A5054284916- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Ovarian cancer diagnosis and treatment
- Cancer-related Molecular Pathways
- Ocular Oncology and Treatments
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Immunodeficiency and Autoimmune Disorders
- Genomic variations and chromosomal abnormalities
- Advanced biosensing and bioanalysis techniques
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Gastric Cancer Management and Outcomes
- Single-cell and spatial transcriptomics
- Lung Cancer Research Studies
- Nanopore and Nanochannel Transport Studies
- Protist diversity and phylogeny
- Radiomics and Machine Learning in Medical Imaging
- Chronic Lymphocytic Leukemia Research
- Fish Biology and Ecology Studies
Ontario Institute for Cancer Research
2017-2024
Princess Margaret Cancer Centre
2021
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
2021
Istituti di Ricovero e Cura a Carattere Scientifico
2021
Institute of Cancer Research
2020
Cancer Research Institute
2018
Health Net
2018
University of Toronto
2005-2017
Donnelly College
2012
<ns4:p>Haplotypes are often critical for the interpretation of genetic laboratory observations into medically actionable findings. Current massively parallel DNA sequencing technologies produce short sequence reads that unable to resolve haplotype information. Phasing read data typically requires supplemental statistical phasing based on known structure in population or parental genotypic data. Here we demonstrate MinION nanopore sequencer is capable producing very long both variants and...
People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for range clinical applications, including early cancer detection. Here, we provide proof-of-principle multimodal liquid assay that integrates targeted gene panel, shallow whole-genome, cell-free methylated DNA immunoprecipitation sequencing...
Abstract Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing matched tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated immunoprecipitation (cfMeDIP-seq) 204 samples from 87 patients before during treatment with a pan-cancer phase II investigator-initiated trial (INSPIRE). trained signature independent array data The Cancer Genome Atlas quantify...
The evolution of drug resistance in fungal pathogens compromises the efficacy limited number antifungal drugs. Drug combinations have emerged as a powerful strategy to enhance and abrogate resistance, but impact on remains largely unexplored. Targeting molecular chaperone Hsp90 or its downstream effector, protein phosphatase calcineurin, abrogates most widely deployed antifungals, azoles, which inhibit ergosterol biosynthesis. Here, we evolved experimental populations model yeast...
The eukaryotic nucleosome is the fundamental unit of chromatin, comprising a protein octamer that wraps ∼147 bp DNA and has essential roles in compaction, replication gene expression. Nucleosomes chromatin have historically been considered to be unique eukaryotes, yet studies select archaea identified homologs histone proteins assemble into tetrameric nucleosomes. Here we report first archaeal genome-wide occupancy map, as observed halophile Haloferax volcanii. Nucleosome was compared with...
To evaluate the use of blood cell-free DNA (cfDNA) to identify emerging mechanisms resistance PARP inhibitors (PARPi) in high-grade serous ovarian cancer (HGSOC).
An effective tool for the global analysis of both DNA methylation status and protein–chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type array suited this purpose takes advantage strong association between CpG Islands (CGIs) gene regions. We have obtained 20 736 clones from CGI Library used these to construct arrays. The utility library requires proper annotation assessment clones, including content, genomic origin proximity neighboring...
Haplotypes are often critical for the interpretation of genetic laboratory observations into medically actionable findings. Current massively parallel DNA sequencing technologies produce short sequence reads that unable to resolve haplotype information. Phasing read data typically requires supplemental statistical phasing based on known structure in population or parental genotypic data. Here we demonstrate MinION nanopore sequencer is capable producing very long both variants and haplotypes...
Background Sitravatinib, a tyrosine kinase inhibitor that targets TYRO3, AXL, MERTK and the VEGF receptor family, is predicted to increase M1 M2-polarized tumor-associated macrophages ratio in tumor microenvironment have synergistic antitumor activity combination with anti-programmed death-1/ligand-1 agents. SNOW window-of-opportunity study designed evaluate immune molecular effects of preoperative sitravatinib nivolumab patients oral cavity squamous cell carcinoma. Methods Patients...
Abstract Background Both genetic and methylation analysis have been shown to provide insight into the diagnosis prognosis of many brain tumors. However, implication profiling its interaction with alterations in pediatric low-grade gliomas (PLGGs) are unclear. Methods We performed a comprehensive PLGG long-term clinical follow-up. In total 152 PLGGs were analyzed from range pathological subtypes, including 40 gangliogliomas. Complete molecular was compared genome-wide data outcome all...
