A5069773213- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Cancer, Lipids, and Metabolism
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- Hemoglobinopathies and Related Disorders
- Histone Deacetylase Inhibitors Research
- Chromosomal and Genetic Variations
- Prenatal Screening and Diagnostics
- Cancer-related gene regulation
- Genomics and Phylogenetic Studies
- Chronic Myeloid Leukemia Treatments
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Plant Molecular Biology Research
- Folate and B Vitamins Research
- Machine Learning in Bioinformatics
- Angiogenesis and VEGF in Cancer
- Gene expression and cancer classification
University of Southern California
2022-2024
Van Andel Institute
2019-2023
McGill University
2010-2020
Dalian University of Technology
2016
Institute for Research in Immunology and Cancer
2012
Université de Montréal
2012
Tumor suppressor SMARCA4 (BRG1), a key SWI/SNF chromatin remodeling gene, is frequently inactivated in cancers and not directly druggable. We recently uncovered that loss an ovarian cancer subtype causes cyclin D1 deficiency leading to susceptibility CDK4/6 inhibition. Here, we show this vulnerability conserved non-small cell lung (NSCLC), where also results reduced expression selective sensitivity inhibitors. In addition, SMARCA2, another subunit lost subset of NSCLCs, regulates drug...
Spatial chromatin organization is emerging as an important mechanism to regulate the expression of genes. However, very little known about genome architecture at high-resolution in vivo . Here, we mapped three-dimensional human Hox clusters with chromosome conformation capture (3C) technology. We show that computational modeling 3C data sets can identify candidate regulatory proteins and gene expression. genes encode evolutionarily conserved master regulators development which strict control...
Abstract Inactivating mutations in SMARCA4 ( BRG1 ), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to inhibition cyclin-dependent kinase 4/6 (CDK4/6). loss causes profound downregulation cyclin D1, which limits CDK4/6 activity leads vitro vivo susceptibility inhibitors. patient...
Thousands of long non-coding RNAs (lncRNAs) have been identified in mammals, many which represent important regulators gene expression. However, the mechanisms used by lncRNAs to control transcription remain largely uncharacterized. Here, we report on HOTAIRM1, a promising lncRNA biomarker leukemia and solid tumors. We find that HOTAIRM1 contributes three-dimensional chromatin organization changes required for temporal collinear activation HOXA genes. show distinct variants preferentially...
Several types of collagen contain cryptic antiangiogenic noncollagenous domains that are released upon proteolysis extracellular matrix (ECM). Among those is Arresten, a collagen-derived factor (CDAF) processed from α1 IV. However, the conditions under which Arresten IV in vivo or whether protein functions tumor suppressor pathways remain unknown. Here, we show p53 induces expression and release Arresten-containing fragments ECM. Comparison transcriptional activation COL4A1 with other...
Although DNA N 6 -adenine methylation (6mA) is best known in prokaryotes, its presence eukaryotes has recently generated great interest. Biochemical and genetic evidence supports that AMT1, an MT-A70 family methyltransferase (MTase), crucial for 6mA deposition unicellular eukaryotes. Nonetheless, the transmission mechanism remains to be elucidated. Taking advantage of single-molecule real-time circular consensus sequencing (SMRT CCS), here we provide definitive semiconservative Tetrahymena...
Abstract The resolution of chromatin conformation capture technologies keeps increasing, and the recent nucleosome contact maps allow us to explore how fine-scale 3D organization is related epigenomic states in human cells. Using publicly available Micro-C datasets, we develop a deep learning model, CAESAR, learn mapping function from features organization. model accurately predicts structures, such as short-range loops stripes, that Hi-C fails detect. With existing datasets ENCODE Roadmap...
The human genome must be tightly packaged in order to fit inside the nucleus of a cell. Genome organization is functional rather than random, which allows for proper execution gene expression programs and other biological processes. Recently, three-dimensional chromatin has emerged as an important transcriptional control mechanism. For example, enhancers were shown regulate target genes by physically interacting with them regardless their linear distance even if located on different...
Although genetic or epigenetic alterations have been shown to affect the three-dimensional organization of genomes, utility chromatin conformation in classification human disease has never addressed.Here, we explore whether can be used classify leukemia. We map HOXA gene cluster a panel cell lines with 5C chromosome capture technology, and use data train test support vector machine classifier named 3D-SP. show that 3D-SP is able accurately distinguish leukemias expressing MLL-fusion proteins...
Abstract While DNA N 6 -adenine methylation (6mA) is best known in prokaryotes, its presence eukaryotes has generated great interest recently. Biochemical and genetic evidence supports that AMT1, a MT-A70 family methyltransferase (MTase), crucial for 6mA deposition unicellular eukaryotes. Nonetheless, transmission mechanism remains to be elucidated. Taking advantage of Single Molecule Real-Time Circular Consensus Sequencing (SMRT CCS), here we provide definitive semi-conservative 6mA,...
Mutations in the adult β-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and β-thalassemia. An increase fetal hemoglobin expression throughout adulthood, condition named hereditary persistence (HPFH), has been found ameliorate hemoglobinopathies. Deletional HPFH occurs through excision significant portion 3′ end locus, CTCF binding site termed 3′HS1. Here, we show that deletion this alone induces both CD34+ hematopoietic stem progenitor cells HUDEP-2...
Abstract Proper gene regulation is crucial for cellular differentiation, and dysregulation of key genes can lead to diseased states such as cancer. The HOX transcription factors play a role during hematopoiesis, aberrant expression certain HOXA found in acute myeloid leukemias (AMLs). While studies have shown that these are targeted by variety mutant proteins including NPM1, MLL fusions, NUP98 little known about how long-range 3D chromatin interactions regulate the normal hematopoiesis...
Understanding how transcription occurs requires the integration of genome-wide and locus-specific information gleaned from robust technologies. Chromatin immunoprecipitation (ChIP) is a staple in gene expression studies, while methods are available, high-throughput approaches to analyze defined regions lacking. Here, we present carbon copy-ChIP (2C-ChIP), versatile, inexpensive, technique quantitatively measure abundance DNA sequences ChIP samples. This method combines with ligation-mediated...
Abstract Objective Ligation-Mediated Amplification (LMA) is a versatile biochemical tool for amplifying selected DNA sequences. LMA has increased in popularity due to its integration within chromosome conformation capture (5C) and chromatin immunoprecipitation (2C-ChIP) methodologies. The output of either 5C or 2C-ChIP protocols single-read sequencing library ligated primer pairs that may not be multiplexed. While many computational tools currently exist read mapping analysis, these neither...