A5070051485- Renal Diseases and Glomerulopathies
- Cell Adhesion Molecules Research
- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Genetic and Kidney Cyst Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Platelet Disorders and Treatments
- Connective tissue disorders research
- Wnt/β-catenin signaling in development and cancer
- Renal cell carcinoma treatment
- Health Systems, Economic Evaluations, Quality of Life
- Genetic Associations and Epidemiology
- Financial Markets and Investment Strategies
- AI in cancer detection
- Genetic factors in colorectal cancer
- Collagen: Extraction and Characterization
- Urological Disorders and Treatments
- Stock Market Forecasting Methods
- Pregnancy and Medication Impact
- Pediatric Urology and Nephrology Studies
- Vasculitis and related conditions
- Monoclonal and Polyclonal Antibodies Research
- Tuberous Sclerosis Complex Research
- Peptidase Inhibition and Analysis
- Renal and Vascular Pathologies
University Health Network
2009-2025
University of Toronto
2003-2025
Toronto General Hospital
2014-2025
Toronto General Hospital Research Institute
2017-2025
Dublin Business School
2024
SickKids Foundation
2021
Wellcome Centre for Cell-Matrix Research
2021
Chittagong University of Engineering & Technology
2020
Pediatric Nephrology of Alabama
2019
Institute of Medical Sciences
2019
Identification of single-gene causes steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding pathogenesis this disease. Here, using a combination homozygosity mapping and whole human exome resequencing, we identified mutations in aarF domain containing kinase 4 (ADCK4) gene 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which been shown participate coenzyme Q10 (CoQ10) biosynthesis. Mutations resulted reduced CoQ10 levels...
Women of childbearing age on conventional hemodialysis (CHD) have decreased fertility when compared with the general population. Even in women who conceived, maternal morbidity and fetal mortality remained elevated. We hypothesized that nocturnal (NHD) (3 to 6 sessions per week, 8 h treatment), by augmenting uremic clearance, leads a more hospitable environment therefore superior outcomes pregnancy CHD.This is descriptive cohort study all female patients achieving delivering live infant...
FSGS is characterized by segmental scarring of the glomerulus and a leading cause kidney failure. Identification genes causing has improved our understanding disease mechanisms points to defects in glomerular epithelial cell, podocyte, as major factor pathogenesis. Using combination genome-wide linkage studies whole-exome sequencing kindred with familial FSGS, we identified missense mutation R431C anillin (ANLN), an F-actin binding cell cycle gene, FSGS. We screened 250 additional families...
Background and objectives FSGS nephrotic syndrome studies have shown that single gene causes are more likely to be found in pediatric cases than adults. Consequently, many examined limited panels largely cohorts. Design, setting, participants, & measurements Whole-exome sequencing was performed adults with diagnosed between 1976 2017 the Toronto GN Registry. An expanded panel of 109 genes linked FSGS, glomerular basement membrane abnormalities, as well ESKD including congenital...
FSGS is characterized by the presence of partial sclerosis some but not all glomeruli. Studies familial have been instrumental in identifying podocytes as critical elements maintaining glomerular function, underlying mutations identified for forms this genetically heterogeneous condition. Here, exome sequencing members an index family with dominant revealed a nonconservative, disease-segregating variant PAX2 transcription factor gene. Sequencing probands cohort seven rare and private...
Mutations of PKD1 and PKD2 account for 85 15% cases autosomal dominant polycystic kidney disease (ADPKD), respectively. Clinically, is more severe than PKD2, with a median age at ESRD 53.4 versus 72.7 yr. In this study, we explored whether family history renal severity predicts the mutated gene in ADPKD. We examined function (estimated GFR ESRD) 484 affected members from 90 families who had ADPKD whose underlying genotype was known. found that presence least one member developed < or =55...
In 1927 Arthur Cecil Alport, a South African physician, described British family with an inherited form of kidney disease that affected males more severely than females and was sometimes associated hearing loss. 1961, the eponymous name Alport syndrome adopted. late twentieth century three genes responsible for were discovered: COL4A3, COL4A4, COL4A5 encoding α3, α4, α5 polypeptide chains type IV collagen, respectively. These assemble to heterotrimers collagen in glomerular basement...
T cell factor (Tcf) proteins bind beta-catenin and are downstream effectors of Wnt/beta-catenin signals. A recently demonstrated interaction between the androgen receptor (AR) ligand binding domain has suggested that AR may be a Tcf-independent effector. This study demonstrates there is direct DNA (DBD) Tcf4. Tcf4 bound specifically to glutathione S-transferase-ARDBD fusion protein could coimmunoprecipitated with transfected or endogenous in prostate cancer cells. Transfected repressed...
Abstract Alport syndrome (AS) is an inherited disorder characterized by kidney disease, sensorineural hearing loss and ocular abnormalities. AS caused pathogenic variants in COL4A3 , COL4A4 or COL4A5 which encode the α3, α4 α5 chains of type IV collagen that forms a heterotrimer expressed glomerular basement membrane. Knowledge its genetic basis has informed development different models dogs, mice rat reflect autosomal X-linked inheritance patterns as well mutation types, including protein...
Podocytes are highly specialized, terminally differentiated cells in the glomerulus of kidney and these play a central role blood filtration. In this review, we comprehensively describe cell biology podocytes under healthy conditions glomerular disorders wherein podocyte injury is major pathological mechanism. First, molecular mechanisms that maintain actin cytoskeleton structure, permanent cycle exit, metabolism described. Secondly, injury, including genetic alterations external insults...
<h3>Importance</h3> International nephrology societies advise against nonsteroidal anti-inflammatory drug (NSAID) use in patients with hypertension, heart failure, or chronic kidney disease (CKD); however, recent studies have not investigated the frequency associations of these patients. <h3>Objectives</h3> To estimate and variation prescription NSAID among high-risk patients, to identify characteristics associated use, investigate whether is short-term, safety-related outcomes. <h3>Design,...
Glomerular hematuria has varied causes but can have a genetic basis, including Alport syndrome and IgA nephropathy.We used summary statistics to identify variants associated with in White British UK Biobank participants. Individuals glomerular were enriched by excluding participants genitourinary conditions. A strongly locus on chromosome 2 (COL4A4-COL4A3) was identified. The region reimputed using the Trans-Omics for Precision Medicine Program followed sequential rounds of regional...
PAX2 regulates kidney development, and its expression persists in parietal epithelial cells (PECs), potentially serving as a podocyte reserve. We hypothesized that mice with
Key Points Using transcriptome-wide association studies, we identified an between splicing out of exon 27 COL4A4 and hematuria. We confirmed the presence in independent cohort. Functional assays revealed that transcript with spliced affects collagen IV trimer assembly secretion. Background Hematuria is established sign glomerular disease can be associated kidney failure, but there has been limited scientific study this trait. Methods Here, combined genetic data from UK Biobank predicted gene...
Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of community, as well offer clarity for future clinical research sponsors, Syndrome Foundation hosted workshop to generate consensus recommendations prospective trials conventional drugs. Opinions key stakeholders were carefully considered, including those biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency and-most...