Fiona Ginty

Fiona Ginty
GE Global Research · Biosciences

PhD

About

113
Publications
15,456
Reads
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2,755
Citations
Citations since 2017
50 Research Items
1374 Citations
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2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250

Publications

Publications (113)
Article
Full-text available
The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent...
Article
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Background: Mucinous rectal cancer is associated with a higher incidence of microsatellite instability, and a poorer response to neoadjuvant chemoradiotherapy compared to other subtypes of rectal adenocarcinoma. Immune checkpoint inhibitors are an emerging family of anti-cancer therapeutics associated with highly variable outcomes in colorectal ca...
Preprint
Full-text available
There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives...
Article
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Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-describ...
Article
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Lithography based additive manufacturing techniques, specifically digital light processing (DLP), are considered innovative manufacturing techniques for orthopaedic implants because of their potential for construction of complex geometries using polymers, metals, and ceramics. Hydroxyapatite (HA) coupons, printed using DLP, were evaluated for biolo...
Article
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Background Mucinous colorectal cancer (CRC) represents 10% of all CRC and is associated with chemotherapy resistance. This study aimed to determine expression of apoptosis and necroptosis mediators in mucinous CRC. Methods RNA gene expression data were extracted from TCGA. Protein levels in 14 mucinous and 39 non-mucinous tumors were measured by m...
Preprint
Mycobacterium tuberculosis (Mtb) infection induces persistent influx of neutrophils that associates with poor bacterial control and clinical outcome from tuberculosis (TB). Although implicated in TB pathology, the mechanism by which these cells contribute to pathogenesis is poorly understood. Using Cell-DIVE multiplexed immunofluorescence imaging a...
Preprint
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Mapping the human body at single cell resolution in three-dimensions (3D) is an important step toward a "digital twin" model that captures important structure and dynamics of cell-cell interactions. Current 3D imaging methods suffer from low resolution and are limited in their ability to distinguish cell types and their spatial relationships. We pr...
Article
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Cancer immunotherapy can result in lasting tumor regression, but predictive biomarkers of treatment response remain ill-defined. Here, we performed single-cell proteomics, transcriptomics, and genomics on matched untreated and interleukin-2 (IL-2) injected metastases from patients with melanoma. Lesions that completely regressed following intralesi...
Article
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Background The extent of cellular heterogeneity in breast cancer could have potential impact on diagnosis and long-term outcome. However, pathology evaluation is limited to biomarker immunohistochemical staining and morphology of the bulk cancer. Inter-cellular heterogeneity of biomarkers is not usually assessed. As an initial evaluation of the ext...
Article
Full-text available
Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In thi...
Article
The Human Reference Atlas (HRA) aims to map all of the cells of the human body to advance biomedical research and clinical practice. This Perspective presents collaborative work by members of 16 international consortia on two essential and interlinked parts of the HRA: (1) three-dimensional representations of anatomy that are linked to (2) tables t...
Article
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Cancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an...
Article
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Motivation Multiplexed immunofluorescence bioimaging of single-cells and their spatial organization in tissue holds great promise to the development of future precision diagnostics and therapeutics. Current multiplexing pipelines typically involve multiple rounds of immunofluorescence staining across multiple tissue slides. This introduces experime...
Preprint
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Cancer cells' ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells and quantification of 20 cell lineage and apoptosis proteins. Ordinary different...
Preprint
Full-text available
Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Predictive biomarkers for identification of patients with increased risk for disease recurrence are currently lacking, with progress in biomark...
Article
Full-text available
There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). Immunofluorescence multiplexing (MxIF) was used to image and quantify 32 cellular biomarkers in FFPE DCIS tissue microarrays. Over 75,000 DCIS cells from 51 patients (median 9 years follow-up for non-BCE cases) were analysed for profiles pre...
Preprint
This protocol describes the process of validating antibodies (primary/secondary, direct conjugates, and zenon labelled) as per the Cell DIVE™ technology. It also describes the process for determining any antigen effects from the dye inactivation process.
Preprint
The purpose of this protocol is to manually deparaffinize and rehydrate slides for the Cell DIVE™ Platform.
Preprint
This document outlines the workflow for antibody staining, dye inactivation, and imaging as per the Cell DIVE™ technology.
Conference Paper
The extent of intra-tumoral heterogeneity - the variation in the composition of cells in a given tumor and those in the local tumor microenvironment - could have potential impact on diagnosis, treatment planning and subsequent response to treatment. To evaluate the extent of cancer cellular heterogeneity, we conducted quantitative protein marker mu...
Article
Full-text available
Over the last 15 years, advances in immunofluorescence-imaging based cycling methods, antibody conjugation methods, and automated image processing have facilitated the development of a high-resolution, multiplexed tissue immunofluorescence (MxIF) method with single cell-level quantitation termed Cell DIVE TM. Originally developed for fixed oncology...
Preprint
We present a method for automatic cell classification in tissue samples using an automated training set from multiplexed immunofluorescence images. The method utilizes multiple markers stained in situ on a single tissue section on a robust hyperplex immunofluorescence platform (Cell DIVE, GE Healthcare) that provides multi-channel images allowing a...
Article
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An unmet clinical need in solid tumor cancers is the ability to harness the intrinsic spatial information in primary tumors that can be exploited to optimize prognostics, diagnostics and therapeutic strategies for precision medicine. Here, we develop a transformational spatial analytics computational and systems biology platform (SpAn) that predict...
