A5046840844- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Distributed and Parallel Computing Systems
- Biomedical Research and Pathophysiology
- Protist diversity and phylogeny
- Cystic Fibrosis Research Advances
- Fetal and Pediatric Neurological Disorders
- Genetic Syndromes and Imprinting
- Acute Myeloid Leukemia Research
- Parallel Computing and Optimization Techniques
- Hemoglobinopathies and Related Disorders
- Hedgehog Signaling Pathway Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Scientific Computing and Data Management
- Iron Metabolism and Disorders
- Chronic Myeloid Leukemia Treatments
- Advanced Data Storage Technologies
- Chemotherapy-induced cardiotoxicity and mitigation
- Surgical Simulation and Training
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Retinal Development and Disorders
- Anatomy and Medical Technology
- Hematological disorders and diagnostics
- Chronic Lymphocytic Leukemia Research
Newcastle University
2017-2023
Centre for Life
2018-2023
University of Newcastle Australia
2020
Ospedale San Paolo
2019
Ospedale Policlinico San Martino
2013-2016
University of Milan
2015
Istituto Nazionale di Fisica Nucleare, Sezione di Milano
2008-2011
Istituto Nazionale di Fisica Nucleare, Sezione di Pisa
2006
University of Pisa
2006
IRCCS Istituto Auxologico Italiano
2005
Joubert syndrome (JBTS) is a genetically heterogeneous autosomal-recessive neurodevelopmental ciliopathy. We investigated further the underlying genetic etiology of by studying two unrelated families in whom JBTS was not associated with pathogenic variants known JBTS-associated genes. Combined autozygosity mapping both highlighted candidate locus on chromosome 10 (chr10: 101569997–109106128, UCSC Genome Browser hg 19), and exome sequencing revealed missense ARL3 within locus. The encoded...
The gLite Workload Management System (WMS) is a collection of components that provide the service responsible for distributing and managing tasks across computing storage resources available on Grid. WMS basically receives requests job execution from client, finds required appropriate resources, then dispatches follows jobs until completion, handling failure whenever possible. Other than single batch-like jobs, compound types handled by are Directed Acyclic Graphs (a set where...
Joubert syndrome (JBTS) is the archetypal ciliopathy caused by mutation of genes encoding ciliary proteins leading to multi-system phenotypes, including a cerebello-retinal-renal syndrome. JBTS genetically heterogeneous, however mutations in CEP290 are common underlying cause. The renal manifestation juvenile-onset cystic kidney disease, known as nephronophthisis, typically progressing end-stage failure within first two decades life, thus providing potential window for therapeutic...
Significance The treatment of genetic kidney disease is challenging, as this requires both the correction underlying gene defect and delivery treatment. Here we show that by using antisense oligonucleotides, can induce exon skipping a mutated in CEP290 , within renal epithelial cells derived from patient with ciliopathy syndrome called Joubert syndrome. This rescues truncated protein to near full-length restores ciliary phenotype. In Cep290 murine model syndrome, achievable systemic an...
CEP104 is an evolutionarily conserved centrosomal and ciliary tip protein. loss-of-function mutations are reported in patients with Joubert syndrome, but their function the etiology of ciliopathies poorly understood. Here, we show that cep104 silencing zebrafish causes cilia-related manifestations: shortened cilia Kupffer's vesicle, heart laterality, cranial nerve development defects. We another syndrome-associated protein, CSPP1, interacts at microtubules for regulation axoneme length....
Mutations in CEP290 (also known as NPHP6), a large multidomain coiled coil protein, are associated with multiple cilia-associated syndromes. Over 130 mutations have been linked to wide spectrum of human ciliopathies, raising the question how single gene cause different disease In zebrafish, expressivity cep290 deficiencies were type genetic ablation: acute morpholino knockdown caused severe cilia-related phenotypes, whereas CRISPR/Cas9 mutant restricted photoreceptor defects. Here, we show...
The majority of multi-exon genes undergo alternative splicing to produce different mRNA transcripts and this may occur in a tissue-specific manner. Assessment isolated from blood samples sometimes be unhelpful determining the affect on function putative splice-site variants affecting kidney-specific transcripts. Here we present data demonstrating power using human urine-derived renal epithelial cells (hUREC) as source kidney RNA. We report clinical molecular genetic three affected cases two...
