De Francesco Raffaele

Principal Investigator

 

Bio

Raffaele De Francesco earned a degree of Doctor in Biology from the University of Milan. Subsequently, he was a postdoctoral fellow at Emory University, Atlanta, U.S.A., and at the European Molecular Biology Laboratory, Heidelberg, Germany.
Between 1991 and 2008, Raffaele De Francesco worked at I.R.B.M./Merck Research Laboratory in Rome (Italy), where he worked on the identification of molecular targets for antiviral therapy and the development HCV enzyme inhibitors as novel agents for the treatment chronic hepatitis C. As of October 2008, he moved to I.N.G.M.
Raffaele De Francesco is internationally recognized for his pioneering work on many different aspects of the molecular virology of the hepatitis C virus and for his research activity in the field of antiviral drug discovery. He published over 100 research articles in international peer-reviewed journals and several book chapters.
His current research interests cover several aspects of hepatitis C virus biology and pathogenesis, ranging from the identification of viral and host genetic determinants that influence liver disease progression in different individuals, to the role deregulated  lipid metabolism in the pathogenesis of HCV-associated chronic liver disease and liver cancer.

Projects

  • Role of phosphoinositol 4-phosphate metabolism and PI4K kinases in the pathogenesis of chronic liver disease and liver cancer.
  • Regulation of PI4K gene expression by miRNA and/or ceRNA or by long-noncoding transcripts and effect of disregulated gene expression on tumor growth and survival.
  • Identification of host and viral genetic determinants implicated in the progression of hepatic and extra-hepatic diseases associated with chronic hepatitis C (i.e. liver fibrosis, cirrhosis, hepatocarcinoma).
  • Dissection by RNASeq of transcript landscape modifications (both in coding and long non-coding RNAs) induced by interferon treatment in hepatic cell lines.

Recent Publications

Why is it so difficult to develop a hepatitis C virus preventive vaccine?
Zingaretti, C., De Francesco, R., and Abrignani, S.
Clin Microbiol Infect 2014; 20 Suppl 5: 103-109

Oxysterol-binding protein is a phosphatidylinositol 4-kinase effector required for HCV replication membrane integrity and cholesterol trafficking
Wang, H., Perry, J. W., Lauring, A. S., Neddermann, P., De Francesco, R., and Tai, A. W.
Gastroenterology 2014; 146: 1373-1385 e1371-1311

Photodynamic antibacterial and antibiofilm activity of RLP068/Cl against Staphylococcus aureus and Pseudomonas aeruginosa forming biofilms on prosthetic material
Vassena, C., Fenu, S., Giuliani, F., Fantetti, L., Roncucci, G., Simonutti, G., Romano, C. L., De Francesco, R., and Drago, L.
Int J Antimicrob Agents 2014; 44: 47-55

Genome-wide analysis of DNA methylation, copy number variation, and gene expression in monozygotic twins discordant for primary biliary cirrhosis
Selmi, C., Cavaciocchi, F., Lleo, A., Cheroni, C., De Francesco, R., Lombardi, S. A., De Santis, M., Meda, F., Raimondo, M. G., Crotti, C., Folci, M., Zammataro, L., Mayo, M. J., Bach, N., Shimoda, S., Gordon, S. C., Miozzo, M., Invernizzi, P., Podda, M., Scavelli, R., Martin, M. R., Lasalle, J. M., and Gershwin, M. E.
Front Immunol Front Immunol 2014; 5: 128

NS5A inhibitors impair NS5A- PI4KIIIalpha complex formation and cause a decrease of PI4P and cholesterol levels in HCV-associated membranes
Reghellin, V., Donnici, L., Fenu, S., Berno, V., Calabrese, V., Pagani, M., Abrignani, S., Peri, F., De Francesco, R., and Neddermann, P.
Antimicrob Agents Chemother 2014

Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors
McGivern, D. R., Masaki, T., Williford, S., Ingravallo, P., Feng, Z., Lahser, F., Asante-Appiah, E., Neddermann, P., De Francesco, R., Howe, A. Y., and Lemon, S. M.
Gastroenterology 2014; 147: 453-462 e457

In vitro antibiofilm activity of bioactive glass S53P4
Drago, L., Vassena, C., Fenu, S., De Vecchi, E., Signori, V., De Francesco, R., and Romano, C. L.
Future Microbiol 2014; 9: 593-601

Interleukin 28B genotype and insulin resistance in chronic hepatitis C patients
Degasperi, E., Valenti, L., Aghemo, A., De Francesco, R., Rumi, M., Soffredini, R., Donnici, L., Cheroni, C., Fargion, S., Zanoni, V., Orsi, E., and Colombo, M.
Antivir Ther 2014

Interaction between PNPLA3 I148M Variant and Age at Infection in Determining Fibrosis Progression in Chronic Hepatitis C
De Nicola, S., Dongiovanni, P., Aghemo, A., Cheroni, C., D’Ambrosio, R., Pedrazzini, M., Marabita, F., Donnici, L., Maggioni, M., Fargion, S., Colombo, M., De Francesco, R., and Valenti, L.
PLoS One 2014; 9: e106022

The association of IL28B genotype with the histological features of chronic hepatitis C is HCV genotype dependent
D’Ambrosio, R., Aghemo, A., De Francesco, R., Rumi, M. G., Galmozzi, E., De Nicola, S., Cheroni, C., Clark, P. J., Ronchi, G., Lampertico, P., and Colombo, M.
Int J Mol Sci 2014; 15: 7213-7224

