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Università della Svizzera italiana

A novel prostate cell type-specific gene signature to interrogate prostate tumor differentiation status and monitor therapeutic response (running title: Phenotypic classification of prostate tumors)

Mapelli, Sarah N. ; Albino, Domenico ; Mello-Grand, Maurizia ; Shinde, Dheeraj ; Scimeca, Manuel ; Bonfiglio, Rita ; Bonanno, Elena ; Chiorino, Giovanna ; Garcia-Escudero, Ramon ; Catapano, Carlo V. ; Carbone, Giuseppina M.

In: Cancers, 2020, vol. 12, no. 1, p. 23 p

In this study, we extracted prostate cell-specific gene sets (metagenes) to define the epithelial differentiation status of prostate cancers and, using a deconvolution-based strategy, interrogated thousands of primary and metastatic tumors in public gene profiling datasets. We identified a subgroup of primary prostate tumors with low luminal epithelial enrichment (LumElow). LumElow tumors were...

Università della Svizzera italiana

Virus-like particles and nanoparticles for vaccine development against HCMV

Perotti, Michela ; Perez, Laurent

In: Viruses, 2020, vol. 12, no. 1, p. 17 p

Human cytomegalovirus (HCMV) infects more than 70% of the human population worldwide. HCMV is responsible for high morbidity and mortality in immunocompromised patients and remains the leading viral cause of congenital birth defects. Despite considerable efforts in vaccine and therapeutic development, HCMV infection still represents an unmet clinical need and a life-threatening disease in...

Public access from Feb 20, 2020
Università della Svizzera italiana

DNA (hydroxy)methylation in T helper lymphocytes

Monticelli, Silvia

In: Trends in biochemical sciences, 2019, vol. 44, no. 7, p. 589-598

Upon recognition of an antigen, the differentiation of antigen-inexperienced naïve T lymphocytes into subsets able to effectively coordinate host defense is controlled by a network of transcription factors and regulatory molecules. In the cell nucleus, these factors act in the context of epigenetic modifications that influence DNA accessibility and ultimately gene expression. This review...

Public access from May 14, 2020
Università della Svizzera italiana

Proteasomal and lysosomal clearance of faulty secretory proteins : ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways

Fregno, Ilaria ; Molinari, Maurizio

In: Critical reviews in biochemistry and molecular biology, 2019, vol. 54, no. 2, p. 153-163

About 40% of the eukaryotic cell’s proteins are inserted co- or post-translationally in the endoplasmic reticulum (ER), where they attain the native structure under the assistance of resident molecular chaperones and folding enzymes. Subsequently, these proteins are secreted from cells or are transported to their sites of function at the plasma membrane or in organelles of the secretory and ...

Università della Svizzera italiana

Structural basis for broad HIV-1 neutralization by the MPER-specific human broadly neutralizing antibody LN01

Pinto, Dora ; Fenwick, Craig ; Caillat, Christophe ; Silacci, Chiara ; Guseva, Serafima ; Dehez, François ; Chipot, Christophe ; Barbieri, Sonia ; Minola, Andrea ; Jarrossay, David ; Tomaras, Georgia D. ; Shen, Xiaoying ; Riva, Agostino ; Tarkowski, Maciej ; Schwartz, Olivier ; Bruel, Timothée ; Dufloo, Jérémy ; Seaman, Michael S. ; Montefiori, David C. ; Lanzavecchia, Antonio ; Corti, Davide ; Pantaleo, Giuseppe ; Weissenhorn, Winfried

In: Cell host & microbe, 2019, vol. 26, no. 5, p. p. 623-637.e8

Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived...

Università della Svizzera italiana

ESCRT-III-driven piecemeal micro-ER-phagy remodels the ER during recovery from ER stress

Loi, Marisa ; Raimondi, Andrea ; Morone, Diego ; Molinari, Maurizio

In: Nature communications, 2019, vol. 10, p. 5058

The endoplasmic reticulum (ER) produces about 40% of the nucleated cell’s proteome. ER size and content in molecular chaperones increase upon physiologic and pathologic stresses on activation of unfolded protein responses (UPR). On stress resolution, the mammalian ER is remodeled to pre-stress, physiologic size and function on activation of the LC3-binding activity of the translocon...

Università della Svizzera italiana

SHP-2 in lymphocytes’ cytokine and inhibitory receptor signaling

Niogret, Charlène ; Birchmeier, Walter ; Guarda, Greta

In: Frontiers in immunology, 2019, vol. 10, no. 2468, p. 1-11

Somewhat counterintuitively, the tyrosine phosphatase SHP-2 (SH2 domain- containing protein tyrosine phosphatase-2) is crucial for the activation of extracellular signal-regulated kinase (ERK) downstream of various growth factor receptors, thereby exerting essential developmental functions. This phosphatase also deploys proto-oncogenic functions and specific inhibitors have recently been ...

Université de Fribourg

Multilayered control of protein turnover by torc1 and atg1

Hu, Zehan ; Raucci, Serena ; Jaquenoud, Malika ; Hatakeyama, Riko ; Stumpe, Michael ; Rohr, Rudolf ; Reggiori, Fulvio ; Virgilio, Claudio De ; Dengjel, Jörn

In: Cell Reports, 2019, vol. 28, no. 13, p. 3486-3496.e6

The target of rapamycin complex 1 (TORC1) is a master regulator of cell homeostasis, which promotes anabolic reactions and synchronously inhibits catabolic processes such as autophagy-mediated protein degradation. Its prime autophagy target is Atg13, a subunit of the Atg1 kinase complex that acts as the gatekeeper of canonical autophagy. To study whether the activities of TORC1 and Atg1 are...

Università della Svizzera italiana

Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

Sastry, Mallika ; Zhang, Baoshan ; Chen, Man ; Joyce, M. Gordon ; Kong, Wing-Pui ; Chuang, Gwo-Yu ; Ko, Kiyoon ; Kumar, Azad ; Silacci, Chiara ; Thom, Michelle ; Salazar, Andres M. ; Corti, Davide ; Lanzavecchia, Antonio ; Taylor, Geraldine ; Mascola, John R. ; Graham, Barney S. ; Kwong, Peter D.

In: Plos one, 2017, vol. 12, no. 10, p. e0186854

Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer...

Università della Svizzera italiana

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy : IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission

Mele, Federico ; Fornara, Chiara ; Jarrossay, David ; Furione, Milena ; Arossa, Alessia ; Spinillo, Arsenio ; Lanzavecchia, Antonio ; Gerna, Giuseppe ; Sallusto, Federica ; Lilleri, Daniele

In: Plos one, 2017, vol. 12, no. 11, p. e0187731

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve...