src tyrosine kinase inhibitors in vitro active against Glioblastoma. European Journal of Medicinal Chemistry. 127: 369-378. PMID: 28076826; DOI: 10.1016/j.ejmech.2016.12.036.

• Rossi M, Colecchia D, Ilardi G, Acunzo M, Nigita G, Sasdelli F, Celetti A, Strambi A, Staibano S, Croce CM and Chiariello M (2016). MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors. Oncotarget. 7: 20981-98. PMID: 26988910; DOI: 10.18632/oncotarget.8044.

• Bertuzzi G, Locatelli E, Colecchia D, Calandro P, Bonini BF, Chandanshive JZ, Mazzanti A, Zani P, Chiariello M and Comes Franchini M (2016). Straightforward synthesis of a novel ring-fused pyrazole-lactam and in vitro cytotoxic activity on cancer cell lines. European Journal of Medicinal Chemistry. 117: 1-7. PMID: 27081742; DOI: 10.1016/j.ejmech.2016.04.006.

• Vignaroli G, Calandro P, Zamperini C, Coniglio F, GIovenitti G, Tavanti M, Colecchia D, Dreassi E, Valoti M, Schenone S, Chiariello M and Botta M (2016). Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery. Scientific Reports. 6: 21509. PMID: 26898318; DOI: 10.1038/srep21509.

• Bellelli R, Federico G, Mattè A, Colecchia D, Iolascon A, Chiariello M, Santoro M, De Franceschi L and Carlomagno F (2016). NCOA4 deficiency impairs systemic iron homeostasis. Cell Reports. 14, 1–11. PMID: 26776506; DOI: 10.1016/j.celrep.2015.12.065.

• Klionsky DJ, et al. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12: 1-222. PMID: 26799652; DOI: 10.1080/15548627.2015.1100356.

• Valensin D, Cau Y, Calandro P, Vignaroli G, Dello Iacono L, Chiariello M, Mori M and Botta M (2016). Molecular insights to the bioactive form of BV02, a reference inhibitor of 14-3-3σ protein–protein interactions. Bioorg. Med. Chem. Lett. 26: 894-898. PMID: 26774582; DOI: 10.1016/j.bmcl.2015.12.066.

• De Simone M, Panetta D, Bramanti E, Giordano C, Salvatici MC, Gherardini L, Menciassi A, Burchielli S, Cinti C, Salvadori PA (2016). Magnetically driven nanoparticles: 18 FDG-radiolabelling and positron emission tomography biodistribution study. Contrast Media Mol Imaging. 11: 561. doi: 10.1002/cmmi.1718.

• Gherardini L, Sharma A, Capobianco E, Cinti C (2016). Targeting Cancer with Epi-Drugs: A Precision Medicine Perspective. Curr Pharm Biotechnol. 17: 856. PMID: 27229488

• Colecchia D, Rossi M, Sasdelli F, Sanzone S, Strambi A and Chiariello M (2015). MAPK15 mediates BCR-ABL-induced autophagy and regulates oncogene-dependent cell proliferation and tumor formation. Autophagy. 11: 1790-1802. PMID: 26291129; DOI: 10.1080/15548627.2015.1084454.

• Camorani S, Crescenzi E, Colecchia D, Carpentieri A, Amoresano A, Fedele M, Chiariello M and Cerchia L (2015). Aptamer targeting EGFRvIII mutant hampers its constitutive autophosphorylation and affects migration, invasion and proliferation of glioblastoma cells. Oncotarget. 6: 37570-37587. PMID: 26461476; DOI: 10.18632/oncotarget.6066.

• Morra F, Luise C, Merolla F, Poser I, Visconti R, Ilardi G, Paladino S, Inuzuka H, Guggino G, Monaco R, Colecchia D, Monaco G, Cerrato A, Chiariello M, Claudio PP, Staibano S and Celetti A (2015). FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC. Oncotarget. 20: 12697-709. PMID: 25885523; DOI: 10.18632/oncotarget.3708.

• Naddaka M, Locatelli E, Colecchia D, Sambri L, Monaco I, Baschieri A, Sasdelli F, Chiariello M, Matteucci E, Zani P and Comes Franchini M (2015). Hybrid Cholesterol-based nanocarriers containing phosphorescent Ir complexes. In vitro imaging on glioblastoma cell line. RSC Adv. 5: 1091-1096. DOI: 10.1039/c4ra12936a

• Gherardini L, Gennaro M, Pizzorusso T (2015). Perilesional treatment with chondroitinase ABC and motor training promote functional recovery after stroke in rats. Cereb Cortex. 25: 202. doi: 10.1093/cercor/bht217.

• Carlomagno F and Chiariello M (2014). Growth factor transduction pathways: paradigm of anti-neoplastic targeted therapy. J. Mol. Med. 92: 723-733. PMID: 24906458; DOI: 10.1007/s00109-014-1177-7.

