Shareef Nahas
A5066292574- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Prenatal Screening and Diagnostics
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Acute Myeloid Leukemia Research
- Congenital Heart Disease Studies
- Acute Lymphoblastic Leukemia research
- Immunodeficiency and Autoimmune Disorders
- Effects of Radiation Exposure
- SARS-CoV-2 detection and testing
- Genomic variations and chromosomal abnormalities
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Polyomavirus and related diseases
- Hedgehog Signaling Pathway Studies
- Cell Image Analysis Techniques
- Chromosomal and Genetic Variations
Children’s Institute
2017-2025
Infinity (United States)
2022-2024
Rady Children's Hospital-San Diego
2017-2023
University of Washington
2019
Sequenom (United States)
2019
LabCorp (United States)
2019
University of California, San Diego
2018
University of California, Los Angeles
2003-2017
Novartis (United States)
2014-2015
California NanoSystems Institute
2009
Abstract Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic time to change acute medical or surgical management (clinical utility) improve outcomes acutely ill We report retrospective cohort study inpatient infants regional children’s hospital from July 2016–March 2017. Forty-two families received rWGS for etiologic diagnosis disorders. Probands also standard testing as clinically indicated. Primary...
Automated phenotyping and interpretation of rapid whole-genome sequencing improve time to diagnosis genetic diseases in hospitalized children.
Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU United States. Although individually rare, there over 6,200 single-gene diseases, which may preclude genetic diagnosis prior admission. Rapid whole genome sequencing is an emerging method of diagnosing conditions time affect management neonates; however, its clinical utility has yet be adequately demonstrated critically ill children. This study evaluates next-generation pediatric critical care.Retrospective...
While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians lack familiarity with these diseases, timely molecular diagnosis may improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for disease and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, superior analytic...
Approximately 14% of genetic mutations in patients with ataxia-telangiectsia (A-T) are single-nucleotide changes that result primary premature termination codons (PTCs), either UAA, UAG, or UGA. The purpose this study was to explore a potential therapeutic approach for subset by using aminoglycosides induce PTC read-through, thereby restoring levels full-length ATM (A-T mutated) protein. In experiments modified vitro cDNA coupled transcription/translation protein truncation test, 13 A-T cell...
Ataxia-telangiectasia (A-T) is an autosomal recessive neurological disorder caused by mutations in the ATM gene. Classical splicing (type I) delete entire exons during pre-mRNA splicing. In this report, we describe nine examples of nonclassical 12 A-T patients and compare cDNA changes to estimates splice junction strengths based on maximum entropy modeling. These fall into three categories: pseudoexon insertions II), single nucleotide within exon III), intronic that disrupt conserved 3'...
Large numbers of genetic disorders are caused by nonsense mutations for which compound-induced readthrough premature termination codons (PTCs) might be exploited as a potential treatment strategy. We have successfully developed sensitive and quantitative high-throughput screening (HTS) assay, protein transcription/translation (PTT)–enzyme-linked immunosorbent assay (ELISA), identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T) disease model. This HTS PTT-ELISA is...
The Centers for Disease Control and Prevention contracted with laboratories to sequence the SARS-CoV-2 genome from positive samples across United States enable public health officials investigate impact of variants on disease severity as well effectiveness vaccines treatment. Herein we present initial results correlating RT-PCR quality control metrics sample collection sequencing methods full viral genomic 24,441 patient between April June 2021.RT-PCR confirmed (N Gene Ct value < 30)...
Universal newborn screening (NBS) is a highly successful public health intervention. Archived dried bloodspots (DBS) collected for NBS represent rich resource population genomic studies. To fully harness this in such studies, DBS must yield high-quality DNA (gDNA) whole genome sequencing (WGS). In pilot study, we hypothesized that gDNA of sufficient quality and quantity WGS could be extracted from archived up to 20 years old without PCR (Polymerase Chain Reaction) amplification. We describe...
The functional consequences of missense variants are often difficult to predict. This becomes especially relevant when DNA sequence changes used determine a diagnosis or prognosis. To analyze the 12 in patients with mild forms ataxia-telangiectasia (A-T), we employed site-directed mutagenesis mutated (ATM) cDNA followed by stable transfections into single A-T cell line isolate effects each allele on cellular phenotype. After induction transfected cells CdCl2, monitored for successful ATM...
Chemical-induced read through of premature stop codons might be exploited as a potential treatment strategy for genetic disorders caused by nonsense mutations. Despite the promise this approach, only few read-through compounds (RTCs) have been discovered to date. These include aminoglycosides (e.g., gentamicin and G418) nonaminoglycosides PTC124 RTC13). The therapeutic benefits these RTCs remain determined. In an effort find new RTCs, we screened additional ~36,000 small molecular weight...
Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of disease that differ terms molecular characteristics and patient outcomes. Despite this heterogeneity, patients with medulloblastoma receive similar therapies, including surgery, radiation, intensive chemotherapy. Although these treatments prolong survival, many still die from survivors suffer severe long-term side effects therapy. We hypothesize each...
ATM plays a critical role in cellular responses to DNA double-strand breaks (DSBs). We describe new ATM–mediated DSB–induced damage response pathway involving microRNA (miRNA): irradiation (IR)-induced DSBs activate ATM, which leads the downregulation of miR-335, miRNA that targets CtIP, is an important trigger end resection homologous recombination repair (HRR). demonstrate CREB responsible for large portion miR-335 expression by binding promoter region miR-335. greatly reduced after IR,...
Abstract Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes known cause recessive, early-onset severe multi-organ diseases. VARS encodes the only valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with different missense variants . Subjects present a range of global developmental delay, epileptic...
Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups ependymoma are supratentorial ZFTA-fusion associated posterior fossa group A. In both groups, tumors occur mainly in young children frequently recur after treatment. Although mechanisms underlying these diseases have recently been uncovered, they remain difficult to target innovative therapeutic approaches urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C),...