A5100335605- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Renal Diseases and Glomerulopathies
- Renal cell carcinoma treatment
- Urological Disorders and Treatments
- Pediatric Urology and Nephrology Studies
- Congenital heart defects research
- Liver Disease and Transplantation
- Traditional Chinese Medicine Studies
- Lymphatic System and Diseases
- Cancer-related molecular mechanisms research
- Liver Disease Diagnosis and Treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Hedgehog Signaling Pathway Studies
- Wnt/β-catenin signaling in development and cancer
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Medical Imaging and Pathology Studies
- Connexins and lens biology
- Peroxisome Proliferator-Activated Receptors
- Genetic Syndromes and Imprinting
- Intraocular Surgery and Lenses
- Immune Response and Inflammation
- Pediatric Hepatobiliary Diseases and Treatments
- Cancer Mechanisms and Therapy
Boston Medical Center
2015-2025
Boston University
2016-2025
Harvard University
1997-2022
Boston Children's Hospital
2022
Gaozhou People's Hospital
2022
University Medical Center
2007-2020
Huazhong University of Science and Technology
2016-2019
Jiangsu Provincial Center for Disease Control and Prevention
2019
Shanghai Sixth People's Hospital
1997-2017
Shanghai Jiao Tong University
2017
Background Congenital anomalies of the kidney and urinary tract (CAKUT) are most prevalent cause disease in first three decades life. Previous gene panel studies showed monogenic causation up to 12% patients with CAKUT. Methods We applied whole-exome sequencing analyze genotypes individuals from 232 families CAKUT, evaluating for mutations single genes known human CAKUT mice. In consanguineous or multiplex families, we additionally performed a search novel causes Results 29 (13%), detected...
The murine autosomal recessive juvenile cystic kidney (jck) mutation results in polycystic disease. We have identified jck mice a Nek8, novel and highly conserved member of the Nek kinase family. In vitro expression mutated Nek8 enlarged, multinucleated cells with an abnormal actin cytoskeleton. To confirm that defect gene can cause disease, we performed cross-species analysis: injection zebrafish embryos morpholino anti-sense oligonucleotide corresponding to ortholog resulted formation...
Cardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe 46,XY,t(1;5)(p36.11;q31.2)dn translocation carrier with pervasive developmental delay who also exhibited LVOT defects, including bicuspid aortic valve (BAV), coarctation the aorta (CoA) and patent ductus arteriosus (PDA). The 1p breakpoint disrupts 5′ UTR AHDC1, encodes AT-hook DNA-binding motif...
Transmission electron microscopy (TEM) images can visualize kidney glomerular filtration barrier ultrastructure, including the basement membrane (GBM) and podocyte foot processes (PFP). Podocytopathy is associated with morphological changes observed experimentally clinically by measuring GBM or PFP width. However, these measurements are currently performed manually. This limits research on podocytopathy disease mechanisms therapeutics due to labor intensiveness inter-operator variability. We...
A high level of polycystin-1 expression is detected in kidneys all patients with autosomal dominant polycystic kidney disease (ADPKD). Mice that overexpress also develop renal cysts. Whether overexpression necessary for cyst formation still unclear. Here, we report the generation a targeted mouse mutant null mutation Pkd1 and its phenotypic characterization comparison del34 mutants carry 'truncation mutation' Pkd1. We show homozygotes same, but more aggressive, pancreatic cystic as...
Three founder transgenic mice were generated with a 108 kb human genomic fragment containing the entire autosomal dominant polycystic kidney disease (ADPKD) gene, PKD1, plus tuberous sclerosis TSC2. Two lines established (TPK1 and TPK3) each approximately 30 copies of transgene. Both produced full-length PKD1 mRNA polycystin-1 protein that was developmentally regulated, similar to endogenous pattern, expression during renal embryogenesis neonatal life, markedly reduced at conclusion...
Complex central nervous system (CNS) malformations frequently coexist with other developmental abnormalities, but whether the associated defects share a common genetic basis is often unclear. We describe five individuals who phenotypically related CNS and in some cases urinary tract defects, also haploinsufficiency for NFIA transcription factor gene due to chromosomal translocation or deletion. Two have balanced translocations that disrupt NFIA. A third individual two half-siblings an...
PKD1, the gene that is mutated in approximately 85% of autosomal dominant polycystic kidney disease (ADPKD) cases humans, has recently been identified (Eur. PKD Consortium. Cell 77: 881-894, 1994; also, erratum 78: 1994). The longest open-reading frame PKD1 encodes polycystin, a novel 460-kDa protein contains series NH2-terminal adhesive domains (J. Hughes, C. J. Ward, B. Peral, R. Aspinwall, K. Clark, San Millan, V. Gamble, and P. Harris. Nat. Genet. 10: 151-160, 1995; Int. 81: 289–298,...
Robo2 is the cell surface receptor for repulsive guidance cue Slit and involved in axon neuronal migration. Nephrin a podocyte slit-diaphragm protein that functions kidney glomerular filtration barrier. Here, we report expressed at basal of mouse podocytes colocalizes with nephrin. Biochemical studies indicate forms complex nephrin through adaptor Nck. In contrast to role promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced polymerization. addition, amount F-actin...
Congenital anomalies of the kidney and urinary tract (CAKUT) are most common cause CKD in first three decades life. However, for patients with CAKUT, causative mutation remains unknown. We identified a kindred an autosomal dominant form CAKUT. By whole-exome sequencing, we heterozygous truncating (c.279delG, p.Trp93fs*) nuclear receptor interacting protein 1 gene ( NRIP1 ) all seven affected members. encodes transcriptional cofactor that directly interacts retinoic acid receptors (RARs) to...
The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney development podocyte foot process structure, but the SLIT2/ROBO2 signaling mechanism regulating function is not known. Here we report that a potentially novel pathway consisting of SLIT/ROBO Rho GTPase activating protein 1 (SRGAP1) nonmuscle myosin IIA (NMIIA) regulates adhesion downstream ROBO2. We found II regulatory light chain (MRLC), subunit NMIIA, interacts directly with SRGAP1 forms complex...