Significance Our current understanding of genetic disease is often inadequate, largely due to background effects that modify presentation. This particularly challenging for rare diseases lack sufficient numbers patients genome-wide association studies. We show in a series experiments using murine model Joubert syndrome, multisystem ciliopathy, single locus modifier cystic kidney disease. go on the human homolog plays similar role cohort patients. These findings make significant contribution...
Half of patients with a ciliopathy syndrome remain unsolved after initial analysis whole exome sequencing (WES) data, highlighting the need for improved variant filtering and annotation. By candidate gene curation WES combined homozygosity mapping, we detected homozygous predicted synonymous allele in NPHP3 two children hepatorenal fibrocystic disease from consanguineous family. Analyses on patient-derived RNA shows activation cryptic mid-exon splice donor leading to frameshift. Remarkably,...
Abstract Joubert syndrome (JBTS) is an incurable multisystem ciliopathy syndrome. The most commonly mutated gene in JBTS patients with a cerebello-retinal-renal phenotype CEP290 (alias JBTS5 ). encoded protein localises to the proximal end of primary cilium, transition zone, where it controls ciliary composition and signalling. We examined cilium structure fibroblast cells derived from homozygous compound heterozygous nonsense mutations show that elongation cilia, impaired ciliogenesis...
The objective of this study was to develop a software application that is able support plastic surgeons interested in applying simulations and soft tissue modeling during presurgical planning activities. By using our user-friendly interface force-displacement graphs, users can analyze scalp skin behaviors when subjected stress. Users 1) determine the dynamic general point after specific force, 2) predict force needed for displacement point, 3) deformation all points entire based on applied....
There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical insights. Autosomal recessive polycystic kidney disease (ARPKD) one leading causes liver-associated morbidity mortality Oman. We describe profile cohort ARPKD patients.We studied patients with diagnosis (n = 40) relatives (parents 24) unaffected siblings 10)) from 32 apparently unrelated families, who were referred to National Genetic Centre Oman between January 2015 December...
Abstract Background PKHD1 is the main genetic cause of autosomal recessive polycystic kidney disease (ARPKD), a hereditary hepato-renal fibrocystic disorder which most important end-stage renal during early childhood. ARPKD can also present in adulthood with milder phenotypes. In this study, we describe 24-year-old woman atypical kidney, no family history and obvious extra-renal manifestations who was referred for investigation. Methods We used combination next generation sequencing, Sanger...
Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It widely used in combination with polychemotherapy regimens for treatment of hematological disorders. There no evidence direct cardiotoxicity drug but few cases cardiovascular adverse events have been reported literature. We report on two patients affected by stage IV non-Hodgkin lymphoma bone marrow infiltration and peripheral blood involvement who experienced accidents temporally related to...
Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It widely used in combination with polychemotherapy regimens for treatment of hematological disorders. There no evidence direct cardiotoxicity drug but few cases cardiovascular adverse events have been reported literature. We report on two patients affected by stage IV non-Hodgkin lymphoma bone marrow infiltration and peripheral blood involvement who experienced accidents temporally related to...
Abstract Kidney disease is one of the leading causes morbidity worldwide, emphasizing importance for physiologically accurate models. With most approved renal drugs failing to perform as well in human clinical trials they did animal testing, it imperative that new and improved human-based models are developed test these potential therapeutics. One option use patient derived cell lines, grown both two-dimensional (2D) three-dimensional (3D) structures, known spheroids organoids. Despite their...
The p63 transcription factor, homolog to the p53 tumor suppressor gene, plays a crucial role in epidermal and limb development, as its mutations are associated human congenital syndromes characterized by skin, craniofacial defects. While skin-specific transcriptional targets being discovered, little is known of post-translation modifications controlling ΔNp63α functions. Here we show that p300 acetyl-transferase physically interacts vivo with catalyzes acetylation on lysine 193 (K193)...
Mutations in ciliary genes cause a spectrum of both overlapping and distinct clinical syndromes (ciliopathies). CEP120 CC2D2A are paradigmatic examples for this genetic heterogeneity pleiotropy as mutations Joubert syndrome but also associated with skeletal ciliopathies Meckel syndrome, respectively. The molecular basis phenotypical variability is not understood basal exon skipping likely contributes to tolerance deleterious via tissue-specific preservation the amount expressed functional...