Samuel Aparicio

Distinguished Scientist, Department Head
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Dr. Samuel Aparicio (BM, BCh, PhD, FRCPath, FRSC) is the Nan & Lorraine Robertson Chair in Breast Cancer Research, holds the Canada Research Chair (Tier 1) in Molecular Oncology, and is the recipient of the 2014 Aubrey J Tingle Prize. He is also Head of the Department of Breast and Molecular Oncology at BC Cancer Research, part of the Provincial Health Services Authority, and a Professor in the Department of Pathology and Laboratory Medicine at UBC.

Dr. Aparicio graduated in medical and natural sciences from Cambridge University (UK), clinical medicine from Oxford, and subsequently in internal medicine and pathology. After doctoral work with Sydney Brenner in Cambridge, he held a Wellcome Trust Career Development Fellowship at the Wellcome/CRUK Developmental Biology Institute. From 2000-2005 he was a senior investigator in the Department of Oncology, Cambridge. He was a co-leader of the international consortium that sequenced the genome of the pufferfish Fugu rubripes in 2002. He moved to Vancouver in 2005.

Dr. Aparicio’s research program encompasses the fields of cancer genomics, mouse genetic models, high throughput screens, small molecule chemical probes and translational breast cancer research. His most recent work on the molecular taxonomy of breast cancer led to identification of new genes that could change the way breast cancer is diagnosed, and form the basis of next-generation treatments. This discovery was preceded by another breakthrough in decoding the genetic makeup of the most-deadly form of breast cancer, known as triple negative subtype. Dr. Aparicio is also working to develop quantitative measures of clonal fitness in patients, including methods for single cell genome sequencing and PDX models of human cancer. He collaborates widely with other groups, with current projects including the genomic and biochemical analysis of lymphoma, ovarian cancer, and several rare pediatric cancers. He was a co-founder of Paradigm Therapeutics (now, Takeda Cambridge) and currently Contextual Genomics Ltd. He was elected to the Royal Society of Canada in 2016 and is honoured as a University of British Columbia Distinguished University Scholar (2017). His contributions to academic research have been widely published in scientific and clinical journals such as Nature, Science, Cell and the New England Journal of Medicine. He is the recipient of numerous awards from academic as well as industrial institutions.

Other affiliations:
Faculty member, UBC Genome Science and Technology Graduate Program
Associate member, UBC Department of Medical Genetics
Associate member, UBC CIHR/MSFHR Bioinformatics Program
Associate member, Michael Smith Genome Sciences Centre

Credentials:
Professor, Department of Pathology and Laboratory Medicine, University of British Columbia
Canada Research Chair in Molecular Oncology
Department Head, BC Cancer, Department of Molecular Oncology
Nan & Lorraine Robertson Chair of Breast Cancer Research, UBC/BC Cancer
Associate Member, University of British Columbia, CIHR/MSFHR Bioinformatics Program
Associate Member, BC Cancer, Genome Sciences Center
Affiliated Investigator, Vancouver Coastal Health Authority
Distinguished Scientist, BC Cancer, Department of Molecular Oncology
PhD, University of Cambridge

Papers

DNA methylation landscapes of 1538 breast cancers reveal a replication-linked clock, epigenomic instability and cis-regulation.

Clonal fitness inferred from time-series modelling of single-cell cancer genomes.

A Scalable Strand-Specific Protocol Enabling Full-Length Total RNA Sequencing From Single Cells.

Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461.

Epiclomal: Probabilistic clustering of sparse single-cell DNA methylation data.

Higher serum PD-L1 level predicts increased overall survival with lapatinib versus trastuzumab in the CCTG MA.31 phase 3 trial.

Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumors.

Age-correlated protein and transcript expression in breast cancer and normal breast tissues is dominated by host endocrine effects

Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer

Eleven grand challenges in single-cell data science.

Identification of a selective DDX3X inhibitor with newly developed quantitative high-throughput RNA helicase assays.

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses.

Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling.

Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation.

Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups.

clonealign: statistical integration of independent single-cell RNA and DNA sequencing data from human cancers.

Decoding Transcriptome Dynamics of Genome-Encoded Polyadenylation and Autoregulation with Small-Molecule Modulators of Alternative Polyadenylation.

High-Resolution Single-Cell DNA Methylation Measurements Reveal Epigenetically Distinct Hematopoietic Stem Cell Subpopulations.

Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors.

Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.

Engineered in-vitro cell line mixtures and robust evaluation of computational methods for clonal decomposition and longitudinal dynamics in cancer.

Impact of serum HER2, TIMP-1, and CAIX on outcome for HER2+ metastatic breast cancer patients: CCTG MA.31 (lapatinib vs. trastuzumab).

Discovery and Characterization of a Eukaryotic Initiation Factor 4A-3-Selective Inhibitor That Suppresses Nonsense-Mediated mRNA Decay.

Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes.

Discovery of Novel 1,4-Diacylpiperazines as Selective and Cell-Active eIF4A3 Inhibitors.

CDK12 regulates alternative last exon mRNA splicing and promotes breast cancer cell invasion.

Atrophin controls developmental signaling pathways via interactions with Trithorax-like.

Discovery of selective ATP-competitive eIF4A3 inhibitors.

ddClone: joint statistical inference of clonal populations from single cell and bulk tumour sequencing data.

CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor.

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours.

Scalable whole-genome single-cell library preparation without preamplification.

Patient-derived xenograft (PDX) models in basic and translational breast cancer research.

