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Università della Svizzera italiana

The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer

Yasinska, Inna M. ; Sakhnevych, Svetlana S. ; Pavlova, Ludmila ; Hansen Selnø, Anette Teo ; Teuscher Abeleira, Ana Maria ; Benlaouer, Ouafa ; Gonçalves Silva, Isabel ; Mosimann, Marianne ; Varani, Luca ; Bardelli, Marco ; Hussain, Rohanah ; Siligardi, Giuliano ; Cholewa, Dietmar ; Berger, Steffen M. ; Gibbs, Bernhard F. ; Ushkaryov, Yuri A. ; Fasler-Kan, Elizaveta ; Klenova, Elena ; Sumbayev, Vadim V.

In: Frontiers in immunology, 2019, vol. 10, p. 1594

Human cancer cells operate a variety of effective molecular and signaling mechanisms which allow them to escape host immune surveillance and thus progress the disease. We have recently reported that the immune receptor Tim-3 and its natural ligand galectin-9 are involved in the immune escape of human acute myeloid leukemia (AML) cells. These cells use the neuronal receptor latrophilin 1...

Università della Svizzera italiana

Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

Venereau, Emilie ; Casalgrandi, Maura ; Schiraldi, Milena ; Antoine, Daniel J. ; Cattaneo, Angela ; De Marchis, Francesco ; Liu, Jaron ; Antonelli, Antonella ; Preti, Alessandro ; Raeli, Lorenzo ; Samadi Shams, Sara ; Yang, Huan ; Varani, Luca ; Andersson, Ulf ; Tracey, Kevin J. ; Bachi, Angela ; Uguccioni, Mariagrazia ; Bianchi, Marco E.

In: The journal of experimental medicine, 2012, vol. 209, no. 9, p. 1519-1528

Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to...

Università della Svizzera italiana

Rational engineering of a human anti-dengue antibody through experimentally validated computational docking

Simonelli, Luca ; Pedotti, Mattia ; Beltramello, Martina ; Livoti, Elsa ; Calzolai, Luigi ; Sallusto, Federica ; Lanzavecchia, Antonio ; Varani, Luca

In: Plos one, 2013, vol. 8, no. 2, p. e55561

Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and ...

Università della Svizzera italiana

HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4

Schiraldi, Milena ; Raucci, Angela ; Martínez Muñoz, Laura ; Livoti, Elsa ; Celona, Barbara ; Venereau, Emilie ; Apuzzo, Tiziana ; De Marchis, Francesco ; Pedotti, Mattia ; Bachi, Angela ; Thelen, Marcus ; Varani, Luca ; Mellado, Mario ; Proudfoot, Amanda ; Bianchi, Marco Emilio ; Uguccioni, Mariagrazia

In: The journal of experimental medicine, 2012, vol. 209, no. 3, p. 551-563

After tissue damage, inflammatory cells infiltrate the tissue and release proinflammatory cytokines. HMGB1 (high mobility group box 1), a nuclear protein released by necrotic and severely stressed cells, promotes cytokine release via its interaction with the TLR4 (Toll-like receptor 4) receptor and cell migration via an unknown mechanism. We show that HMGB1- induced recruitment of inflammatory...

Università della Svizzera italiana

Computational docking of antibody-antigen complexes, opportunities and pitfalls illustrated by influenza hemagglutinin

Pedotti, Mattia ; Simonelli, Luca ; Livoti, Elsa ; Varani, Luca

In: International journal of molecular sciences, 2011, vol. 12, no. 1, p. 226-251

Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting...

Università della Svizzera italiana

Rationally modified estrogen receptor protein as a bio-recognition element for the detection of EDC pollutants : strategies and opportunities

Pedotti, Mattia ; Ferrero, Valentina Elisabetta Viviana ; Lettieri, Teresa ; Colpo, Pascal ; Follonier, Stephane ; Calzolai, Luigi ; Varani, Luca

In: International journal of environmental research and public health, 2015, vol. 12, no. 3, p. 2612-2621

The estrogen receptor protein (ER) can bind a vast number of organic pollutants widely spread in the environment and collectively known as Endocrine Disrupting Chemicals, EDCs. Its broad selectivity makes it an ideal bio-recognition element for the detection of EDCs. Here we describe the strategy and rationale for the design of ER based biosensors and assays that generate a signal in the...

Università della Svizzera italiana

Antibody binding modulates conformational exchange in domain III of dengue virus E protein

Moraes, Adolfo H. ; Simonelli, Luca ; Pedotti, Mattia ; Almeida, Fabio C.L. ; Varani, Luca ; Valente, Ana P.

In: Journal of virology, 2016, vol. 90, no. 4, p. 1802-1811

Domain III of dengue virus E protein (DIII) participates in the recognition of cell receptors and in structural rearrangements required for membrane fusion and ultimately viral infection; furthermore, it contains epitopes for neutralizing antibodies and has been considered a potential vaccination agent. In this work, we addressed various structural aspects of DIII and their relevance for both...

Università della Svizzera italiana

Differential expression and biochemical activity of the immune receptor Tim-3 in healthy and malignant human myeloid cells

Gonçalves Silva, Isabel ; Gibbs, Bernhard F. ; Bardelli, Marco ; Varani, Luca ; Sumbayev, Vadim V.

In: Oncotarget, 2015, vol. 6, no. 32, p. 33823-33833

The T cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane-associated receptor which is involved in a variety of biological responses in human immune cells. It is highly expressed in most acute myeloid leukaemia (AML) cells and therefore may serve as a possible target for AML therapy. However, its biochemical activities in primary human AML cells remain unclear. We therefore...

Università della Svizzera italiana

The tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells

Gonçalves Silva, Isabel ; Yasinska, Inna M. ; Sakhnevych, Svetlana S. ; Fiedler, Walter ; Wellbrock, Jasmin ; Bardelli, Marco ; Varani, Luca ; Hussain, Rohanah ; Siligardi, Giulio ; Ceccone, Giacomo ; Berger, Steffen M. ; Ushkaryov, Yuri A. ; Gibbs, Bernhard F. ; Fasler-Kan, Elizaveta ; Sumbayev, Vadim V.

In: Ebiomedicine, 2017, vol. 22, p. 44-57

Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased...

Università della Svizzera italiana

Rational modification of estrogen receptor by combination of computational and experimental analysis

Ferrero, Valentina Elisabetta Viviana ; Pedotti, Mattia ; Chiadò, Alessandro ; Simonelli, Luca ; Calzolai, Luigi ; Varani, Luca ; Lettieri, Teresa

In: Plos one, 2014, vol. 9, no. 7, p. e102658

In this manuscript, we modulate the binding properties of estrogen receptor protein by rationally modifying the amino acid composition of its ligand binding domain. By combining sequence alignment and structural analysis of known estrogen receptor- ligand complexes with computational analysis, we were able to predict estrogen receptor mutants with altered binding properties. These predictions...