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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
Tel. +41 91 820 0300 - Fax +41 91 820 0302 - info [at] irb [dot] usi [dot] ch

Luca Varani, PhD

Biologia Strutturale

Direttore di laboratorio

Via Vela, 6
6500 Bellinzona, Switzerland

Luca Varani
Bio

Luca Varani si è laureato in chimica all’università di Milano e conseguito un dottorato di ricerca al prestigioso MRC-Laboratory of Molecular Biology (Cambridge, UK), usando biologia molecolare e strutturale per studiare le interazioni RNA-proteina. Ha contribuito a dimostrare il ruolo chiave giocato dal RNA nella regolazione dell’espressione genica e ha mostrato come il RNA stesso possa essere considerato un bersaglio terapeutico contro la demenza. Le numerose pubblicazioni di alto livello, culminate nella determinazione della più grande struttura tridimensionale ottenuta, fino ad allora, tramite la risonanza magnetica, gli hanno permesso di ottenere una posizione a Stanford con una “long term EMBO fellowship”, riservata ai migliori giovani biologi molecolari europei. In California Luca Varani ha completato il primo studio di risonanza magnetica sui complessi TCR/pMHC, che giocano un ruolo chiave nel sistema immunitario.

Dall’ottobre del 2007 guida il gruppo di biologia strutturale dell’Istituto di Ricerca in Biomedicina (IRB) di Bellinzona. L’attività principale riguarda la caratterizzazione delle interazioni tra patogeni ed anticorpi, molecole del sistema immunitario in grado di curare e proteggerci da malattie (per esempio vaccini). Il gruppo cerca di capire quali siano le caratteristiche molecolari che permettono ad un dato anticorpo di eliminare un patogeno. Gli studi si concentrano principalmente su “malattie orfane” come il virus Dengue, Zika, Prione od alcune forme rare di leucemia. L’approccio NMR sviluppato a Stanford è stato spinto avanti all’IRB grazie all’utilizzo di tecniche computazionali che permette di scoprire a quale parte del patogeno si leghi un anticorpo. Informazioni sperimentali guidano e validano le simulazioni al computer e permettono di ottenere una struttura atomica tridimensionale del complesso anticorpo/patogeno. Il gruppo è riuscito a modificare e migliorare un anticorpo esistente aumentandone l’efficacia contro il virus Dengue utilizzando, per la prima volta, solo informazioni computazionali. Hanno anche completato uno dei rari studi NMR su anticorpi, mostrando come l’anticorpo alteri la flessibilita’ dell’antigene.

 Il gruppo si caratterizza per l’approccio fortemente multidisciplinare che svaria dalla determinazione di strutture molecolari agli esperimenti cellulari, dalla biologia computazionale alla produzione e modificazione razionale di proteine ed anticorpi, dalla sintesi di nanoparticelle alla microscopia elettronica.