Target identification is a critical step in the lengthy and expensive process of drug development. Here, we describe genome-wide screening platform that uses systematic overexpression pooled human ORFs to understand mode-of-action resistance mechanisms. We first calibrated our screen with well-characterized methotrexate. then identified new genes involved bioactivity diverse drugs including antineoplastic agents biologically active molecules. Finally, focused on transcription factor RHOXF2...
Uveal melanomas are rare tumors arising from melanocytes that reside in the eye. Despite surgical or radiation treatment, approximately 50% of patients with uveal melanoma will progress to metastatic disease, most often liver. Cell-free DNA (cfDNA) sequencing is a promising technology due minimally invasive sample collection and ability infer multiple aspects tumor response. We analyzed 46 serial cfDNA samples 11 over 1-year period following enucleation brachytherapy (n = ∼4/patient) using...
Abstract Background In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum‐based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups chemotherapy responders (good vs. poor). Methods Following primary debulking surgery and intravenous carboplatin/paclitaxel, women with stage III–IV were grouped by response. Patients in the good response (GR) poor (PR) respectively had progression‐free intervals (PFI) ≥12 ≤6...
The correlation between blood-based tumor mutation burden (bTMB) and tissue-based burden(tTMB) has not been broadly tested in a multicancer cohort. Here, we assess the bTMB with tTMB phase I trial patients treated immunotherapy. As an exploratory analysis, evaluated circulating DNA (ctDNA) dynamics responders.
Summary Despite advances in cancer therapeutics, early detection is often the best prognostic indicator for survival ( 1 ). People with Li-Fraumeni syndrome harbor a germline pathogenic variant tumor suppressor gene TP53 2 ) and face near 100% lifetime risk of developing wide spectrum of, multiple, cancers 3 mutation carriers routinely undergo intensive surveillance protocols which, although associated significantly improved survival, are burdensome to both patient health care system 4...
2542 Background: Limited data exist in the clonal dynamics of serial ctDNA as a predictive biomarker advanced solid tumor pts receiving immune checkpoint blockade. Methods: Pts with mixed tumors received single agent P (anti-PD-1) 200 mg IV Q3wks investigator-initiated phase II INSPIRE trial (NCT02644369). was assayed at baseline (B) and start cycle 3 (C3) using pt-specific amplicon-based NGS assay (Signatera™). Samples were considered positive if ≥2 16 targets met qualifying confidence...
The application of new proteomics and genomics technologies support a view in which few drugs act solely by inhibiting single cellular target. Indeed, drug activity is modulated complex, often incompletely understood mechanisms. Therefore, efforts to decipher mode action through genetic perturbation such as RNAi typically yields "hits" that fall into several categories. Of particular interest the present study, we aimed characterize secondary activities on cells. Inhibiting known target can...
Abstract The phenotypic, geographic, and species diversity of cichlid fishes have made them a group great interest for studying evolutionary processes. Here we present targeted-exon next-generation sequencing approach investigating the relationships (Cichlidae), with focus on Neotropical subfamily Cichlinae using set 923 primarily single-copy exons designed through mining Nile tilapia ( Oreochromis niloticus ) genome. Sequence capture assembly were robust, leading to complete dataset 415 139...
2550 Background: Bespoke mutation-based circulating tumor DNA (ctDNA) predicts response to P but relies on availability of tissue and presence mutations. Cell-free methylated immunoprecipitation high-throughput sequencing (cfMeDIP-seq) may overcome these limitations be applied more pts. Methods: Pts with mixed solid tumors divided into 5 cohorts received 200 mg Q3wks in the investigator-initiated INSPIRE trial (NCT02644369). cfMeDIP-seq was performed at baseline (B), pre cycle 3 (C3) later...
5561 Background: Patients with advanced high grade serous ovarian cancer (SOC) who undergo a suboptimal debulking primary surgery typically have adverse clinical outcomes. However, spectrum of sensitivity to first line platinum-based chemotherapy is observed but poorly understood. In this study, we perform molecular characterization two groups responders (extreme versus poor) carboplatin/taxol in suboptimally debulked SOC patients. Methods: Suboptimally patients disease (stage III-IV) were...
<p>Figure S9 showing fragment length metrics in cfMeDIP libraries</p>