• Locatelli E, Matteini P, Sasdelli F, Pucci A, Chiariello M, Molinari V, Pini R and Comes Franchini M. (2014). Surface chemistry and entrapment of magnesium nanoparticles into polymeric micelles: a highly biocompatible tool for photothermal therapy. Chem. Commun. 50: 7783-7786 PMID: 24901445; DOI: 10.1039/c4cc01513d.

• Mori M, Vignaroli G, Cau Y, Dinić J, Hill R, Rossi M, Colecchia D, Pešić M, Link W, Chiariello M, Ottmann C and Botta M (2014). Discovery of 14-3-3 protein-protein interaction inhibitors that sensitize multidrug resistant cancer cells to Doxorubicin and the Akt inhibitor GSK690693. ChemMedChem. 9: 973-983. PMID: 24715717; DOI: 10.1002/cmdc.201400044.

• Naldi I, Taranta M, Gherardini L, Pelosi G, Viglione F, Grimaldi S, Pani L, Cinti C (2014). Novel epigenetic target therapy for prostate cancer: a preclinical study. PLoS One. 9: e98101. doi: 10.1371/journal.pone.0098101.

• Gherardini L, Ciuti G, Tognarelli S, Cinti C (2014). Searching for the perfect wave: the effect of radiofrequency electromagnetic fields on cells. Int J Mol Sci. 15: 5366. doi: 10.3390/ijms15045366.

• Gherardini L, Bardi G, Gennaro M, Pizzorusso T (2014). Novel siRNA delivery strategy: a new "strand" in CNS translational medicine? Cell Mol Life Sci. 71: 1. doi: 10.1007/s00018-013-1310-8.

• Acunzo M, Romano G, Palmieri D, Laganá A, Garofalo M, Balatti V, Drusco A, Chiariello M, Nana-Sinkam P and Croce CM (2013). The cross-talk between MET and EGFR in Non Small Cell Lung Cancer involves miR-27a and Sprouty2. Proc. Natl. Acad. Sci. USA. 110: 8573-8578. PMID: 23650389; DOI: 10.1073/pnas.1302107110.

• Strambi A, Mori M, Rossi M, Colecchia D, Manetti F, Carlomagno F, Botta M and Chiariello M (2013). Structure prediction and validation of the ERK8 kinase domain. PLoS ONE 8(1): e52011. PMID: 23326322; DOI: 10.1371/journal.pone.0052011.

• Colecchia D, Strambi A, Sanzone S, Iavarone C, Rossi M, Dall'armi C, Piccioni F, Verrotti di Pianella A and Chiariello M (2012). MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. Autophagy. 8: 1724-1740. PMID: 22948227; DOI: 10.4161/auto.21857.

• 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 (2012). miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene. 31: 634-642. PMID: 21706050; DOI: 10.1038/onc.2011.260.

• Rossi M, Colecchia D, Iavarone C, Strambi A, Piccioni F, Verrotti di Pianella A and Chiariello M (2011). Extracellular signal-regulated kinase 8 (Erk8) controls estrogen-related receptor α (ERRα) cellular localization and inhibits its transcriptional activity. J. Biol. Chem. 286: 8507-8522. PMID: 21190936; DOI: 10.1074/jbc.M110.179523.

• Chiariello M, Vaqué JP, Crespo P, Gutkind JS (2010). Activation of Ras and Rho GTPases and MAP Kinases by G-protein-coupled receptors. Methods Mol Biol. 661: 137-50.

Staff

How to reach us

Via Fiorentina 1, 
53100 Siena

By bus
Bus Station: opposite Santa Maria Novella Railway Station
‘rapida bus’ (1h 15 mins)
‘diretta bus’ (1h 35 mins)
Autolinee TRA.IN spa (phone: +39 0577 204245)
Autolinee SITA (freephone: 800 373760, phone: +39 055 47821)

From Rome:
Bus Station: Roma Tiburtina railway station (2h 45m)
Autolinee SENA (freephone: 800 930960,
phone: + 39 0577 283203)

By train
From Florence: direct line or change at Empoli (1h30’)
From Rome: change at Chiusi (3h)
From Pisa: change at Empoli (2h)
The railway station in Siena is about 1 km from TLS Foundation.


By car
From the North:
Motorway A1, exit "Firenze Certosa"
Dual carriageway Firenze/Siena, exit "Siena Nord" (40 mins)

From the South:
Motorway A1 exit "Valdichiana"
Bettolle-Siena link road, exit "Siena Nord" (1h 30 mins)
By plane
From Florence:
"Amerigo Vespucci" Airport (70 km)
Shuttle bus to S. Maria Novella railway station every 45 mins
Car rental at airport

From Pisa:
"Galileo Galilei" Airport (150 km)
Car rental at airport

Siena Taxi: +39 0577 49222
Firenze Taxi: +39 055 4390 - 4242
Pisa Taxi: +39 050 41252"