Progetti
Investigating the role of Interleukin 3 and TIM3 for the detection and elimination of Acute Mieloid Leukemia
RADAR: Rationally Designed Aquatic Receptors for the detection of organic pollutants
Prediction and characterization of antibody-protein interactions in Dengue virus
Characterization of antibody-protein interactions in Diphtheria Toxin
Pubblicazioni
Mapping Antibody Epitopes by Solution NMR Spectroscopy: Practical Considerations
L. Simonelli, M. Pedotti, M. Bardelli, S. Jurt, O. Zerbe, L. Varani
in Methods Mol Biol (2018) vol. 1785 pp29-51
A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein
J. Tan, B. K. Sack, D. Oyen, I. Zenklusen, L. Piccoli, S. Barbieri, M. Foglierini, C. S. Fregni, J. Marcandalli, S. Jongo, S. Abdulla, L. Perez, G. Corradin, L. Varani, F. Sallusto, B. K. L. Sim, S. L. Hoffman, S. H. I. Kappe, C. Daubenberger, I. A. Wilson, A. Lanzavecchia
in Nat Med (2018) vol. 24 pp401-407
Highly specific targeting of human acute myeloid leukaemia cells using pharmacologically active nanoconjugates
I. M. Yasinska, G. Ceccone, I. Ojea-Jimenez, J. Ponti, R. Hussain, G. Siligardi, S. M. Berger, E. Fasler-Kan, M. Bardelli, L. Varani, W. Fiedler, J. Wellbrock, U. Raap, B. F. Gibbs, L. Calzolai, V. V. Sumbayev
in Nanoscale (2018) vol. 10 pp5827-5833
Label-Free Biosensor Detection of Endocrine Disrupting Compounds Using Engineered Estrogen Receptors
R. La Spina, V. E. V. Ferrero, V. Aiello, M. Pedotti, L. Varani, T. Lettieri, L. Calzolai, W. Haasnoot, P. Colpo
in Biosensors (Basel) (2017) vol. 8
A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential
J. Wang, M. Bardelli, D. A. Espinosa, M. Pedotti, T. S. Ng, S. Bianchi, L. Simonelli, E. X. Y. Lim, M. Foglierini, F. Zatta, S. Jaconi, M. Beltramello, E. Cameroni, G. Fibriansah, J. Shi, T. Barca, I. Pagani, A. Rubio, V. Broccoli, E. Vicenzi, V. Graham, S. Pullan, S. Dowall, R. Hewson, S. Jurt, O. Zerbe, K. Stettler, A. Lanzavecchia, F. Sallusto, A. Cavalli, E. Harris, S. M. Lok, L. Varani, D. Corti
in Cell (2017) vol. 171 pp229-241 e15
* J. Wang and M. Bardelli contributed equally ; S-M Lok, L.Varani and D. Corti contributed equally.
The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells
I. Goncalves Silva, I. M. Yasinska, S. S. Sakhnevych, W. Fiedler, J. Wellbrock, M. Bardelli, L. Varani, R. Hussain, G. Siligardi, G. Ceccone, S. M. Berger, Y. A. Ushkaryov, B. F. Gibbs, E. Fasler-Kan, V. V. Sumbayev
in EBioMedicine (2017) pp44-57
Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia
S. Arcangeli, M. C. Rotiroti, M. Bardelli, L. Simonelli, C. F. Magnani, A. Biondi, E. Biagi, S. Tettamanti, L. Varani
in Mol Ther (2017) vol. 25 pp1933-1945
Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery
F. Fumagalli, J. Noack, T. J. Bergmann, E. C. Presmanes, G. B. Pisoni, E. Fasana, I. Fregno, C. Galli, M. Loi, T. Solda, R. D'Antuono, A. Raimondi, M. Jung, A. Melnyk, S. Schorr, A. Schreiber, L. Simonelli, L. Varani, C. Wilson-Zbinden, O. Zerbe, K. Hofmann, M. Peter, M. Quadroni, R. Zimmermann, M. Molinari
in Nat Cell Biol (2016) vol. 18 pp1173-1184
Fumagalli, F. , Noack J. and Bergmann T. contributed equally to this work. * Recommended by the Faculty of 1000
Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection
K. Stettler, M. Beltramello, D. A. Espinosa, V. Graham, A. Cassotta, S. Bianchi, F. Vanzetta, A. Minola, S. Jaconi, F. Mele, M. Foglierini, M. Pedotti, L. Simonelli, S. Dowall, B. Atkinson, E. Percivalle, C. P. Simmons, L. Varani, J. Blum, F. Baldanti, E. Cameroni, R. Hewson, E. Harris, A. Lanzavecchia, F. Sallusto, D. Corti
in Science (2016) vol. 353 pp823-6
K. S and M. B contributed equally to this work; D. A. E. ; V. G. ; A. C. ; S. B. and F. V contributed equally to this work; F. S. and D. C contributed equally to this work and are co-corresponding authors.
The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells
