A5016691060- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Genetic Syndromes and Imprinting
- Biomedical Research and Pathophysiology
- Hedgehog Signaling Pathway Studies
- Protist diversity and phylogeny
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- Urological Disorders and Treatments
- Metabolism and Genetic Disorders
- Cerebrospinal fluid and hydrocephalus
- Organ Donation and Transplantation
- Genomic variations and chromosomal abnormalities
- Animal Virus Infections Studies
- Tumors and Oncological Cases
- Viral Infections and Vectors
- Acute Kidney Injury Research
- Neonatal and fetal brain pathology
- Vaccine Coverage and Hesitancy
- Brazilian Legal Issues
- vaccines and immunoinformatics approaches
- Leptospirosis research and findings
- Cellular transport and secretion
- Single-cell and spatial transcriptomics
National Institutes of Health
2014-2023
National Institute of Diabetes and Digestive and Kidney Diseases
2014-2023
Instituto Nacional de Saúde
2023
Ricardo (United Kingdom)
2023
Algarve Biomedical Center
2023
Administracao Central do Sistema de Saude
2023
Universidade do Porto
2022
Johns Hopkins Medicine
2006-2010
Johns Hopkins University
2006-2010
Universidade de São Paulo
2002-2008
Polycystin-1 (PC1) has an essential function in renal tubular morphogenesis and disruption of its causes cystogenesis human autosomal dominant polycystic kidney disease. We have previously shown that recombinant PC1 is cis-autoproteolytically cleaved at the G protein-coupled receptor proteolytic site domain. To investigate role cleavage vivo, we generated by gene targeting a Pkd1 knockin mouse (Pkd1(V/V)) expresses noncleavable PC1. The Pkd1(V/V) mice show hypomorphic phenotype,...
BackgroundThe major gene mutated in autosomal dominant polycystic kidney disease was first identified over 20 years ago, yet its function remains poorly understood. We have used a systems-based approach to examine the effects of acquired loss Pkd1 adult mouse as it transitions from normal cystic state.MethodsWe performed transcriptional profiling large set male and female kidneys, along with metabolomics lipidomics analyses subset kidneys. also assessed modest diet change on cyst progression...
Recent studies have reported intrinsic metabolic reprogramming in Pkd1 knock-out cells, implicating dysregulated cellular metabolism the pathogenesis of polycystic kidney disease. However, exact nature changes and their underlying cause remains controversial. We show herein that k o /ko renal epithelial cells impaired fatty acid utilization, abnormal mitochondrial morphology function, mitochondria kidneys ADPKD patients morphological alterations. further a C-terminal cleavage product...
Polycystic kidney disease (PKD) describes a heterogeneous collection of disorders that differ significantly with respect to their etiology and clinical presentation. They share, however, abnormal tubular morphology as common feature, leading the hypothesis respective gene products may function cooperatively in pathway maintain integrity. To study pathobiology one major form human PKD, we generated mouse line floxed allele Pkhd1 , orthologue mutated autosomal recessive PKD. Cre-mediated...
Mutations at a single locus, PKHD1, are responsible for causing human autosomal recessive polycystic kidney disease (ARPKD). Recent studies suggest that the cystic might result from defects in planar cell polarity, but how 4074 amino acid ciliary protein encoded by longest open reading frame of this transcriptionally complex gene may regulate process is unknown. Using novel vitro expression systems, we show PKHD1 product polyductin/fibrocystin undergoes complicated pattern Notch-like...
Mutations in PKD1 cause the majority of cases autosomal dominant polycystic kidney disease (ADPKD). Because polycystin 1 modulates cell proliferation, differentiation, and apoptosis, its lower biologic activity observed ADPKD might influence degree injury after renal ischemia/reperfusion. We induced ischemia/reperfusion 10- to 12-wk-old male noncystic Pkd1(+/-) wild-type mice. Compared with mice, heterozygous mice had higher fractional excretions sodium potassium serum creatinine 48 h. In...
Background Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of inherited renal failure that results from mutations in PKD1 and PKD2. The disorder characterized by focal cyst formation involves somatic mutation the wild type allele large fraction cysts. Consistent with two-hit mechanism, mice are homozygous for inactivating either Pkd1 or Pkd2 develop cystic kidneys, edema hemorrhage typically die midgestation. Cystic unlikely to be fetal loss since function not required...
Autosomal Dominant Polycystic Kidney Disease (ADPKD; MIM ID's 173900, 601313, 613095) leads to end-stage kidney disease, caused by mutations in PKD1 or PKD2. Inactivation of Pkd1 before after P13 mice results distinct early- late-onset disease. Using a mouse model ADPKD carrying floxed alleles and an inducible Cre recombinase, we intensively analyzed the relationship between renal maturation cyst formation applying transcriptomics metabolomics follow disease progression large number animals...
Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Cby1, the mammalian orthologue of Drosophila Chibby protein, localizes to mature centrioles, is important for ciliogenesis multiciliated airway epithelia mice, antagonizes canonical Wnt signaling via direct regulation β-catenin. We report that deletion mouse Cby1 gene results cystic kidneys, a phenotype common ciliopathies, facilitates formation primary cilia ciliary...
Abstract We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 BA.2 lineages against infection disease progression. During April–June 2022, we implemented a case–case cohort study classified using whole-genome sequencing or spike gene target failure. For the study, adjusted odds ratios (aORs) vaccination logistic regression. VE progression penalized observed no reduced for (aOR 1.07 [95% CI 0.93–1.23]) 0.96 0.84–1.09]) infection. Among...
Abstract Background In a context of multiple Omicron lineages circulation, it is relevant to clarify the effect vaccination and previous infections on risk infection severe post-infection outcomes. Methods Using electronic health records SARS-CoV-2 laboratory surveillance data, we conducted case-case cohort study covering period BA.2/BA.5 lineage replacement in Portugal, compare vaccine effectiveness complete primary booster dose against infection, COVID-19 hospitalization, mortality....
Abstract Autosomal recessive polycystic kidney disease (ARPKD) is an important childhood nephropathy, occurring 1 in 20,000 live births. The major clinical phenotypes are expressed the with dilatation of collecting ducts, systemic hypertension, and progressive renal insufficiency, liver biliary dysgenesis, portal tract fibrosis, hypertension. hypertension has been attributed to enhanced distal sodium reabsorption kidney, structural defects have ascribed altered cellular morphology, fibrosis...