A5103069107- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Lung Cancer Research Studies
- Prostate Cancer Treatment and Research
- RNA Research and Splicing
- Pancreatic and Hepatic Oncology Research
- Advanced Biosensing Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Neuroendocrine Tumor Research Advances
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- T-cell and B-cell Immunology
- Glioma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Cell death mechanisms and regulation
- Genomics and Chromatin Dynamics
- Cancer Research and Treatments
- Cancer-related molecular mechanisms research
- Brain Metastases and Treatment
- Sexual Differentiation and Disorders
- Acute Myeloid Leukemia Research
- Hedgehog Signaling Pathway Studies
- Immune Cell Function and Interaction
University Health Network
2013-2024
Princess Margaret Cancer Centre
2013-2024
University of Toronto
2020-2022
Wilfrid Laurier University
2022
Ontario Institute for Cancer Research
2022
Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation antiandrogens, which enabled transcriptional silencing REs otherwise stimulate signaling and glucocorticoid receptor...
Abstract Background Resolving the differential diagnosis between brain metastases (BM), glioblastomas (GBM), and central nervous system lymphomas (CNSL) is an important dilemma for clinical management of main three intra-axial tumor types. Currently, treatment decisions require invasive diagnostic surgical biopsies that carry risks morbidity. This study aimed to utilize methylomes from cerebrospinal fluid (CSF), a biofluid proximal tumors, reliable non-invasive classification addresses...
Abstract In embryonic stem cells, promoters of key lineage-specific differentiation genes are found in a bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for transcription upon loss H3K27me3. Whether cancer-initiating cells (C-ICs) have similar epigenetic mechanisms that prevent lineage commitment is unknown. Here we show colorectal C-ICs (CC-ICs) maintained stem-like state through mechanism. Disruption the inhibition H3K27...
Abstract Hematopoietic stem cell (HSC) dormancy is understood as supportive of HSC function and its long-term integrity. Although regulation stress responses incurred a result activation recognized important in maintaining function, little the preventive machinery present human HSCs that may serve to resist their promote self-renewal. We demonstrate transcription factor PLAG1 essential for and, when overexpressed, endows 15.6-fold enhancement frequency functional stimulatory conditions....
Aim: We examined methylation changes in cell-free DNA (cfDNA) metastatic castration-resistant prostate cancer (mCRPC) during treatment. Patients & methods: Genome-wide analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Results: Alterations states genes previously implicated progression were observed and that maintained throughout tended to have a longer time clinical progression. Importantly, we also report...
Functional genomic screens in two-dimensional cell culture models are limited identifying therapeutic targets that influence the tumor microenvironment. By comparing targeted CRISPR-Cas9 a with xenografts derived from same line, we identified MEN1 as top hit confers differential dropout effects vitro and vivo. knockout multiple solid cancer types does not impact proliferation but significantly promotes or inhibits growth immunodeficient immunocompetent mice, respectively. Mechanistically,...
Abstract Limited studies to date have investigated the detectability of cell-free DNA (cfDNA) markers in asymptomatic individuals prior a cancer diagnosis. Here, we performed cfDNA methylation profiling blood up seven years breast diagnosis addition matched cancer-free controls (n=150). We identified differentially methylated signatures that discriminated from pre-diagnosis cases over five and demonstrate these were reflective profiles tissue. report classification range detected at Stage I...
Abstract Cell-free DNA (cfDNA) epigenetic and fragmentomic profiling has emerged as prominent non-invasive approaches for early cancer detection subtyping. However, owing to difficulties in observing the development of human malignancies, most biomarker evolution studies date have primarily examined biologics following a diagnosis. Utilizing cfDNA screening tool disease requires assessment blood plasma samples collected from asymptomatic individuals prior diagnosis cancers. Here, we leverage...
Abstract Introduction Small cell lung cancer (SCLC) is a highly aggressive type of with high risk recurrence. The SCLC methylome may yield biologic insight but understudied due to difficulty in acquiring primary patient tissue. Here, we comprehensively profile the using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq). Methods cfDNA was extracted from plasma samples collected 74 patients prior initiation first-line treatment and 20 non-cancer smoker participants. Genomic...
Abstract Cancer survival rates are significantly improved when detected at early stages, particularly the tumour is still localised to tissue of origin. However, effective screening tools for cancer detection currently limited a subset types. Profiling cell-free DNA (cfDNA) patterns has emerged as prominent non-invasive biomarker and subtyping cancers. owing difficulties in observing development human malignancies cancers often once they become symptomatic, most evolution studies date have...
Abstract Glioblastoma is a highly malignant tumour driven by subset of self-renewing cells termed glioblastoma stem cells. This self-renewal phenotype largely epigenetically driven, however, the exact epigenetic mechanisms underpinning it are poorly understood. We found that histone variant macroH2A2 repressed in tumours, and this repression associated with poorer survival. interrogate function using vitro vivo patient-derived models. show antagonizes expression NPC OPC-like markers, rewires...
Abstract Cancer survival rates are significantly improved when detected at early stages, particularly the tumor is still localized to tissue of origin. However, effective screening tools for cancer detection currently limited a subset types. The development human malignancies difficult observe as cancers often once it becomes symptomatic, such many biomarker and evolution studies date have primarily examined genomics from solid or liquid biopsies following diagnosis. Investigating in...
SUMMARY Gene expression profiling and proteome analysis of normal malignant hematopoietic stem cells (HSC) point to shared core stemness properties. However, discordance between mRNA protein signatures underscores an important role for post-transcriptional regulation by miRNAs in governing this critical nexus. Here, we identified miR-130a as a regulator HSC self-renewal differentiation. Enforced impaired B lymphoid differentiation expanded long-term HSC. Integration mass spectrometry...