A5059491088- Cancer-related Molecular Pathways
- Collagen: Extraction and Characterization
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Meat and Animal Product Quality
- Genomic variations and chromosomal abnormalities
- Microtubule and mitosis dynamics
- Genetic factors in colorectal cancer
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Connective tissue disorders research
- Erythrocyte Function and Pathophysiology
- Sarcoma Diagnosis and Treatment
- Virus-based gene therapy research
- Protease and Inhibitor Mechanisms
- Ocular Oncology and Treatments
- Tendon Structure and Treatment
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Cardiac Valve Diseases and Treatments
- Bone Tissue Engineering Materials
- Cancer therapeutics and mechanisms
- Dermatological and Skeletal Disorders
University of Toronto
2017-2024
Hospital for Sick Children
2017-2023
SickKids Foundation
2022
McGill University and Génome Québec Innovation Centre
2014
McGill University
2011-2013
Johnson & Johnson (United Kingdom)
1991-2002
Devro (United Kingdom)
1989
Biotechnology and Biological Sciences Research Council
1980-1987
Guy's Hospital
1985
At Bristol
1985
Abstract Gains and losses of DNA are prevalent in cancer emerge as a consequence inter-related processes replication stress, mitotic errors, spindle multipolarity breakage–fusion–bridge cycles, among others, which may lead to chromosomal instability aneuploidy 1,2 . These copy number alterations contribute initiation, progression therapeutic resistance 3–5 Here we present conceptual framework examine the patterns human that is widely applicable diverse data types, including whole-genome...
We conducted integrative somatic-germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children adolescents/young adults with cancer of poor prognosis or rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified 56% patients. Improved diagnostic accuracy led to modified management a subset. Therapeutically targetable (54% patients) unanticipated...
The content of type I and III collagen in normal human skin from subjects different ages was studied by means a new high performance liquid chromatography method SDS-polyacrylamide gel electrophoresis scanning electron microscopy. ratio types covered remained constant throughout childhood young adult life the proportion shown to be same as previously reported. However, elderly, dermis increased variable degree. Scanning microscopic examination showed decrease number fibre bundles with age....
In the past it has been proven difficult to separate and characterize collagen from muscle because of its relative paucity in this tissue. The present report presents a comprehensive methodology, combining methods previously described by McCollester [(1962) Biochim. Biophys. Acta 57, 427-437] Laurent, Cockerill, McAnulty & Hastings [(1981) Anal. Biochem. 113, 301-312], which three major tracts connective tissue, epimysium, perimysium endomysium, may be prepared separated bulk protein....
Rabbit forelimb tendons incubated for 15 or 21 days at 35 degrees C in the presence of 8 24 mg glucose/ml were shown to change their chemical, biochemical and mechanical characteristics. The treated with glucose contained up three times as much hexosyl-lysine hexosylhydroxylysine did control judged by assay NaB3H4-reduced samples. Measurement force generated on thermal contraction showed significant increases glycosylated compared controls, indicating formation new covalent stabilizing...
Abstract Background X-chromosome inactivation (XCI) results in the silencing of most genes on one X chromosome, yielding mono-allelic expression individual cells. However, random XCI both alleles females. Allelic imbalances have been used genome-wide to detect mono-allelically expressed genes. Analysis X-linked allelic imbalance females with skewed offers opportunity identify that escape bi-allelic contrast those and which are therefore subject XCI. Results We determine status for 409 genes,...
Although replication repair deficiency, either by mismatch deficiency (MMRD) and/or loss of DNA polymerase proofreading, can cause hypermutation in cancer, microsatellite instability (MSI) is considered a hallmark MMRD alone. By genome-wide analysis tumors with germline and somatic deficiencies repair, we reveal novel association between proofreading MSI, especially when both components are lost. Analysis indels microsatellites (MS-indels) identified five distinct signatures (MS-sigs)....
Abstract Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well mutational signatures prior chemotherapy. identify near-ubiquitous early loss heterozygosity , gain the mutant allele. This occurs earlier in these compared to...
Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors subtype, origins, timing unknown. Here we analyze 70 genomes 130 transcriptomes LMS, including multiple tumor regions paired metastases. Molecular profiling highlight very early origins...
The reconstitution of glucocerebrosidase activity from its inactive macromolecular components depended on acidic membrane phospholipids.
Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all cancer. In this study, we investigated germline sequence structural variation in a broad set genes two large, independent RMS cohorts.
The conversion of the reducible divalent cross-links in collagen to non-reducible multivalent mature has resulted identification several new amino acids as putative cross-link. None these compounds completely satisfied necessary criteria. We have now isolated an acid high Mr, derived from lysine, that is only present high-Mr peptides collagen. Its increase with age tissue correlates decrease cross-links, and it both skin bone, which are initially cross-linked through aldimine oxo-imine...
Mitral valve prolapse was sought clinically and with phonocardiography M mode sector echocardiography in 15 women aged 22-57 years joint hypermobility syndrome. The type III:III + I collagen ratio measured skin biopsy specimens found to be raised seven of 10 patients sampled. Thirteen had increased aortic wall compliance by the continuous wave Doppler ultrasound technique. Ten (67%) mitral shown auscultatory signs or both--a prevalence at least three times greater than that general adult...