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Università della Svizzera italiana

Label-free biosensor detection of endocrine disrupting compounds using engineered estrogen receptors

La Spina, Rita ; Ferrero, Valentina E. V. ; Aiello, Venera ; Pedotti, Mattia ; Varani, Luca ; Lettieri, Teresa ; Calzolai, Luigi ; Haasnoot, Willem ; Colpo, Pascal

In: Biosensors, 2018, vol. 8, no. 1, p. 1-15

Endocrine Disrupting Compounds (EDCs) are chemical substances shown to interfere with endogenous hormones affecting the endocrine, immune and nervous systems of mammals. EDCs are the causative agents of diseases including reproductive disorders and cancers. This highlights the urgency to develop fast and sensitive methods to detect EDCs, which are detrimental even at very low concentrations....

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

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

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

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

Opening study on the development of a new biosensor for metal toxicity based on pseudomonas fluorescens pyoverdine

Chiadò, Alessandro ; Varani, Luca ; Bosco, Francesco ; Marmo, Luca

In: Biosensors, 2013, vol. 3, no. 4, p. 385-399

To date, different kinds of biosensing elements have been used effectively for environmental monitoring. Microbial cells seem to be well-suited for this task: they are cheap, adaptable to variable field conditions and give a measurable response to a broad number of chemicals. Among different pollutants, heavy metals are still a major problem for the environment. A reasonable starting point...

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...

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

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

A bispecific immunotweezer prevents soluble PrP oligomers and abolishes prion toxicity

Bardelli, Marco ; Frontzek, Karl ; Simonelli, Luca ; Hornemann, Simone ; Pedotti, Mattia ; Mazzola, Federica ; Carta, Manfredi ; Eckhardt, Valeria ; D’Antuono, Rocco ; Virgilio, Tommaso ; González, Santiago F. ; Aguzzi, Adriano ; Varani, Luca

In: Plos pathogens, 2018, vol. 14, no. 10, p. e1007335

Antibodies to the prion protein, PrP, represent a promising therapeutic approach against prion diseases but the neurotoxicity of certain anti-PrP antibodies has caused concern. Here we describe scPOM-bi, a bispecific antibody designed to function as a molecular prion tweezer. scPOM-bi combines the complementarity-determining regions of the neurotoxic antibody POM1 and the neuroprotective...