I. Goncalves Silva, L. Ruegg, B. F. Gibbs, M. Bardelli, A. Fruehwirth, L. Varani, S. M. Berger, E. Fasler-Kan, V. V. Sumbayev
in Oncoimmunology (2016) vol. 5 ppe1195535
Interleukin-1 beta induces the expression and production of stem cell factor by epithelial cells: crucial involvement of the PI-3K/mTOR pathway and HIF-1 transcription complex
R. W. Wyszynski, B. F. Gibbs, L. Varani, D. Iannotta, V. V. Sumbayev
in Cell Mol Immunol (2016) vol. 13 pp47-56
Antibody Binding Modulates Conformational Exchange in Domain III of Dengue Virus E Protein
A. H. Moraes, L. Simonelli, M. Pedotti, F. C. Almeida, L. * Varani, A. P. Valente
in J Virol (2015) vol. 90 pp1802-11
* Co-corresponding author
Differential expression and biochemical activity of the immune receptor Tim-3 in healthy and malignant human myeloid cells
I. Goncalves Silva, B. F. Gibbs, M. Bardelli, L. * Varani, V. V. Sumbayev
in Oncotarget (2015) vol. 6 pp33823-33
* Co-corresponding author
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
D. Corti, J. Zhao, M. Pedotti, L. Simonelli, S. Agnihothram, C. Fett, B. Fernandez-Rodriguez, M. Foglierini, G. Agatic, F. Vanzetta, R. Gopal, C. J. Langrish, N. A. Barrett, F. Sallusto, R. S. Baric, L. Varani, M. Zambon, S. Perlman, A. Lanzavecchia
in Proc Natl Acad Sci U S A (2015) vol. 112 pp10473-8
D.C. and J.Z. contributed equally to this work.
Epitope mapping by solution NMR spectroscopy
M. Bardelli, E. Livoti, L. Simonelli, M. Pedotti, A. Moraes, A. P. Valente, L. Varani
in J Mol Recognit (2015) vol. 28 pp393-400
Rationally Modified Estrogen Receptor Protein as a Bio-Recognition Element for the Detection of EDC Pollutants: Strategies and Opportunities
M. Pedotti, V. E. Ferrero, T. Lettieri, P. Colpo, S. Follonier, L. Calzolai, L. Varani
in Int J Environ Res Public Health (2015) vol. 12 pp2612-21
The immune receptor Tim-3 mediates activation of PI3 kinase/mTOR and HIF-1 pathways in human myeloid leukaemia cells
A. Prokhorov, B. F. Gibbs, M. Bardelli, L. Ruegg, E. Fasler-Kan, L. * Varani, V. V. Sumbayev
in Int J Biochem Cell Biol (2014) vol. 59C pp11-20
* Co-last and co-corresponding author
Rational modification of estrogen receptor by combination of computational and experimental analysis
V. E. Ferrero, M. Pedotti, A. Chiadò, L. Simonelli, L. Calzolai, T. Lettieri, L. Varani
in PLoS One (2014) vol. 9 ppe102658
Opening Study on the Development of a New Biosensor for Metal Toxicity Based on Pseudomonas fluorescens Pyoverdine
A. Chiadò, L. Varani, F. Bosco, L. Marmo
in Biosensors in Environmental Studies (2013) vol. 4 pp385-99
Receptor-based high-throughput screening and identification of estrogens in dietary supplements using bioaffinity liquid-chromatography ion mobility mass spectrometry
P. Aqai, N. G. Blesa, H. Major, M. Pedotti, L. Varani, V. E. Ferrero, W. Haasnoot, M. W. Nielen
in Anal Bioanal Chem (2013) vol. 405 pp9427-36
Rational Engineering of a Human Anti-Dengue Antibody through Experimentally Validated Computational Docking
L. Simonelli, M. Pedotti, M. Beltramello, E. Livoti, L. Calzolai, F. Sallusto, A. Lanzavecchia, L. Varani
in PLoS One (2013) vol. 8 ppe55561
Luca Simonelli, Mattia Pedotti contributed equally to this work.
Gold nanoparticles downregulate interleukin-1beta-induced pro-inflammatory responses
V. V. Sumbayev, I. M. Yasinska, C. P. Garcia, D. Gilliland, G. S. Lall, B. F. Gibbs, D. R. Bonsall, L. Varani, F. Rossi, L. Calzolai
in Small (2013) vol. 9 pp472-7
Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release
E. Venereau, M. Casalgrandi, M. Schiraldi, D. J. Antoine, A. Cattaneo, F. De Marchis, J. Liu, A. Antonelli, A. Preti, L. Raeli, S. S. Shams, H. Yang, L. Varani, U. Andersson, K. J. Tracey, A. Bachi, M. Uguccioni, M. E. Bianchi
in J Exp Med (2012) vol. 209 pp1519-28
HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4
M. Schiraldi, A. Raucci, L. M. Munoz, E. Livoti, B. Celona, E. Venereau, T. Apuzzo, F. De Marchis, M. Pedotti, A. Bachi, M. Thelen, L. Varani, M. Mellado, A. Proudfoot, M. E. Bianchi, M. Uguccioni
