A5038287284- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Biomedical Research and Pathophysiology
- Genetic Syndromes and Imprinting
- Hedgehog Signaling Pathway Studies
- Microtubule and mitosis dynamics
- Protist diversity and phylogeny
- Renal Diseases and Glomerulopathies
- Fetal and Pediatric Neurological Disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Cerebrospinal fluid and hydrocephalus
- Renal cell carcinoma treatment
- Pediatric Urology and Nephrology Studies
- Cystic Fibrosis Research Advances
- Healthcare cost, quality, practices
- Dialysis and Renal Disease Management
- Organ Donation and Transplantation
- Amino Acid Enzymes and Metabolism
- Genetics and Neurodevelopmental Disorders
- Health and Medical Research Impacts
- Urological Disorders and Treatments
- Cellular transport and secretion
Yale University
2015-2024
The University of Texas Southwestern Medical Center
2002-2015
Advanced Center for Chronic Diseases
2015
University of Kansas Medical Center
2015
Advanced Imaging Research (United States)
2011
National Institutes of Health
2010
Charité - Universitätsmedizin Berlin
2009
Pediatrics and Genetics
2007
University of Nebraska Medical Center
2005
University of New Haven
2000-2005
A second gene for autosomal dominant polycystic kidney disease was identified by positional cloning. Nonsense mutations in this ( PKD2 ) segregated with the three families. The predicted 968-amino acid sequence of product has six transmembrane spans intracellular amino- and carboxyl-termini. protein amino similarity PKD1, Caenorhabditis elegans homolog family voltage-activated calcium (and sodium) channels, it contains a potential calcium-binding domain.
Polycystic kidney disease (PKD) is the most common genetic cause of renal failure in humans. Several proteins that are encoded by genes associated with PKD have recently been identified primary cilia tubular epithelia. These findings suggested abnormalities formation and function may play a role pathogenesis PKD. To directly determine whether essential to maintain integrity, we conditionally inactivated KIF3A, subunit kinesin-II for formation, Constitutive inactivation KIF3A produces...
Germline mutations in PKD2 cause autosomal dominant polycystic kidney disease. We have introduced a mutant exon 1 tandem with the wild-type at mouse Pkd2 locus. This is an unstable allele that undergoes somatic inactivation by intragenic homologous recombination to produce true null allele. Mice heterozygous and homozygous for this mutation, as well Pkd+/- mice, develop liver lesions are indistinguishable from human phenotype. In all cases, renal cysts arise tubular cells lose capacity...
DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we large polymorphic deletion that encodes tandem repeats putative brain-related transcription factor binding sites in intron 2 DCDC2 . Alleles this compound repeat are significant disequilibrium multiple traits. RT-PCR data show localizes to regions brain where fluent occurs, and RNA interference studies down-regulation...
Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on short arm of chromosome 16, but in about 4 percent families with disorder it unknown mutations elsewhere genome. The natural course both genetic forms not well characterized.We studied 17 autosomal to compare presymptomatic diagnosis ultrasonography genetic-linkage studies and relate clinical variation whether mutation was implicated.In 10 found cosegregate polymorphic DNA markers flanking...
Polycystic kidney disease (PKD) is an inherited disorder that characterized by the accumulation of cysts in renal parenchyma and progressive decline function. Recent studies suggest PKD arises from abnormalities primary cilium. We have previously shown kidney-specific inactivation ciliogenic gene Kif3a during embryonic development produces failure. Here, we used tamoxifen-inducible, targeting to inactivate postnatal mouse kidney. Kidney-specific newborn mice resulted loss cilia produced...
Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion abnormal proliferation of cyst-lining epithelial cells. The chloride channel the cystic fibrosis transmembrane conductance regulator (CFTR) participates fluid, mammalian target rapamycin (mTOR) pathway may drive CFTR mTOR are negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug wide clinical use, is pharmacological activator AMPK. We find that...
Numerous genes for monogenic kidney diseases with classical patterns of inheritance, as well complex that manifest in combination environmental factors, have been discovered. Genetic findings are increasingly used to inform clinical management nephropathies, and led improved diagnostics, disease surveillance, choice therapy, family counseling. All these steps rely on accurate interpretation genetic data, which can be outpaced by current rates data collection. In March 2021, Kidney Diseases:...
<i>PKD2</i>, the second gene for autosomal dominant polycystic kidney disease (ADPKD), encodes a protein, polycystin-2, with predicted structural similarity to cation channel subunits. However, function of polycystin-2 remains unknown. We used polyclonal antisera specific intracellular NH<sub>2</sub> and COOH termini identify as an ∼110-kDa integral membrane glycoprotein. Polycystin-2 from both native tissues cells in culture is sensitive Endo H suggesting continued presence high-mannose...
Ksp-cadherin is a unique, tissue-specific member of the cadherin family cell adhesion molecules that expressed in tubular epithelial cells kidney and developing genitourinary (GU) tract. It has recently been shown 1341-bp fragment 5' flanking region containing gene promoter can recapitulate complete expression pattern GU Similar to endogenous gene, transgenes 1341 bp are nephrons, ureteric bud, mesonephric tubules, Wolffian duct, Müllerian duct. In adult mice, restricted renal tubules....
Mutations in PRKCSH, encoding the β-subunit of glucosidase II, an N-linked glycan-processing enzyme endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations SEC63, a component protein translocation machinery ER, also this These findings are suggestive role for cotranslational protein-processing pathways maintaining epithelial luminal structure and implicate noncilial ER proteins human
Polycystin-1, which is encoded by a gene that mutated in autosomal dominant polycystic kidney disease (ADPKD), involved cell-matrix interactions as well ciliary signaling. The precise mechanisms it functions, however, remain unclear. Here we find polycystin-1 undergoes proteolytic cleavage releases its C-terminal tail (CTT), enters the nucleus and initiates signaling processes. occurs vivo association with alterations mechanical stimuli. Polycystin-2, product of second ADPKD, modulates...