A5034666118- Genetic and Kidney Cyst Diseases
- Renal and related cancers
- Renal Diseases and Glomerulopathies
- Biomedical Research and Pathophysiology
- Pediatric Hepatobiliary Diseases and Treatments
- T-cell and B-cell Immunology
- Genetic Syndromes and Imprinting
- Immune Cell Function and Interaction
- Intracranial Aneurysms: Treatment and Complications
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Moyamoya disease diagnosis and treatment
- Pediatric Urology and Nephrology Studies
- Genomics and Rare Diseases
- Liver physiology and pathology
- Cytokine Signaling Pathways and Interactions
- Pancreatic function and diabetes
- Genomic variations and chromosomal abnormalities
- Chronic Kidney Disease and Diabetes
- Renal cell carcinoma treatment
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Endoplasmic Reticulum Stress and Disease
- Urological Disorders and Treatments
Yale University
2016-2024
Whitney Museum of American Art
2023
Harvard University
2005-2008
Joslin Diabetes Center
2005-2008
Brigham and Women's Hospital
2005-2008
Jackson Laboratory
2005
Dominantly inherited isolated polycystic liver disease (PCLD) consists of cysts that are radiologically and pathologically identical to those seen in autosomal dominant kidney disease, but without clinically relevant cysts. The causative genes known for fewer than 40% PCLD index cases. Here, we have used whole exome sequencing a discovery cohort 102 unrelated patients who were excluded mutations the 2 most common genes, PRKCSH SEC63, identify heterozygous loss-of-function 3 additional ALG8,...
Evidence from animal models suggests that natural killer (NK) cells can be important players in the development of type 1 diabetes, although data humans are still sparse. We studied frequency and activation state blood NK at different stages human whether genetic or phenotypic cell peculiarities could associated with an early onset diabetes. The period is marked by a slight reduction cells, but these unusually activated some patients (γ-interferon expression). This status does not correlate,...
Significance Statement Dominantly inherited polycystic kidney and liver phenotypes occur when epithelial cells in these organs have reduction of polycystin-1 functional dosage. In a cohort genetically unresolved disease, the authors identified heterozygous loss function mutations ALG9 . encodes an endoplasmic reticulum enzyme that builds N -glycans, show Alg9 inactivation results impaired maturation. Using novel ‘genotype-first’ approach to ascertain individuals based strictly on their...
Thymic medullary epithelial cells (MECs) express a broad repertoire of peripheral-tissue antigens (PTAs), many which depend on the transcriptional regulatory factor Aire. Although Aire is known to be critically important for shaping self-tolerant T cell repertoire, its role in MEC maturation and function remains poorly understood. Using highly sensitive reproducible single-cell PCR assay, we demonstrate that individual Aire-expressing MECs transcribe subset PTA genes probabilistic fashion,...
Bilateral renal cystic disease presenting as chronic kidney (CKD) in adults is most commonly due to autosomal dominant polycystic (ADPKD). Genetic investigation of ADPKD cohorts identifies the underlying PKD1 (77%) or PKD2 mutation (15%) and up 8% cases remain "no PKD detected" (NMD).1Hwang Y.H. Conklin J. Chan W. et al.Refining genotype-phenotype correlation disease.J Am Soc Nephrol. 2016; 27: 1861-1868Crossref PubMed Scopus (89) Google Scholar Molecular characterization NMD-ADPKD by genome...
Identifying genes associated with rare diseases remains challenging due to the scarcity of patients and limited statistical power traditional association methods. Here, we introduce PERADIGM (Phenotype Embedding Similarity-based Rare Disease Gene Mapping), a novel framework that leverages natural language processing techniques integrate comprehensive phenotype information from electronic health records for disease gene discovery. employs an embedding model capture relationships between...
Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and pathophysiologic characteristics from other forms FSGS. This lesion occurs disproportionally patients carrying two APOL1 risk alleles, classic histologic resulting Human Immunodeficiency Virus (HIV) infection podocytes. Other viral infections, including parvovirus B19, drugs such interferon that perturb immune system, have been...
Genetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for disorder as potentially pathogenic variants can reside genes that are yet known to be involved disease. We have developed KidneyNetwork, utilizes tissue-specific expression inform candidate gene prioritization specifically diseases. KidneyNetwork is a novel method constructed by integrating RNA-sequencing co-expression network of 878 samples multi-tissue 31,499 samples. It uses patterns...
The three members of the costimulatory receptor family, CD28, CTLA-4, and ICOS, have complementary effects on T cell activation, their balance controls overall outcome immune autoimmune responses. They are encoded in a short genomic interval, activity may result from interplay between allelic variants at each locus. With multiethnic DNA panels that represent wide spectrum human populations, we demonstrate long-range linkage disequilibrium among genes. A large fraction variation found locus...
Expanded mutation detection and novel gene discovery for isolated polycystic liver disease (PCLD) are necessary as 50% of cases do not have identified mutations in the seven published genes. We investigated a family with five affected siblings which no loss-of-function variants were by whole exome sequencing analysis. SNP genotyping linkage analysis narrowed candidate regions to ∼8% genome, included two PCLD genes close proximity each other, GANAB LRP5. Based on these findings, we...
Significance Statement Heterozygous DNAJB11 mutation carriers manifest with small cystic kidneys and renal failure in adulthood. Recessive cases prenatal kidney dysplasia were recently described. Our vitro mouse model studies investigate the proposed disease mechanism as an overlap of autosomal-dominant polycystic tubulointerstitial pathogenesis. We find that loss impairs cleavage maturation protein polycystin-1 (PC1) results dosage-dependent cyst formation mice. Dnajb11 does not activate...
In humans and in animal models, susceptibility to arthritis is under complex genetic control, reflecting influences on the immunological processes that initiate autoimmunity subsequent inflammatory mechanisms joints. The effector phases are conveniently modeled by K/BxN serum transfer system, a robust model well suited for analysis where initiated pathogenic Ig. Here, we mapped loci distinguishing high-responder BALB/c vs. low-responder SJL strains. After computational modeling of potential...
Patient variants in Tubby Like Protein-3 (TULP3) have recently been associated with progressive fibrocystic disease tissues and organs. TULP3 is a ciliary trafficking protein that links membrane-associated proteins to the intraflagellar transport complex A. In mice, mutations Tulp3 drive phenotypes consistent dysfunction which include renal cystic disease, as part of ciliopathic spectrum. Here we report two sisters from consanguineous parents hepatic harboring homozygous missense mutation...
Autosomal dominant polycystic liver disease is a rare condition with female preponderance, based mainly on pathogenic variants in 2 genes, PRKCSH and SEC63. Clinically, autosomal characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little known about the prediction of progression at early stages, hindering clinical management, genetic counseling, design randomized controlled trials. improve prognostication, we built consortium European...
See Commentary on Page 575 Autosomal dominant polycystic kidney disease (ADPKD) is caused by loss-of-function or deleterious mutations in the PKD1 PKD2 genes and seen with a prevalence of 1:400 to 1:1000.1Torres V.E. Harris P.C. Pirson Y. disease.Lancet. 2007; 369: 1287-1301Abstract Full Text PDF PubMed Scopus (909) Google Scholar Patients develop liver cysts that accumulate expand crowd out normal organ parenchyma lead failure half patients age 60 years.2Harris Torres Polycystic...
Background A major difference between autosomal recessive polycystic kidney disease (ARPKD) and dominant (ADPKD) lies in the pattern of inheritance, resultant timing focality cyst formation. In both diseases, cysts form liver as a consequence cellular genotype respective gene, but this occurs by germline inheritance ARPKD somatic second hit mutations to one normal allele ADPKD. The fibrocystic phenotype is attributed abnormal ductal plate formation because absence PKHD1 expression during...