The RNA helicase DDX39B and its paralog DDX39A regulate androgen receptor splice variant AR-V7 generation.

Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks.

A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.

Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer.

Robust high-performance nanoliter-volume single-cell multiple displacement amplification on planar substrates.

Bimolecular complementation affinity purification (BiCAP) reveals dimer-specific protein interactions for ERBB2 dimers.

Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer.

Corrigendum: Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.

Clonal genotype and population structure inference from single-cell tumor sequencing.

Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.

The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes.

Lessons learned from the application of whole-genome analysis to the treatment of patients with advanced cancers.

Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro.

Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells.

Systematic analysis of somatic mutations impacting gene expression in 12 tumour types.

Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.

Examining the utility of patient-derived xenograft mouse models.

Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31.

A co-culture genome-wide RNAi screen with mammary epithelial cells reveals transmembrane signals required for growth and differentiation.

DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts.

In vivo radioimaging of bradykinin receptor b1, a widely overexpressed molecule in human cancer.

Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution.

Tumor heterogeneity: next-generation sequencing enhances the view from the pathologist's microscope.

A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer.

Genome-driven integrated classification of breast cancer validated in over 7,500 samples.

TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data.

Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.

Insulin-like peptide 5 is an orexigenic gastrointestinal hormone.

Impact of MLL5 expression on decitabine efficacy and DNA methylation in acute myeloid leukemia.

TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance.

A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis.

The Breast Cancer Oncogene EMSY Represses Transcription of Antimetastatic microRNA miR-31.

PyClone: statistical inference of clonal population structure in cancer.

The breast cancer oncogene EMSY represses transcription of antimetastatic microRNA miR-31.

Clonal analysis via barcoding reveals diverse growth and differentiation of transplanted mouse and human mammary stem cells.

The omics of triple-negative breast cancers.

Solution NMR structure and histone binding of the PHD domain of human MLL5.

Signatures of mutational processes in human cancer.

TDP1 and PARP1 deficiency are cytotoxic to rhabdomyosarcoma cells.

Improving breast cancer survival analysis through competition-based multidimensional modeling.

Systematic analysis of challenge-driven improvements in molecular prognostic models for breast cancer.

The implications of clonal genome evolution for cancer medicine.

A new genome-driven integrated classification of breast cancer and its implications.

DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer.

A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through MAPK activation.

The landscape of cancer genes and mutational processes in breast cancer.

Integrative analysis of genome-wide loss of heterozygosity and monoallelic expression at nucleotide resolution reveals disrupted pathways in triple-negative breast cancer.

Mutational processes molding the genomes of 21 breast cancers.

The life history of 21 breast cancers.

PPM1H is a p27 phosphatase implicated in trastuzumab resistance.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

The clonal and mutational evolution spectrum of primary triple-negative breast cancers.

Opening Pandora's Box--the new biology of driver mutations and clonal evolution in cancer as revealed by next generation sequencing.

JointSNVMix: a probabilistic model for accurate detection of somatic mutations in normal/tumour paired next-generation sequencing data.

Molecular alterations between the primary breast cancer and the subsequent locoregional/metastatic tumor.

Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers.

Feature-based classifiers for somatic mutation detection in tumour-normal paired sequencing data.

Mll5 is required for normal spermatogenesis.

Nucleic acid quantity and quality from paraffin blocks: defining optimal fixation, processing and DNA/RNA extraction techniques.

Raman microscopy-based cytochemical investigations of potential niche-forming inhomogeneities present in human embryonic stem cell colonies.

High-throughput microfluidic single-cell RT-qPCR.

Absolute quantification of intracellular glycogen content in human embryonic stem cells with Raman microspectroscopy.

Retinoblastoma-binding proteins 4 and 9 are important for human pluripotent stem cell maintenance.

Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.

The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent.

ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium.

Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation.

The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse.

Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas.

ARID1A mutations in endometriosis-associated ovarian carcinomas.

P-cadherin expression as a prognostic biomarker in a 3992 case tissue microarray series of breast cancer.

Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development.

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.

Human mammary cancer progression model recapitulates methylation events associated with breast premalignancy.

Does massively parallel DNA resequencing signify the end of histopathology as we know it?

Evolutionary concepts in biobanking - the BC BioLibrary.

Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution.

p53: a new kingpin in the stem cell arena.

Mutation of FOXL2 in granulosa-cell tumors of the ovary.

Inter-observer reproducibility of HER2 immunohistochemical assessment and concordance with fluorescent in situ hybridization (FISH): pathologist assessment compared to quantitative image analysis.

A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability.

A loss of function allele for murine Staufen1 leads to impairment of dendritic Staufen1-RNP delivery and dendritic spine morphogenesis.

Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation.

Intensity calibration and automated cell cycle gating for high-throughput image-based siRNA screens of mammalian cells.

Transcriptome analysis of the normal human mammary cell commitment and differentiation process.

Columnar cell lesions, mammographic density and breast cancer risk.

Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?

Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma.

Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy.

Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.

Kisspeptins and GPR54--the new biology of the mammalian GnRH axis.

PEDF and the serpins: phylogeny, sequence conservation, and functional domains.

Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.

Genetic approaches to unraveling G protein-coupled receptor biology.

p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels.

Fugu genome analysis provides evidence for a whole-genome duplication early during the evolution of ray-finned fishes.

Expression microarray reproducibility is improved by optimising purification steps in RNA amplification and labelling.

EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer.

The GPR54 gene as a regulator of puberty.

Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes.

The molecular outlook.