A5042596207- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomic variations and chromosomal abnormalities
- Cancer Immunotherapy and Biomarkers
- Genetics and Neurodevelopmental Disorders
- Computational Drug Discovery Methods
- Genetic factors in colorectal cancer
- Ferroptosis and cancer prognosis
- DNA Repair Mechanisms
- Genomics and Rare Diseases
- Telomeres, Telomerase, and Senescence
- Advanced Breast Cancer Therapies
- Bioinformatics and Genomic Networks
- Immune Cell Function and Interaction
- Sperm and Testicular Function
- Genetic Mapping and Diversity in Plants and Animals
- Single-cell and spatial transcriptomics
- Adrenal Hormones and Disorders
- Agriculture and Biological Studies
- Botanical Studies and Applications
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
Queen's University
2019-2024
University of British Columbia
2019-2022
British Columbia Children's Hospital
2019
Mosaic loss of Chromosome Y (LOY) is a common acquired structural mutation in the leukocytes aging men that correlated with several age-related diseases, including Alzheimer's disease (AD). The molecular basis LOY brain cells has not been systematically investigated. Here, we present large-scale analysis single-cell and single-nuclei RNA data sets, yielding 851,674 cells, to investigate cell type–specific burden LOY. frequencies differed widely between donors CNS types. Among five...
Abstract Background Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels transforming growth factor-β (TGF-β) ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour responses preclinical HGSC models. Methods BA is a first-in-class bifunctional inhibitor PD-L1, was tested for effects on overall survival altered TIME syngeneic Results Using mouse...
Although two-thirds of cancers arise from loss-of-function mutations in tumor suppressor genes, there are few approved targeted therapies linked to these alterations. Synthetic lethality offers a promising strategy treat such by targeting vulnerabilities unique cancer cells with mutations. To identify clinically relevant synthetic lethal interactions, we analyzed genome-wide CRISPR/Cas9 knock-out (KO) viability screens the Cancer Dependency Map and evaluated their clinical relevance patient...
Despite the recent availability of complete genome sequences tumors from thousands patients, isolating disease-causing (driver) non-coding mutations plethora somatic variants remains challenging, and only a handful validated examples exist. By integrating whole-genome sequencing, genetic data, allele-specific gene expression TCGA, we identified 320 that affect in cis (FDR<0.25). These cluster into 47 cis-regulatory elements modulate their subject genes through diverse molecular mechanisms....
Abstract Mosaic loss of chromosome Y (LOY) is a particularly common acquired structural mutation in the leukocytes aging men and it has been shown to correlate with several age-related diseases including Alzheimer’s disease (AD). To derive molecular basis LOY brain cells, we create an integrated resource by aggregating data from 21 single-cell single-nuclei RNA studies, yielding 763,410 cells investigate presence cell-type specific burden LOY. We created robust quantification metrics for...
<h3>Background</h3> Ovarian cancer is a leading cause of mortality in women due to late detection and lack durable therapy responses. The most aggressive subtype high grade serous ovarian (HGSC). Within the ascites, levels immunosuppressive cytokine Transforming Growth Factor-β (TGF-β) linked poor prognosis. We hypothesize that aberrant TGF-β signaling tumor microenvironment promotes resistance immunotherapies, including immune checkpoint inhibitors targeting PD-1/PD-L1. Here, we test...
Abstract Despite the recent availability of complete genome sequences tumors from thousands patients, isolating disease-causing (driver) non-coding mutations plethora somatic variants is notoriously challenging, and only a handful validated examples exist. By integrating whole-genome sequencing, gene expression, chromatin accessibility, genetic data TCGA, we identified 301 that affect expression in cis . These cluster into 36 hotspot regions with diverse molecular mechanisms regulation. We...
Abstract Cancer cell lines have numerous characteristics that make them favorable pre-clinical research models, yet they are notoriously poor at predicting drug response in the clinic. Here we sought to investigate utility of synthetic lethality (SL) interactions discovered from large-scale CRISPR functional screens (i.e. BROAD and Sanger Dependency Maps or "DepMap") as predictors targets validate patients. Mutual exclusivity, phenomenon where two genes rarely mutated together same tumor, is...
Fazit Die Studie hat gezeigt, dass ein gutes anfängliches Ansprechen auf eine Steroid-Injektion Langzeitergebnis erwarten lässt. Diese Patienten profitierten auch am besten von weiteren Injektionen, wenn die Symptome erneut auftraten. 62 % aller Studienteilnehmer benötigten keinen operativen Eingriff während des Untersuchungsjahres, weil Injektionen zumindest für diesen Zeitraum ausreichend Linderung schaffen konnten.
Identification of non-coding mutations driving tumorigenesis requires alternative approaches to coding mutations. Enriched associations between mutated regulatory elements and altered cis-regulation in tumors are a promising approach stratify candidate driver Here we provide bioinformatics pipeline mine data from the Cancer Genomic Commons (GDC) for such associations. The integrates RNA whole-genome sequencing with genotyping reveal putative by cancer type. For complete information on...