A5018408097- Immune Response and Inflammation
- Burkholderia infections and melioidosis
- Cancer-related gene regulation
- Biomedical Research and Pathophysiology
- Chemokine receptors and signaling
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Advanced Glycation End Products research
- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory mediators and NSAID effects
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Asthma and respiratory diseases
- Cancer-related Molecular Pathways
- Brucella: diagnosis, epidemiology, treatment
- RNA Research and Splicing
- Radioactive Decay and Measurement Techniques
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Adrenal Hormones and Disorders
- Supramolecular Chemistry and Complexes
University of Parma
2025
IRCCS Ospedale San Raffaele
2018-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2023
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016-2023
Vita-Salute San Raffaele University
2016-2023
Mylan (Switzerland)
2019
San Raffaele University of Rome
2014-2015
Dulbecco Telethon Institute
2013
Center for Translational Research in Neuroimaging and Data Science
2013
University of Tartu
2012
Abstract Chemokine heterodimers activate or dampen their cognate receptors during inflammation. The CXCL12 chemokine forms with the fully reduced (fr) alarmin HMGB1 a physiologically relevant heterocomplex (frHMGB1•CXCL12) that synergically promotes inflammatory response elicited by G-protein coupled receptor CXCR4. molecular details of complex formation were still elusive. Here we show an integrated structural approach frHMGB1•CXCL12 is fuzzy heterocomplex. Unlike previous assumptions,...
Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature ADPKD, and inhibition glycolysis using analogs ameliorates aggressive PKD preclinical models. Here, we investigated effects chronic treatment with low doses analog 2-deoxy- d -glucose (2DG) on ADPKD progression orthologous slowly progressive murine models created by inducible...
<title>Abstract</title> Metabolic networks and enzyme-molecule connections are still being elucidated. Here, through systematic analysis of gene loss gain across the eukaryotic tree, mapped onto metabolic networks, we build a coevolutionary framework human metabolism. Using this information, identify unmapped genes in pathways, leading to discovery C11orf54 as long-missing decarboxylase glucuronate/pentose pathway. These findings provide insights into an alternative route for sugar...
Mutations in autoimmune regulator (AIRE) gene cause polyendocrinopathy candidiasis ectodermal dystrophy. AIRE is expressed thymic medullary epithelial cells, where it promotes the expression of peripheral-tissue antigens to mediate deletional tolerance, thereby preventing self-reactivity. contains two plant homeodomains (PHDs) which are sites pathological mutations. AIRE-PHD fingers important for transcriptional activity and presumably play a crucial role formation multimeric protein...
Prions are deadly infectious agents made of PrPSc, a misfolded variant the cellular prion protein (PrPC) which self-propagates by inducing misfolding native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), be resistant to potential drugs, or acquire drug resistance, hampering development effective therapies. We identified Zn(II)-BnPyP, tetracationic porphyrin that binds distinct domains PrPC, eliciting dual anti-prion effect. Zn(II)-BnPyP binding C-terminal pocket...
Peptides seldom retain stable conformations if separated from their native protein structure. In an immunological context, this potentially affects the development of selective peptide-based bioprobes and, a vaccine perspective, poses inherent limits in elicitation cross-reactive antibodies by candidate epitopes. Here, 1,4-disubstituted-1,2,3-triazole-mediated stapling strategy was used to stabilize α-helical fold Pal3 peptidic epitope antigen PalBp (BPSL2765) Burkholderia pseudomallei,...
The isoDGR sequence is an integrin-binding motif that has been successfully employed as a tumor-vasculature-homing molecule or for the targeted delivery of drugs and diagnostic agents to tumors. In this context, we previously demonstrated cyclopeptide 2, product conjugation c(CGisoDGRG) (1) 4-(N-maleimidomethyl)cyclohexane-1-carboxamide, can be used tumor-homing ligand nanodrug neoplastic tissues. Here, combining NMR, computational, biochemical methods, show succinimide ring contained in 2...
High-mobility group box 1 protein (HMGB1) is an ubiquitous nuclear that once released in the extracellular space acts as a Damage Associated Molecular Pattern and promotes inflammation. HMGB1 significantly elevated during Pseudomonas aeruginosa infections has clinical relevance respiratory diseases such Cystic Fibrosis (CF). Salicylates are inhibitors. To address pharmacological inhibition of with small molecules, we explored therapeutic potential pamoic acid (PAM), salicylate limited...
Sp140 is a nuclear leukocyte-specific protein involved in primary biliary cirrhosis and risk factor chronic lymphocytic leukemia. The presence of several chromatin related modules such as plant homeodomain (PHD), bromodomain SAND domain suggests role chromatin-mediated regulation gene expression; however, its real function still elusive. Herein we present the solution structure Sp140-PHD finger investigate epigenetic reader vitro. presents an atypical PHD fold which does not bind to histone...
