Brian Krug
A5071409688- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Extracellular vesicles in disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Greenhouse Technology and Climate Control
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Diverse Educational Innovations Studies
- Chromosomal and Genetic Variations
- Immune Cell Function and Interaction
- Flowering Plant Growth and Cultivation
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Retinoids in leukemia and cellular processes
- Genomics and Phylogenetic Studies
- Cancer Research and Treatments
- Genetics and Neurodevelopmental Disorders
McGill University
2019-2024
Columbia University Irving Medical Center
2023
McGill University Health Centre
2018-2022
Centre For Human Genetics
2020
University of New Hampshire
2011
Abstract Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines isogenic CRISPR-edited controls to assess effects vitro vivo. We find that whereas H3K27me3 H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced H3.3K27M cells. unable spread from large unmethylated CpG islands, while can be outside these high-affinity sites but...
The discovery of H3K27M mutations in pediatric gliomas marked a new chapter cancer epigenomics. Numerous studies have investigated the effect this mutation on H3K27 trimethylation, but only recently we started to realize its additional effects epigenome. Here, use isogenic glioma H3K27M+/− cell lines investigate methylation and interaction with H3K36 H3K9 modifications. We describe "step down" distribution methylation: me3 is reduced me2, me2 me1, whereas H3K36me2/3 delineates boundaries for...
Abstract Background Point mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events pediatric gliomas. These point affect many chromatin modifications but exact oncogenic mechanisms currently unclear. Histone is known to localize nuclear compartments as promyelocytic leukemia (PML) bodies, which frequently mutated confirmed drivers acute leukemia. Results We find that glioma-associated disrupt formation of PML bodies this...
ADDITIONAL INDEX WORDS.greenhouse heating, nonchemical growth retardants, organic fertilizers C onsumer interest in environmentally friendly products has increased greenhouse growers' sustainable production techniques.It is estimated that consumers would spend up to 15% more for floricultural than conventionally produced products, and purchasers of herbaceous or plant tend be eco-friendly those who purchase woody materials (Behe et al., 2010;Hawkins 2011).In 2008, the Floriculture...
Polycomb Repressive Complex 2 (PRC2)-mediated histone H3K27 tri-methylation (H3K27me3) recruits canonical PRC1 (cPRC1) to maintain heterochromatin. In early development, polycomb-regulated genes are connected through long-range 3D interactions which resolve upon differentiation. Here, we report that polycomb looping is controlled by H3K27me3 spreading and regulates target gene silencing cell fate specification. Using glioma-derived H3 Lys-27-Met (H3K27M) mutations as tools restrict...
Abstract Diffuse Midline gliomas (DMGs) are grade IV tumors by the World Health Organization. They inoperable and resistant to chemo/radiotherapies resulting in a median survival of 8-11 months 5-year <2%. DMG is an epigenetic disease characterized mutations on histone H3.3 K27M global transcriptional reprogramming. This lacks appropriate models predict biology response treatment. Therefore, we developed novel syngeneic H3K27M mouse model using clinically relevant co-alterations...
Abstract Pediatric high-grade gliomas pHGG are lethal and frequently bear missense mutations in histone H3, which drive tumorigenesis by altering the epigenome cell fate/differentiation. While previous studies showed intrinsic contingencies associated with tumor development, limited information exists on microenvironment (TME) immune cells for these tumors. To define landscape of pediatric tumors at single-cell resolution, we profiled compared 69 samples using Chromium 10X technologies, H3.3...
Abstract Background: Glioblastoma is a grade IV malignant brain tumor with poor prognosis and rapid disease progression. Recurrent somatic mutations in histone H3 genes have been identified the majority of pediatric glioblastoma cases. The K27M mutation H3.1 H3.3 histones globally inhibits lysine methylation at K27 position, whereas G34R/V possibly affects K36 position. has shown to dramatically decrease total levels H3K27me3 H3K27me2 marks increase H3K27ac levels. However, effect on global...
Abstract Childhood tumors of the central nervous system are deadly diseases, and for many tumor types outcome has not improved over last three decades. Current evidence supports a model in which genetic alterations drive changes neurodevelopmental gene expression programs, leading to oncogenesis postnatally. We hypothesize that there specific cellular states during normal brain development vulnerable targets oncogenic mutations. However, comprehensive developmental data regions relevant...
The discovery of H3K27M mutations in pediatric gliomas marked a new chapter cancer epigenetics. Numerous studies have investigated the effect this mutation on H3K27 trimethylation, but only recently we started to realize its additional effects epigenome. Here, use isogenic glioma H3K27M(+/-) cell lines investigate methylation and interaction with H3K36 H3K9 modifications. We describe “Step Down” distribution methylation: me3 is reduced me2, me2 me1, while H3K36me2/3 delineate boundaries for...
Abstract BACKGROUND: Genomic and transcriptomic studies have elucidated new insights into the landscape of diffuse intrinsic pontine glioma (DIPG). However, role long non-coding RNAs (lncRNAs) has not been explored at depth in these tumors, there focused on how lncRNAs interact with K27M histone mutation. In a recent analysis nearly 200 DIPGs pediatric high-grade gliomas (pHGG), we previously detected novel, recurring structural variant lncRNA CCDC26. This rearrangement occurs 10% all DIPGs,...
Abstract Effective treatments are urgently needed for the incurable paediatric brainstem tumour Diffuse Midline Glioma (DMG). Most DMGs contain Histone H3 mutations (H3K27M), which produce extensive epigenetic dysregulation by inhibiting EZH2-mediated trimethylation of H3K27 (H3K27me3). Global depletion repressive H3K27me3 modification results in aberrantly open chromatin and is central to DMG tumorigenesis. Thus, targeting epigenome a promising avenue treatment DMG. We found that histone...
Abstract H3K27-mutant diffuse midline gliomas (DMGs) are defined as grade IV tumors by the World Health Organization. DMGs inoperable and resistant to chemo/radio therapies. Median survival ranges from 8-11 months, with 2% of patients surviving beyond 5 years. H3K27M mutations lead global epigenetic transcriptional reprogramming driven loss negative regulator H3K27 trimethylation (H3K27me3). Loss H3K27me3 is an initiating event in gliomagenesis. This disease lacks appropriate models predict...