A5025976605- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Mathematical and Theoretical Epidemiology and Ecology Models
- RNA regulation and disease
- Ferroptosis and cancer prognosis
- Cancer Cells and Metastasis
- Health Systems, Economic Evaluations, Quality of Life
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Computational Drug Discovery Methods
- Animal Behavior and Reproduction
- Pharmaceutical Economics and Policy
- Evolution and Genetic Dynamics
University of Toronto
2017-2022
Lunenfeld-Tanenbaum Research Institute
2017-2022
Mount Sinai Hospital
2019-2022
Sinai Hospital
2022
Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater of isocitrate dehydrogenase (
A leading hypothesis for the evolutionary maintenance of sexual reproduction proposes that sex is advantageous because it facilitates adaptation. Changes in environment stimulate adaptation but not all changes are equivalent; a change may occur along one or multiple environmental dimensions. In two evolution experiments with facultatively rotifer Brachionus calyciflorus, we test how complexity affects by adapting replicate populations to various environments differ from original one, two,...
Abstract CRISPR-Cas9 is an efficient and versatile tool for genome engineering in many species. However, inducible editing systems that regulate Cas9 activity or sgRNA expression often suffer from significant limitations, including reduced capacity, off-target effects, leaky expression. Here, we develop a precisely controlled cassette can be combined with widely-used Cre systems, termed CRISPR-Switch (SgRNA With Induction/Termination by Homologous recombination). Switch-ON facilitates...
Abstract Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single nucleotide polymorphism rs55705857 (A>G), which confers a 6-fold increased of IDH-mutant low-grade glioma (LGG) amongst highest genetic associations with cancer. By fine-mapping locus, reveal that itself variant associated molecular pathways drive LGG. Mechanistically, show resides within brain-specific enhancer, where allele disrupts OCT2/4 binding, allowing...
Abstract BACKGROUND The topologically associated domain (TAD) on 8q24 surrounding MYC is important for many types of cancer. region also in the formation IDH-mutant glioma; risk allele rs55705857 being with development these tumors. significantly increased tumors an mouse model. Cerebral organoids have been found to recapitulate early brain. We hypothesized that may alter phenotype cerebral organoids. METHODS Isogenic induced pluripotent stem cells (iPSCs) were developed (n=3) and without...
Abstract BACKGROUND Determination of the causation germline single nucleotide polymorphisms (SNPs) located in non-coding regions genome is challenging. The genomic region 8q24 has been identified as important many kinds cancer, linked to a topologically associated domain (TAD) encompassing MYC; this TAD contains GWAS SNP (rs55705857) with IDH-mutant glioma. METHODS Germline genotyping data from 622 glioma and 668 controls were used fine map rs55705857 locus by detailed haplotype analysis....
Abstract Low-grade glioma (LGG) are generally slowly growing brain cancers, that frequently undergo malignant progression to aggressive, secondary glioblastoma with a dismal prognosis. By combining genetically engineered Idh1-mutant mice in vivo CRISPR gene editing we generated mouse model faithfully recapitulating the founder mutations of LGG. Clonal activation neomorphic Idh1 R132H mutation cooperates Trp53 and Atrx trigger development tumors but only ~30% penetrance very long latency. To...
Abstract Establishing causal links between genetic polymorphisms and increased heritable risk of developing brain cancer is a major challenge. The non-coding single nucleotide polymorphism rs55705857 (A >G) associated with ~6-fold to develop IDH-mutant low-grade glioma (LGG). G allele has minor frequency only ~5% in the general population but found ~40% patients LGG carrying risk-alleles are diagnosed on average 7-12 years earlier than those non-risk A alleles. This makes one highest...