Wendy Greenwood
A5000849731- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Cell Image Analysis Techniques
- Health, Environment, Cognitive Aging
- TGF-β signaling in diseases
- Epigenetics and DNA Methylation
- Evolution and Genetic Dynamics
- Cancer-related Molecular Pathways
- Delphi Technique in Research
- Gene expression and cancer classification
- Sphingolipid Metabolism and Signaling
- Multiple Sclerosis Research Studies
- Research on Leishmaniasis Studies
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Advanced Fluorescence Microscopy Techniques
- Breast Cancer Treatment Studies
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- Ginseng Biological Effects and Applications
- Medical Imaging Techniques and Applications
University of Cambridge
2014-2024
Cancer Research UK Cambridge Center
2016-2023
IIT@MIT
2021
McGovern Institute for Brain Research
2021
Engineering Arts (United States)
2021
Allen Institute
2021
Howard Hughes Medical Institute
2021
Cancer Research UK
2012-2021
Breast Cancer Research Foundation
2016
The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection patient-derived tumor xenografts (PDTXs), which the morphological molecular characteristics originating are preserved through passaging mouse. An integrated platform combining vivo maintenance these PDTXs along with short-term cultures PDTX-derived cells (PDTCs) was optimized. Remarkably, genomic clonal architecture present cancers mostly upon...
Identifying transcript location in cells where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy allowed for better visualization of small structures expanding the tissues with polymer- hydrogel-based system. Alon et al. combined expansion long-read situ RNA sequencing, resulting more precise transcripts. This method, termed “ExSeq” was used to detect RNAs, both new transcripts those previously demonstrated localize...
Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, open source computational methods. Using we generated resource 51,926 matched cell images diverse types including lines, xenografts, diagnostic samples with limited...
Abstract A holistic understanding of tissue and organ structure function requires the detection molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous up to 40 antigens transcripts using metal-tagged antibodies but has so far been restricted two-dimensional imaging. Here we report development 3D IMC for multiplexed analysis at single-cell resolution demonstrate utility technology by human breast cancer samples. The resulting...
How cell-to-cell copy number alterations that underpin genomic instability
Abstract Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders classification frustrates therapy 1–3 . Consequently, spatially resolved omics-level analyses gaining traction 4–9 Despite considerable therapeutic interest, tumor metabolism has been lagging behind development there a paucity of data regarding its spatial organization. To address shortcoming, we set out to study the local metabolic effects oncogene c-MYC , pleiotropic...
Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, presence mouse stroma challenging for HTS data analysis. Indeed, high homology between two genomes results in a proportion reads being mapped human.
The heterogeneity of breast cancer plays a major role in drug response and resistance has been extensively characterized at the genomic level. Here, single-cell mass cytometry (BCMC) panel is optimized to identify cell phenotypes their oncogenic signalling states biobank patient-derived tumour xenograft (PDTX) models representing diversity human cancer. BCMC identifies 13 cellular (11 2 murine), associated with both subtypes specific features. Pre-treatment phenotypic composition determinant...
Summary: The Imaging and Molecular Annotation of Xenografts Tumors Cancer Grand Challenges team was set up with the objective developing “next generation” pathology cancer research by using a combination single-cell spatial omics tools to produce 3D molecularly annotated maps tumors. Its activities overlapped, in some cases catalyzed, revolution biology that saw new technologies being deployed investigate roles tumor heterogeneity micro-environment. See related article Stratton et al., p. 22...
<p>IMAXT Consortium Author List</p>
<div>Summary:<p>The Imaging and Molecular Annotation of Xenografts Tumors Cancer Grand Challenges team was set up with the objective developing “next generation” pathology cancer research by using a combination single-cell spatial omics tools to produce 3D molecularly annotated maps tumors. Its activities overlapped, in some cases catalyzed, revolution biology that saw new technologies being deployed investigate roles tumor heterogeneity micro-environment.</p><p><a...
<p>IMAXT Consortium Author List</p>
<p>Supplementary Figures 1-20</p>
<div>Abstract<p>The intertumor and intratumor heterogeneity of triple-negative breast cancers, which is reflected in diverse drug responses, interplays with tumor evolution. In this study, we developed a preclinical experimental analytical framework using patient-derived xenografts (PDTX) from patients treatment-naïve cancers to test their predictive value personalized cancer treatment approaches. Patients matched PDTXs exhibited concordant responses neoadjuvant therapy two trial...
<p>Short-term olaparib treatment does not cause major genomic changes. <b>A,</b> Growth curves displaying raw data of model 1006 treated with for 11 weeks (purple) or untreated controls (black). Dotted line indicates end treatment, after which, tumors were left to progress until size limits. <b>B,</b> Correlation plots comparing mean VAFs mutations between and (left) post-treated (right) samples. <i>R</i> value calculated using the Spearman...
<p><i>In vivo</i> treatment causes permanent changes to a tumor’s drug response profile. <b>A,</b> Experimental framework of <i>in and <i>ex profiling. <b>B,</b> High-throughput screening data dissociated PDTX cells. AUC plots display the each tumor drugs tested vivo</i>. Color indicates which was previously exposed. <b>C,</b> Dose–response curves models 1040 (top) 1141 (bottom) olaparib BMN-673. Plots compare untreated...
<p>Supplementary Figures 1-20 and Supplementary Tables 1-10 Legends</p>
<p>Olaparib treatment causes permanent phenotypic changes due to TF reprogramming. <b>A,</b> Heatmap displaying <i>z</i>-score (scaled by row) of the top 250 strong and variable genes. Clustering analysis performed using Euclidean distances. Columns indicate PDTX samples (labeled mouse number). <b>B,</b> Top 10 significant gene sets normalized enrichment score (NES) between untreated post-treated samples, identified GSEA (Hallmark sets). DN, down....
<p>A preclinical platform of TNBC PDTXs. <b>A,</b> Clinical treatment and responses the patient cohort from which PDTX models used in this study were derived. <b>B,</b> Experimental framework coclinical trial. <b>C,</b> Top, correlation plots comparing GSEA enrichment scores (Hallmark C6 gene sets) for 1006, 1040, 1022, 1141. Bottom, mutation VAFs model 1006. Correlation was calculated between passages, sister mice, multiple regions same tumor using...