A5062479793- RNA modifications and cancer
- RNA Research and Splicing
- Melanoma and MAPK Pathways
- RNA and protein synthesis mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Hippo pathway signaling and YAP/TAZ
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- Cutaneous Melanoma Detection and Management
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Wnt/β-catenin signaling in development and cancer
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Computational Drug Discovery Methods
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Nutrition, Genetics, and Disease
- Prostate Cancer Diagnosis and Treatment
- Urologic and reproductive health conditions
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Pancreatic and Hepatic Oncology Research
- Single-cell and spatial transcriptomics
McGill University
2017-2022
McGill Genome Centre
2021-2022
McGill University Health Centre
2020-2022
McGill University and Génome Québec Innovation Centre
2022
Ontario Institute for Cancer Research
2016-2017
Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors mutation burden compared other cancers and, as result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between stroma, tumor cells, and distinct TIL subsets remains substantial challenge in oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types microenvironment...
Nuclear mutations are well known to drive tumor incidence, aggression and response therapy. By contrast, the frequency roles of in maternally inherited mitochondrial genome poorly understood. Here we sequence genomes 384 localized prostate cancer patients, identify a median one single-nucleotide variant (mtSNV) per patient. Some these mtSNVs occur recurrent mutational hotspots associate with aggressive disease. Younger patients have fewer than those who diagnosed at an older age. We...
Abstract The abundance of mRNA is mainly determined by the rates RNA transcription and decay. Here, we present a method for unbiased estimation differential decay rate from RNA-sequencing data modeling kinetics metabolism. We show that in all primary human tissues tested, particularly central nervous system, many pathways are regulated at stability level. parsimonious regulatory model consisting two RNA-binding proteins four microRNAs modulate landscape brain, which suggests new link between...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease where substantial heterogeneity in clinical presentation urgently requires better stratification of patients for the development drug trials and care. In this study we explored through crowdsourcing approach, DREAM Prize4Life ALS Stratification Challenge. Using data from >10,000 1479 community-based patient registers, more than 30 teams developed new approaches machine learning clustering, outperforming best current...
Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using statistical framework decouple transcriptional and effects RNA-seq data, we uncover stability changes that accompany tumour development progression. Analysis 7760 samples across 18 cancer types suggests are ~30% as frequent events, highlighting their widespread role shaping transcriptome. Dysregulation associated with >80 RNA-binding proteins (RBPs)...
Although combination BRAF/MEK inhibition has produced significant survival benefits for BRAF p.V600 mutant melanomas, targeted therapies approved non-p.V600 melanomas remain limited. Through the analysis of 772 cutaneous melanoma exomes, we reveal that mutations co-occurs more frequently with NF1 loss, but not oncogenic NRAS mutations, than expected by chance. We present cell signaling data, which demonstrate mutants can signal as monomers and dimers within an loss context. Concordantly,...
Abstract Background Melanoma-intrinsic activated β-catenin pathway, the product of catenin beta 1 ( CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about association between adenomatous polyposis coli (APC) CTNNB1 gene mutations stage IV immunotherapy response overall survival (OS). Methods We examined prognostic...
Cyclic AMP (cAMP) signaling is localized to multiple spatially distinct microdomains, but the role of cAMP microdomains in cancer cell biology poorly understood. Here, we present a tunable genetic system that allows us activate specific microdomains. We uncover nuclear microdomain activates tumor-suppressive pathway broad range cancers by inhibiting YAP, key effector protein Hippo pathway, inside nucleus. show induces LATS-dependent leading phosphorylation YAP solely at serine 397 and export...
Abstract RNA stability is a crucial and often overlooked determinant of gene expression. Some the regulators mRNA are long known as key oncogenic or tumour suppressor factors. Nonetheless, extent to which contributes transcriptome remodeling in cancer unknown, factors that modulate during development progression largely uncharacterized. Here, by decoupling transcriptional post-transcriptional effects RNA-seq data 7760 samples from 18 types, we present pan-cancer view changes accompany...
Summary cAMP signaling pathways are critical for both oncogenesis and tumor suppression. is localized to multiple spatially distinct microdomains, but the role of microdomains in cancer cell biology poorly understood. We developed a tunable genetic system that allows us activate specific microdomains. uncovered previously unappreciated nuclear microdomain functionally activates suppressive pathway broad range cancers by inhibiting YAP, key effector protein Hippo pathway, inside nucleus. show...