A5000593467- Neurofibromatosis and Schwannoma Cases
- Neuroblastoma Research and Treatments
- RNA Research and Splicing
- Craniofacial Disorders and Treatments
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Cleft Lip and Palate Research
- Testicular diseases and treatments
- Immune Cell Function and Interaction
- Glioma Diagnosis and Treatment
- Neurogenetic and Muscular Disorders Research
- Management of metastatic bone disease
- CAR-T cell therapy research
- Genomic variations and chromosomal abnormalities
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Spinal Hematomas and Complications
- Chromosomal and Genetic Variations
- dental development and anomalies
- Genetic Syndromes and Imprinting
- T-cell and B-cell Immunology
- Cancer-related gene regulation
- RNA regulation and disease
Centre Hospitalier Universitaire Sainte-Justine
2021-2022
McGill University
2019-2021
McGill University and Génome Québec Innovation Centre
2019
McGill Genome Centre
2019
Abstract Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with recurrent loss-of-function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying involved transcriptional silencing. To understand the role of PRC2 loss pathogenesis and identify therapeutic targets, we conducted parallel global epigenomic proteomic analysis archival formalin-fixed, paraffin-embedded (FFPE) human MPNST without (MPNSTLOSS vs. MPNSTRET). Loss resulted increased histone...
Abstract EFTUD2 is mutated in patients with mandibulofacial dysostosis microcephaly (MFDM). We generated a mutant mouse line conditional mutation Eftud2 and used Wnt1-Cre2 to delete it neural crest cells. Homozygous deletion of causes brain craniofacial malformations, affecting the same precursors as MFDM patients. RNAseq analysis embryonic heads revealed significant increase exon skipping increased levels an alternatively spliced Mdm2 transcript lacking 3. Exon was also O9-1 cells after...
Mutations in EFTUD2 are responsible for the autosomal dominant syndrome named MFDM (mandibulofacial dysostosis with microcephaly). However, it is not clear how reduced levels of cause abnormalities associated this syndrome. To determine if mouse can serve as a model uncovering etiology found patients, we used situ hybridization to characterize expression Eftud2 during development, and CRISPR/Cas9 generate mutant line deletion exon 2 gene. We that was expressed throughout embryonic though its...
Antigen-specific T cell expansion ex vivo followed by adoptive transfer enables targeting of a multitude microbial and cancer antigens. However, clinical-scale from rare precursors requires repeated stimulation, which may lead to dysfunction limited therapeutic potential. We used clinically compliant protocol expand Epstein-Barr virus (EBV) Wilms tumor 1 (WT1) antigen-specific CD8+ cells, leveraged exhaustion-associated inhibitory receptor blockade improve expansion. Several receptors were...
Summary EFTUD2, a GTPase and core component of the splicesome, is mutated in patients with mandibulofacial dysostosis microcephaly (MFDM). We generated mutant mouse line conditional mutation Eftud2 used Wnt1-Cre2 to delete it neural crest cells. Homozygous deletion leads cell death malformations brain craniofacial region embryos. RNAseq analysis embryonic heads revealed significant increase exon skipping, retained introns enriched levels Mdm2 transcripts lacking 3. Mutants also had increased...
<div>Abstract<p>Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with recurrent loss-of-function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying involved transcriptional silencing. To understand the role of PRC2 loss pathogenesis and identify therapeutic targets, we conducted parallel global epigenomic proteomic analysis archival formalin-fixed, paraffin-embedded (FFPE) human MPNST without (MPNST<sub>LOSS</sub> vs....
<p>Merged pdf file containing supplementary figures 1-4</p>
<p>Word file containing legends for supplemental figures S1-S4 and Supplemental tables 1-5</p>
<p>Word file containing legends for supplemental figures S1-S4 and Supplemental tables 1-5</p>
<p>Merged pdf file containing supplementary figures 1-4</p>
<div>Abstract<p>Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with recurrent loss-of-function alterations in polycomb-repressive complex 2 (PRC2), a histone-modifying involved transcriptional silencing. To understand the role of PRC2 loss pathogenesis and identify therapeutic targets, we conducted parallel global epigenomic proteomic analysis archival formalin-fixed, paraffin-embedded (FFPE) human MPNST without (MPNST<sub>LOSS</sub> vs....
Haploinsufficiency of EFTUD2 is associated with MFDM (mandibulofacial dysostosis microcephaly), but the etiology this syndrome remains unknown. Our goal to determine tissue and temporal specific expression requirement for Eftud2 during craniofacial development. We used RT‐PCR in situ hybridization examine embryogenesis. Using CRISPR/Cas9 we designed guide RNAs generate mice deletion ( del) conditional mutation exon 2 (Eftud2 flox) . At embryonic day (E) 7.5 8.5 mouse development, was highly...
Splicing, the removal of introns from pre‐messenger RNA is an essential step for expression most genes in multicellular organisms and expanding number proteins coded by genomes. Recently, exome sequencing revealed that mutations splicing factors small nuclear ribonucleoprotein particles (snRNPs) which form core components spliceosome, are responsible craniofacial malformations. Our group used situ hybridization to examine three spliceosome: Eftud2 – mutated patients with mandibulofacial...
Haploinsufficiency of EFTUD2 is associated with MFDM (mandibulofacial dysostosis microcephaly), but the etiology this syndrome remains unknown. Our goal to determine tissue and temporal requirement for Eftud2 during craniofacial development. We generated a mouse conditional mutation exon 2 ( flox ) using CRISPR/Cas9 editing system. used Wnt1‐Cre2 transgenic line delete specifically in neural crest cells. Embryos carrying one mutated allele were normal. However, when both alleles mutated, all...
Abstract Background The stimulation and expansion of antigen-specific T cells ex vivo enables the targeting a multitude cancer antigens. However, clinical scale T-cell from rare precursors requires repeated stimulations leading to terminal effector differentiation exhaustion that adversely impact therapeutic potential. We leveraged immune checkpoint blockade relevant CD8+ human improve function clinically Methods A clinically-compliant protocol relying on peptide-pulsed monocyte-derived...