A5007884388- Connective tissue disorders research
- Bone and Dental Protein Studies
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Bone fractures and treatments
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Biochemical and Molecular Research
- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- Bone health and osteoporosis research
- Hip disorders and treatments
- Diet and metabolism studies
- RNA modifications and cancer
- Vitamin K Research Studies
- Nitric Oxide and Endothelin Effects
- Neurogenetic and Muscular Disorders Research
- Neonatal Respiratory Health Research
- RNA regulation and disease
- ATP Synthase and ATPases Research
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Cardiovascular and Diving-Related Complications
- Genetics and Neurodevelopmental Disorders
Baylor College of Medicine
2015-2024
Texas Children's Hospital
2015-2024
Social Service Sericulture Project Trust
2023
Montreal Children's Hospital
2018
McGill University
2018
Baylor Genetics
2017
Weizmann Institute of Science
2016
Christian Medical College & Hospital
1992
Christian Medical College
1992
Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies not been tested in clinical trials for OI treatment.
Abstract Coffin–Siris and Nicolaides–Baraitser syndromes (CSS NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures individuals with various subtypes CSS ( ARID1B , SMARCB1 SMARCA4 ) NCBRS SMARCA2 ). demonstrate that degree similarity some can be greater than within CSS, indicating a link functional basis two syndromes. show chromosome 6q25 microdeletion syndrome, harboring...
Alu repetitive elements are known to be major contributors genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported CNVs simple deletions and duplications, mechanism underlying Alu–Alu-mediated rearrangement has been attributed non-allelic homologous recombination (NAHR). Chromosome 17 at p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for elements, with a fraction 30% total sequence annotated in human...
BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling a pathogenic mechanism in OI. Here, we evaluated children with OI and conducted phase I clinical trial of inhibition adults OI.METHODSHistology RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set analysis (GSEA), Ingenuity Pathway Analysis (IPA) used to identify dysregulated pathways....
Osteogenesis imperfecta ( OI ) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding genetic basis , there have been no large‐scale natural history studies. To better understand improve care patients, a network Linked Clinical Research Centers LCRC was established. Subjects with were enrolled longitudinal study, this report, we present cross‐sectional data on largest cohort subjects n = 544). type...
In a large cohort of osteogenesis imperfecta type V (OI V) patients (17 individuals from 12 families), we identified the same mutation in 5' untranslated region (5'UTR) interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) provide detailed description their phenotype. This leads to creation novel start codon adding five residues IFITM5 was recently reported several other OI families. The variability phenotype quite even within...
The structural maintenance of chromosomes (SMC) family proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome are linked rare breakage disorders. Here, we have identified a syndrome associated with severe lung disease early childhood. Four children from two unrelated kindreds died pulmonary during infancy following viral pneumonia evidence combined T B cell immunodeficiency. Whole exome sequencing revealed biallelic missense...
Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO disease pathogenesis remain unclear, preventing implementation NO-related therapy. Argininosuccinate lyase (ASL) is only enzyme able to produce arginine, substrate for generation by nitric synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice combination with genetic chemical colitis models. We demonstrate that derived...
Previous studies have shown that nitric oxide (NO) supplements may prevent bone loss and fractures in preclinical models of estrogen deficiency. However, the mechanisms by which NO modulates anabolism remain largely unclear. Argininosuccinate lyase (ASL) is only mammalian enzyme capable synthesizing arginine, sole precursor for synthase-dependent (NOS-dependent) synthesis. Moreover, ASL also required channeling extracellular arginine to NOS production. deficiency (ASLD) thus a model study...
Exon-targeted microarrays can detect small (<1000 bp) intragenic copy number variants (CNVs), including those that affect only a single exon. This genome-wide high-sensitivity approach increases the molecular diagnosis for conditions with known disease-associated genes, enables better genotype–phenotype correlations, and facilitates variant allele detection allowing novel disease gene discovery. We retrospectively analyzed data from 63,127 patients referred clinical chromosomal microarray...
Downregulation of the urea cycle enzyme argininosuccinate synthase (ASS1) by either promoter methylation or HIF1α is associated with increased metastasis and poor prognosis in multiple cancers. We have previously shown that normoxic conditions, ASS1 downregulation facilitates cancer cell proliferation increasing aspartate availability for pyrimidine synthesis complex CAD. Here we report hypoxia, expression cancerous cells downregulated further HIF1α-mediated induction miR-224-5p, making more...
Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that systematically evaluated pulmonary function individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) expiratory volume the first second (FEV1 ), large cohort of OI (n = 217) enrolled multicenter, observational study. show more severe form disease, type III, significantly reduced FVC FEV1 which do...