A5037015741- Hepatitis C virus research
- Amyotrophic Lateral Sclerosis Research
- Liver Disease Diagnosis and Treatment
- Parkinson's Disease Mechanisms and Treatments
- Hepatitis B Virus Studies
- Neurological diseases and metabolism
- Single-cell and spatial transcriptomics
- Liver Diseases and Immunity
- Neurogenetic and Muscular Disorders Research
- Systemic Lupus Erythematosus Research
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Autism Spectrum Disorder Research
- Epigenetics and DNA Methylation
- Neurobiology and Insect Physiology Research
- interferon and immune responses
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Invertebrate Immune Response Mechanisms
- Genetic Neurodegenerative Diseases
- Bioinformatics and Genomic Networks
- Diabetes and associated disorders
- Cell Image Analysis Techniques
- Genomics and Rare Diseases
Human Technopole
2017-2025
University of Milan
2017-2023
European Institute of Oncology
2017-2022
Istituto Nazionale Genetica Molecolare
2011-2021
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2021
Institute of Molecular Genetics
2017
Mario Negri Institute for Pharmacological Research
2005-2014
University of Campania "Luigi Vanvitelli"
2013
Sapienza University of Rome
2013
University of Naples Federico II
2013
Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)-induced viral clearance in patients chronic hepatitis C. Whether this is also true for the difficult-to-cure B e antigen (HBeAg)-negative (CHB) unknown. One hundred and one HBeAg-negative (92% genotype D) compensated CHB (84% males, 46 years; virus [HBV] DNA: 6.0 log cp/mL; alanine aminotransferase [ALT]: 136 IU/L; 42% cirrhosis) were followed up a median of 11 years (range, 1-17) after 23 months 10-48) either...
In familial and sporadic amyotrophic lateral sclerosis (ALS) in rodent models of the disease, alterations ubiquitin-proteasome system (UPS) may be responsible for accumulation potentially harmful ubiquitinated proteins, leading to motor neuron death. spinal cord transgenic mice expressing ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we found a decrease constitutive proteasome subunits during disease progression, as assessed by real-time PCR immunohistochemistry. parallel,...
ABSTRACT Convergent evidence associates endocrine disrupting chemicals (EDCs) with major, increasingly-prevalent human disorders. Regulation requires elucidation of EDC-triggered molecular events causally linked to adverse health outcomes, but two factors limit their identification. First, experiments frequently use individual chemicals, whereas real life entails simultaneous exposure multiple EDCs. Second, population-based and experimental studies are seldom integrated. This drawback was...
Polymorphisms in the interleukin-28B ( IL28 B) region are associated with spontaneous and treatment-induced viral clearance hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at IL28B locus influences natural history of chronic HCV Thus, we asked an association between polymorphisms liver fibrosis progression existed. We studied 247 consecutive patients HCV, accurate estimate date infection, a biopsy performed before any treatment. No patient had alcohol...
Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that disrupted trajectories with an accelerated and delayed generation of, respectively, inhibitory excitatory neurons yields, at days 60 120, symmetrically opposite...
Abstract Delivering macromolecules across biological barriers such as the blood–brain barrier limits their application in vivo. Previous work has demonstrated that Toxoplasma gondii , a parasite naturally travels from human gut to central nervous system (CNS), can deliver proteins host cells. Here we engineered T. ’s endogenous secretion systems, rhoptries and dense granules, multiple large (>100 kDa) therapeutic into neurons via translational fusions toxofilin GRA16. We demonstrate...
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, protein aggregation has been proposed as possible pathogenetic mechanism. However, the aggregate constituents are poorly characterized so knowledge on role of in pathogenesis limited.We carried out proteomic analysis composition insoluble fraction, model aggregates, from familial ALS (fALS) mouse at different disease stages. We identified several proteins enriched detergent-insoluble fraction already...
Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 too is unknown. The aim was investigate predictive power rs12979860 IL28B SNP Peg-IFN Rbv patients. All consecutively treated between September 2004 June 2010 PegIFN at two liver centers Maggiore...