in J Exp Med (2012) vol. 209 pp551-63
* Highlights, Nat. Rev. Immunol. 2012, 12:232
Computational docking of antibody-antigen complexes, opportunities and pitfalls illustrated by influenza hemagglutinin
M. Pedotti, L. Simonelli, E. Livoti, L. Varani
in Int J Mol Sci (2011) vol. 12 pp226-51
The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity
M. Beltramello, K. L. Williams, C. P. Simmons, A. Macagno, L. Simonelli, N. T. Quyen, S. Sukupolvi-Petty, E. Navarro-Sanchez, P. R. Young, A. M. de Silva, F. A. Rey, L. Varani, S. S. Whitehead, M. S. Diamond, E. Harris, A. Lanzavecchia, F. Sallusto
in Cell Host Microbe (2010) vol. 8 pp271-83
Antonio Lanzavecchia and Federica Sallusto are co-corresponding authors.
Rapid structural characterization of human antibody-antigen complexes through experimentally validated computational docking
L. Simonelli, M. Beltramello, Z. Yudina, A. Macagno, L. Calzolai, L. Varani
in J Mol Biol (2010) vol. 396 pp1491-507
The Diversity of Nuclear Magnetic Resonance Spectroscopy
C. W. Liu, V. Y. Alekseyev, J. R. Allwardt, A. J. Bankovich, B. J. Cade-Menun, R. W. Davis, L. S. Du, K. C. Garcia, D. Herschlag, C. Khosla, D. A. Kraut, Q. Li, B. Null, J. D. Puglisi, P. A. Sigala, J. F. Stebbins, L. Varani
in Biophysics and the Challenges of Emerging Threats (2009) pp65-81
Solution mapping of T cell receptor docking footprints on peptide-MHC
L. Varani, A. J. Bankovich, C. W. Liu, L. A. Colf, L. L. Jones, D. M. Kranz, J. D. Puglisi, K. C. Garcia
in Proc Natl Acad Sci U S A (2007) vol. 104 pp13080-5
Elucidation of the interleukin-15 binding site on its alpha receptor by NMR
N. A. Hanick, M. Rickert, L. Varani, A. J. Bankovich, J. R. Cochran, D. M. Kim, C. D. Surh, K. C. Garcia
in Biochemistry (2007) vol. 46 pp9453-61
Nuclear magnetic resonance methods to study structure and dynamics of RNA-protein complexes
M. Allen, L. Varani, G. Varani
in Methods Enzymol (2001) vol. 339 pp357-76
Nuclear magnetic resonance methods to study RNA-protein complexes
P. Bayer, L. Varani, G. Varani
in Methods Enzymol (2000) vol. 317 pp198-220
A novel mutation at position +12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTD-Kumamoto)
M. Yasuda, J. Takamatsu, I. D'Souza, R. A. Crowther, T. Kawamata, M. Hasegawa, H. Hasegawa, M. G. Spillantini, S. Tanimukai, P. Poorkaj, L. Varani, G. Varani, T. Iwatsubo, M. Goedert, D. G. Schellenberg, C. Tanaka
in Ann Neurol (2000) vol. 47 pp422-9
The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A protein
L. Varani, S. I. Gunderson, I. W. Mattaj, L. E. Kay, D. Neuhaus, G. Varani
in Nat Struct Biol (2000) vol. 7 pp329-35
Structural basis for recognition of the RNA major groove in the tau exon 10 splicing regulatory element by aminoglycoside antibiotics
L. Varani, M. G. Spillantini, M. Goedert, G. Varani
in Nucleic Acids Res (2000) vol. 28 pp710-9
Changes in side-chain and backbone dynamics identify determinants of specificity in RNA recognition by human U1A protein
A. Mittermaier, L. Varani, D. R. Muhandiram, L. E. Kay, G. Varani
in J Mol Biol (1999) vol. 294 pp967-79
Refinement of the structure of protein-RNA complexes by residual dipolar coupling analysis
P. Bayer, L. Varani, G. Varani
in J Biomol NMR (1999) vol. 14 pp149-55
Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17
L. Varani, M. Hasegawa, M. G. Spillantini, M. J. Smith, J. R. Murrell, B. Ghetti, A. Klug, M. Goedert, G. Varani
in Proc Natl Acad Sci U S A (1999) vol. 96 pp8229-34
RNA-protein interactions and protein-protein interactions during regulation of eukaryotic gene expression
L. Varani, A. Ramos, P. Cole, D. Neuhaus, G. Varani
in J Korean Magnetic Resonance Soc (1998) vol. 2 pp152-157
Partially folded structure of monomeric bovine beta-lactoglobulin
H. Molinari, L. Ragona, L. Varani, G. Musco, R. Consonni, L. Zetta, H. L. Monaco
in FEBS Lett (1996) vol. 381 pp237-43