Abstract Background Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence progression. Because current imaging techniques may fail detect small lesions situ carcinomas, with often relapse after initial diagnosis, thereby requiring frequent follow-up treatments. Results In an attempt obtain a sensitive high-resolution modality for cancer, we have developed photoacoustic approach based on the use PEGylated gold nanorods (GNRs) as contrast agent,...
Sotos syndrome is an overgrowth caused by mutations within the functional domains of NSD1 gene coding for NSD1, a multidomain protein regulating chromatin structure and expression. In particular, PHDVC5HCHNSD1 tandem domain, composed classical (PHDV) atypical (C5HCH) plant homeo-domain (PHD) finger, target several pathological missense-mutations. also crucial NSD1-dependent transcriptional regulation interacts with C2HR domain repressor Nizp1 (C2HRNizp1) in vitro. To get molecular insights...
Human Sp140 protein is a leukocyte-specific member of the speckled (Sp) family (Sp100, Sp110, Sp140, Sp140L), class multi-domain nuclear proteins involved in intrinsic immunity and transcriptional regulation. regulates macrophage program implicated several haematologic malignancies. Little known about structural domains its post-translational modifications. We used mass spectrometry biochemical experiments to investigate endogenous SUMOylation Burkitt's Lymphoma cells sites HEK293T cells,...
Burkholderia pseudomallei is the etiological agent of melioidosis, a severe endemic disease in South-East Asia, causing septicemia and organ failure with high mortality rates. Current treatments diagnostic approaches are largely ineffective. The development new tools vaccines toward effective therapeutic opportunities against B. therefore an urgent priority. In framework multidisciplinary project tackling melioidosis through reverse structural vaccinology, BPSL1050 was identified as...
Over recent years, αvβ6 and αvβ8 Arg-Gly-Asp (RGD) integrins have risen to prominence as interchangeable co-receptors for the cellular entry of herpes simplex virus-1 (HSV-1). In fact, employment subtype-specific integrin-neutralizing antibodies or gene-silencing siRNAs has emerged a valuable strategy impairing HSV infectivity. Here, we shift focus more affordable pharmaceutical approach based on small RGD-containing cyclic pentapeptides. Starting from our recently developed...
Combining 2D STD-NMR, computation, biochemical assays and click-chemistry, we have identified a chromogranin-A derived compound (5) that has high affinity bi-selectivity for αvβ6 αvβ8 integrins is stable in microsomal preparations. 5 suitable nanoparticle functionalization delivery to cancer cells, holding promise diagnostic and/or therapeutic applications.
HMGB1 is a key molecule that both triggers and sustains inflammation following infection or injury, involved in large number of pathologies, including cancer. participates the recruitment inflammatory cells, forming heterocomplex with chemokine CXCL12 (HMGB1·CXCL12), thereby activating G-protein coupled receptor CXCR4. Thus, identification molecules disrupt this can offer novel pharmacological opportunities to treat inflammation-related diseases. To identify new HMGB1·CXCL12 inhibitors we...
Graphical abstractAbstractPHD fingers are small chromatin binding domains, that alone or in tandem work as versatile interaction platforms for diversified activities, ranging from the decoding of modification status histone tails to specific recognition non-histone proteins. They play a crucial role their host protein mutations thereof cause several human malignancies. Thus, PHD starting be considered valuable pharmacological targets. While inhibitors chemical probes activity emerging,...
Abstract Extracellular HMGB1 triggers inflammation following infection or injury, and supports tumorigenesis in inflammation-related malignancies. has several redox states: reduced recruits inflammatory cells to injured tissues forming a heterocomplex with CXCL12 signaling via its receptor CXCR4; disulfide-containing binds TLR4 promotes responses. Here we show that Diflunisal, an aspirin-like nonsteroidal anti-inflammatory drug (NSAID) been clinical use for decades, specifically inhibits...
Mutations in the NPHP1 gene, coding for human nephrocystin-1 (NPHP1), cause autosomal recessive disease nephronophthisis, most common of end-stage renal children and adolescents. The function structure are still poorly characterized. presents a modular well keeping with its role as an adaptor protein: it harbors SH3 domain flanked by two glutamic acid-rich regions conserved C-terminal nephrocystin homology (NHD). Similar to other NPHP protein family members, N-terminus contains putative...
Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role the development of this disease subtype. Through expansion transcriptional activating H3K36me2 and suppression repressive H3K27me3 marks, activates aberrant set genes that contribute to growth, adhesive invasive activities. activity also depends on its non-catalytic domains, which facilitate recruitment chromatin through histone binding. In study, using NMR, ITC molecular dynamics...