Daclatasvir: a team player rather than a prima donna in the treatment of hepatitis C
Aghemo, A., and De Francesco, R.
Gut 2014

Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses
Nizzoli, G., Krietsch, J., Weick, A., Steinfelder, S., Facciotti, F., Gruarin, P., Bianco, A., Steckel, B., Moro, M., Crosti, M., Romagnani, C., Stolzel, K., Torretta, S., Pignataro, L., Scheibenbogen, C., Neddermann, P., De Francesco, R., Abrignani, S., and Geginat, J.
Blood 2013; 122: 932-942

IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B
Lampertico, P., Vigano, M., Cheroni, C., Facchetti, F., Invernizzi, F., Valveri, V., Soffredini, R., Abrignani, S., De Francesco, R., and Colombo, M.
Hepatology 2013; 57: 890-896

Hepatitis C virus-specific directly acting antiviral drugs
Delang, L., Neyts, J., Vliegen, I., Abrignani, S., Neddermann, P., and De Francesco, R.
Curr Top Microbiol Immunol 2013; 369: 289-320

Cirrhosis and rapid virological response to peginterferon plus ribavirin determine treatment outcome in HCV-1 IL28B rs12979860 CC patients
Aghemo, A., Degasperi, E., Rumi, M. G., Galmozzi, E., Valenti, L., De Francesco, R., De Nicola, S., Cheroni, C., Grassi, E., and Colombo, M.
Biomed Res Int 2013; 2013: 580796

New horizons in hepatitis C antiviral therapy with direct-acting antivirals
Aghemo, A., and De Francesco, R.
Hepatology 2013; 58: 428-438

Identification of new autoantigens by protein array indicates a role for IL4 neutralization in autoimmune hepatitis
Zingaretti, C., Arigo, M., Cardaci, A., Moro, M., Crosti, M., Sinisi, A., Sugliano, E., Cheroni, C., Marabita, F., Nogarotto, R., Bonnal, R. J., Marcatili, P., Marconi, M., Zignego, A., Muratori, P., Invernizzi, P., Colombatto, P., Brunetto, M., Bonino, F., De Francesco, R., Geginat, J., Pagani, M., Muratori, L., Abrignani, S., and Bombaci, M.
Mol Cell Proteomics 2012; 11: 1885-1897

Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4
De Nicola, S., Aghemo, A., Grazia Rumi, M., Galmozzi, E., Valenti, L., Soffredini, R., De Francesco, R., Prati, G. M., D’Ambrosio, R., Cheroni, C., Donato, M. F., and Colombo, M.
Hepatology 2012; 55: 336-342

Metabolism of phosphatidylinositol 4-kinase IIIalpha-dependent PI4P Is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity
Bianco, A., Reghellin, V., Donnici, L., Fenu, S., Alvarez, R., Baruffa, C., Peri, F., Pagani, M., Abrignani, S., Neddermann, P., and De Francesco, R.
PLoS Pathog 2012; 8: e1002576

Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b
Rossi, R. L., Rossetti, G., Wenandy, L., Curti, S., Ripamonti, A., Bonnal, R. J., Birolo, R. S., Moro, M., Crosti, M. C., Gruarin, P., Maglie, S., Marabita, F., Mascheroni, D., Parente, V., Comelli, M., Trabucchi, E., De Francesco, R., Geginat, J., Abrignani, S., and Pagani, M.
Nat Immunol 2011; 12: 796-803

Genetic variation in the interleukin-28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection
Marabita, F., Aghemo, A., De Nicola, S., Rumi, M. G., Cheroni, C., Scavelli, R., Crimi, M., Soffredini, R., Abrignani, S., De Francesco, R., and Colombo, M.
Hepatology 2011; 54: 1127-1134

Discovery of (7R)-14-cyclohexyl-7-{[2-(dimethylamino)ethyl](methyl) amino}-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid (MK-3281), a potent and orally bioavailable finger-loop inhibitor of the hepatitis C virus NS5B polymerase.
Narjes F, Crescenzi B, Ferrara M, Habermann J, Colarusso S, Ferreira Mdel R, Stansfield I, Mackay AC, Conte I, Ercolani C, Zaramella S, Palumbi MC, Meuleman P, Leroux-Roels G, Giuliano C, Fiore F, Di Marco S, Baiocco P, Koch U, Migliaccio G, Altamura S, Laufer R, De Francesco R, Rowley M.
J Med Chem. 2011; 54: 289-301

Genetic variation in the interleukin-28B gene is not associated with fibrosis progression in patients with chronic hepatitis C and known date of infection
Marabita, F., Aghemo, A., De Nicola, S., Rumi, M. G., Cheroni, C., Scavelli, R., Crimi, M., Soffredini, R., Abrignani, S., De Francesco, R., and Colombo, M.
Hepatology 2011; 54: 1127-1134

Mechanism of hepatitis C virus RNA polymerase inhibition with dihydroxypyrimidines
Powdrill, M. H., Deval, J., Narjes, F., De Francesco, R., and Gotte, M.
Antimicrob Agents Chemother 2010; 54: 977-983

Vaccination against hepatitis C virus
Abrignani, S., De Francesco, R., and Houghton, M. In New Generation Vaccines (Levine, M. M., Dougan, G., Good, M. F., Liu, M. A., Nabel, G. J., Nataro, J. P., and Rappuoli, R., Eds.) (2010) 4th ed.,
Informa Healthcare, New York.

INGM researches are supported by