Activated lymphocytes release nano-sized vesicles (exosomes) containing microRNAs that can be monitored in the bloodstream. We asked whether elicitation of immune responses is followed by lymphocyte-specific microRNAs. found that, upon activation vitro, human and mouse down-modulate intracellular miR-150 accumulate it exosomes. In vivo, levels increased significantly serum humans immunized with flu vaccines mice ovalbumin, this increase correlated elevation antibody titers. Immunization...
Primary biliary cirrhosis (PBC) is an uncommon autoimmune disease with a homogeneous clinical phenotype that reflects incomplete concordance in monozygotic (MZ) twins. We have taken advantage of unique collection consisting genomic DNA and mRNA from peripheral blood cells female MZ twins (n = 3 sets) sisters similar age 8 pairs) discordant for disease. performed genome-wide study to investigate differences (i) methylation (using custom tiled four-plex array containing 50-mers 19,084 randomly...
The regulation of the proliferation and polarity neural progenitors is crucial for development brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator both polarity, yet functional relevance its signaling unique features human corticogenesis remains to be elucidated. We harnessed cortical organoids probe longitudinal impact GSK3 inhibition through multiple developmental stages. Chronic increased caused massive derangement tissue architecture....
Mutations in the Cu,Zn-superoxide dismutase (SOD1) gene cause a familial form of amyotrophic lateral sclerosis (ALS) through an unknown gain-of-function mechanism. Mutant SOD1 aggregation may be toxic property. In fact, proteinaceous inclusions rich mutant have been found tissues from ALS patients and animals, before disease onset. However, very little is known constituents mechanism formation aggregates ALS. We others shown that there progressive accumulation detergent-insoluble spinal cord...
Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome featuring hypersociability, while duplication microduplication (7Dup), frequently exhibiting autism spectrum disorder (ASD). Converging evidence indicates GTF2I as key mediator of the cognitive-behavioral phenotypes, yet its role in cortical development behavioral hallmarks remains largely unknown. We integrated proteomic transcriptomic...
Dissecting human neurobiology at high resolution and with mechanistic precision requires a major leap in scalability, given the need for experimental designs that include multiple individuals and, prospectively, population cohorts. To lay foundation this, we have developed benchmarked complementary strategies to multiplex brain organoids by pooling cells from different pluripotent stem cell (PSC) lines either during organoid generation (mosaic models) or before single-cell RNA sequencing...
Abstract Primordial germ cells (PGCs) are the embryonic precursors of gametes. In mice and rats, PGCs can readily acquire pluripotency in vitro by forming (EGCs). To date, a comparable system has not been established humans, despite fact that human (hPGCs) undergo pluripotent conversion context cell tumorigenesis. Here we report hPGC-like (hPGCLCs) to germ-like (hEGCLCs) upon exposure same inductive signals previously used derive mouse EGCs. This defined, feeder-free culture allows efficient...
There is increasing evidence that endocrine disrupting chemicals (EDCs) are contributing to the rise in metabolic disorders and obesity. Humans constantly exposed numerous EDCs, thus human exposure entails complex EDC mixtures. In this study, we examined effects of an mixture, mixture G, composed four phthalate esters, triclosan, three poly- och perfluorinated alkyl substances. Mixture G had previously been defined based on its association with lower birth weight a pregnancy cohort, where...
Abstract Brain organoids are becoming increasingly relevant to dissect the molecular mechanisms underlying psychiatric and neurological conditions. The in vitro recapitulation of key features human brain development affords unique opportunity investigating developmental antecedents neuropsychiatric conditions context actual patients’ genetic backgrounds. Specifically, multiple strategies organoid (BO) differentiation have enabled investigation cerebral corticogenesis with increasing...
Autoimmune hepatitis (AIH) is an unresolving inflammation of the liver unknown cause. Diagnosis requires exclusion other conditions and presence characteristic features such as specific autoantibodies. Presently, these autoantibodies have relatively low sensitivity specificity are identified via immunostaining cells or tissues; therefore, there a diagnostic need for better easy-to-assess markers. To identify new AIH-specific autoantigens, we developed protein microarray comprising 1626 human...
Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, most patients, the SBDS gene. protein required maturation 60S ribosomes. SDS patients present exocrine pancreatic insufficiency, neutropenia, chronic infections, and skeletal abnormalities. Later life, prone to myelodisplastic syndrome acute myeloid leukemia (AML). It unknown why develop AML which...