A5102984331- Retinal Development and Disorders
- RNA regulation and disease
- Clostridium difficile and Clostridium perfringens research
- interferon and immune responses
- Gut microbiota and health
- Retinal Diseases and Treatments
- Genomics and Rare Diseases
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Photoreceptor and optogenetics research
- Lysosomal Storage Disorders Research
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Extracellular vesicles in disease
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- Genetic and Kidney Cyst Diseases
- Nosocomial Infections in ICU
- Chronic Lymphocytic Leukemia Research
- Advanced Proteomics Techniques and Applications
- Mast cells and histamine
- Helicobacter pylori-related gastroenterology studies
- Identification and Quantification in Food
- S100 Proteins and Annexins
- Microscopic Colitis
Harvard University
2017-2025
Massachusetts Eye and Ear Infirmary
2017-2025
New York Genome Center
2016
McGill University and Génome Québec Innovation Centre
2015
McGill University
2015
Abstract Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations ubiquitously expressed genes non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 ( PRPF31 -mutated) patient-derived organoids and pigment epithelium (RPE), as well Prpf31 +/− mouse tissues, which revealed that disrupted alternative splicing occurred for specific programmes. Mis-splicing of encoding proteins was limited to...
Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk developing CDI because they exposed to C. spores through contact with hospital environment and often receive antibiotics other medications that can disrupt integrity indigenous intestinal microbiota impair colonization resistance. Using whole metagenome shotgun sequencing, we examined diversity composition fecal in a prospective cohort study 98...
Clostridium difficile infection (CDI) is intricately linked to the health of gastrointestinal tract and its indigenous microbiota. In this study, we assessed whether fecal excretion host DNA associated with CDI development. Assuming that shedding epithelial cell increases in inflamed intestine, used human as a marker intestinal insult. Whole-genome shotgun sequencing was employed quantify evaluate bacterial content samples collected from patients incipient CDI, hospitalized controls, healthy...
Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream start codon ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in South Asian and African ancestry, respectively. Genotypes included 71 homozygotes 3 mixed heterozygotes trans with a predicted loss-of-function allele. Haplotype showed single-nucleotide variants (SNVs)...
Inherited retinal degenerations (IRDs) are at the focus of current genetic therapeutic advancements. For a treatment such as gene therapy to be successful, an accurate diagnostic is required. Genetic diagnostics relies on assessment probability that given DNA variant pathogenic. Non-coding variants present unique challenge for assessments compared coding variants. one, non-coding much higher number in genome than In addition, our understanding rules govern regions less complete regions....
Mutations in NMNAT1, a key enzyme involved the synthesis of NAD+ nucleus, lead to an early onset severe inherited retinal degeneration (IRD). We aimed understand role nuclear retina and identify molecular mechanisms underlying NMNAT1-associated disease, using mouse model that harbors p.V9M mutation Nmnat1 (Nmnat1V9M/V9M). identified temporal transcriptional reprogramming retinas Nmnat1V9M/V9M mice prior degeneration, which begins at 4 weeks age, with no significant alterations gene...
Summary Mutations in pre-mRNA processing factors (PRPFs) cause 40% of autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations ubiquitously expressed PRPFs retinal disease. To understand the molecular basis this phenotype, we have generated RP type 11 (PRPF31- mutated) patient-specific organoids and pigment epithelium (RPE) from induced pluripotent stem cells (iPSC). Impaired alternative splicing genes encoding proteins occurred Prpf31 +/− mouse retinae, not fibroblasts...
Abstract Purpose Inconclusive interpretation of pathogenicity variants is a common problem in Mendelian disease diagnostics. We hypothesized that some unknown significance (VUS) may lead to aberrant pre-mRNA splicing. To address this we have developed high throughput splicing assay (HTSA) than can be utilized test the effects 1000s on exon recognition. Methods 2296 reference, control and variant sequences from 380 exons 89 genes associated with inherited retinal degenerations (IRDs) were...
Abstract High-throughput transcriptome sequencing has become a powerful tool in the study of human diseases. Identification causal mechanisms may entail analysis differential gene expression (DGE), transcript/isoform (DTE) and identification, classification quantification alternative splicing (AS) and/or detection novel AS events. For such global profiling execution multi-level data methodologies is required. Each level presents its own unique challenges questions about their performance...
Abstract Purpose With the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision-making. Yet cause disease cannot be identified using exon-based sequencing a significant portion patients. We hypothesized that non-coding mutations contribute significantly to causality IRDs and evaluated patients with single coding RPGRIP1 test this hypothesis. Methods IRD families underwent targeted panel sequencing. Unsolved...
Abstract Inherited retinal degenerations (IRDs) are at the focus of current genetic therapeutic advancements. For a treatment such as gene therapy to be successful an accurate diagnostic is required. Genetic diagnostics relies on assessment probability that given DNA variant pathogenic. Non-coding variants present unique challenge for assessments compared coding variants. one, non-coding much higher number in genome than In addition, our understanding rules govern regions less complete...
Abstract Retinitis pigmentosa (RP), is the most common inherited retinal degeneration (IRD), leading to vision loss via dysfunction and death of photoreceptor cells pigment epithelium (RPE). Mutations in pre-mRNA processing factor 31 ( PRPF31 ) gene are associated with autosomal dominant RP, impairing RPE function. While adeno-associated virus (AAV)-mediated therapy shows promise for treating IRDs, slow progression these diseases often makes timely measurement clinical efficacy challenging....
ABSTRACT Rod cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1/3500 people. Over 270 genes are be implicated in the retinal degenerations (IRDs), yet genetic diagnosis for ∼30% IRD of patients remains elusive despite advances sequencing technologies. The goal this study was determine causality a family with Rod-cone (RCD). Family members were given full ophthalmic exam at Retinal Service MEE and consented testing. Whole...
Rod cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1/3500 people. Over 270 genes are be implicated in the retinal degenerations (IRDs), yet genetic diagnosis for ~30% IRD of patients remains elusive despite advances sequencing technologies. The goal this study was determine causality a family with Rod-cone (RCD). Family members were given full ophthalmic exam at Retinal Service MEE and consented testing. Whole exome (WES)...