Conference Paper
Colorectal cancer (CRC) has one of the highest Worldwide incidences and mortality rates. Genotoxic chemotherapy following surgery in stage III patients confers treatment benefit to less than 20% of the patients, with more than 50% of stage III patients going on to develop distant metastases. Currently, there are no predictive biomarkers that can id...
Article
Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies. Especially for early stage CRC, prognostic molecular markers are needed to guide therapy. In this study, we first extracted total proteomes from matched pairs of fresh cancer and benign mucosal tissues from 22 CRC patients. Global proteomic profiling with Fourier transfor...
Article
Full-text available
Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated data from protein, genomic and MR imaging from...
Article
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Background: Thymic epithelial tumors are PD-L1-expressing tumors of thymic epithelial origin characterized by varying degrees of lymphocytic infiltration and a predisposition towards development of paraneoplastic autoimmunity. PD-1-targeting antibodies have been evaluated, largely in patients with thymic carcinoma. We sought to evaluate the effica...
Conference Paper
Colorectal cancer (CRC) has one of the highest worldwide incidences and mortality rates. About 25% of stage II patients develop recurrence within 5 years. However, use of adjuvant chemotherapy yields minimal therapeutic benefit. Clinical decision-making in this population would be informed by prognostic and predictive biomarkers that help indicate...
Preprint
Full-text available
Glioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated multiplexed immunofluorescence single cell dat...
Conference Paper
Introduction: Colorectal cancer (CRC) is the third leading cause of cancer related deaths in United States with recurrence after resection-with-a-curative-intent being frequently implicated in these deaths. The basis for CRC recurrence is not completely understood, is multifactorial, and involves dysregulation of heterocellular signaling among tumo...
Conference Paper
Introduction: Colorectal cancer (CRC) is the third leading cause of cancer related deaths in United States with recurrence after resection-with-a-curative-intent being frequently implicated in these deaths. The basis for CRC recurrence is not completely understood, is multifactorial, and involves dysregulation of heterocellular signaling among tumo...
Article
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A systemic analysis of the tumor-immune interactions within the heterogeneous tumor microenvironment is of particular importance for understanding the antitumor immune response. We used multiplexed immunofluorescence to elucidate cellular spatial interactions and T-cell infiltrations in metastatic melanoma tumor microenvironment. We developed two n...
Preprint
Full-text available
An unmet clinical need in solid tumor cancers is the ability to harness the intrinsic spatial information in primary tumors that can be exploited to optimize prognostics, diagnostics and therapeutic strategies for precision medicine. We have developed a transformational spatial analytics (SpAn) computational and systems biology platform that predic...
Article
Background: Ductal carcinoma in situ (DCIS) accounts for at least 20% of breast cancers. Factors associated with recurrence of DCIS or progression to invasive carcinoma are not well delineated. The goals of the current study were to profile the epithelial cells using the GE Cell DIVE™ immuno-fluorescent based analyses. This was coupled with semi-au...
Article
Full-text available
Plasma cell myeloma (PCM), with a highly heterogeneous clinical behavior and response to therapy, accounts for approximately 10% of hematologic malignancies. Current diagnostic and prognostic tests include serum-based assays, multiparametric flow cytometric analysis of bone marrow aspirates, morphologic and immunohistochemical analysis of bone marr...
Article
We developed and deployed a workflow for generating multi-scale, multiparametric imaging data, feature extraction and/or converting to higher scales which equips multiple analysis approaches to differentiate clinically variable phenotypes of glial tumors. The workflow quantifies spatial heterogeneity (concordance of adjoining cells) and molecular h...
Article
Full-text available
Heterogeneous patterns of mutations and RNA expression have been well documented in invasive cancers. However, technological challenges have limited the ability to study heterogeneity of protein expression. This is particularly true for pre-invasive lesions such as ductal carcinoma in situ of the breast. Cell-level heterogeneity in ductal carcinoma...
Article
p>We introduce THRIVE (Tumor Heterogeneity Research Interactive Visualization Environment), an open-source tool developed to assist cancer researchers in interactive hypothesis testing. The focus of this tool is to quantify spatial intratumoral heterogeneity (ITH), and the interactions between different cell phenotypes and noncellular constituents....
Article
Background: Understanding the spatial interactions between tumor and immune cells in the heterogeneous tumor microenvironment is pivotal to improve clinical outcomes of immunotherapy. Various multiplexed imaging platforms have been recently developed to visualize the different immune cell subtypes with various distribution patterns that can impact...
Article
The hallmarks of cancer consist of ten categories that serve as an organizing principle and framework for understanding neoplastic disease. The ten hallmarks include activating invasion and metastasis, avoiding immune destruction, deregulating cellular energetics, enabling replicative immortality, evading growth suppressors, genome instability and...
Article
Extracting biologically relevant data from radiology images can enable better monitoring of disease progression and therapy response. The field of radiogenomics is providing new approaches for such genomic/radiology correlations. However, there are several challenges in validation and clinical translation in that few DNA mutations are shared betwee...
Article
Radiogenomics or radiomics is an emerging field where tumor genomic data is correlated with radiology image features, thereby potentially providing more biological information about the tumor phenotype. A central challenge is the potential for model over-fitting due to analysis of many thousands of genomic data-points with hundreds of corresponding...
Article
Background: Ductal carcinoma in situ (DCIS) accounts for at least 20% of breast cancers. Factors associated with recurrence of DCIS or progression to invasive carcinoma are not well delineated. The goals of the current study were to profile the epithelial and immune cells using the MultiOmyx hyperplexed immuno-fluorescent based analyses. This was c...
Article
s: AACR Special Conference on Tumor Immunology and Immunotherapy; October 20-23, 2016; Boston, MA The variable clinical success with immune checkpoint inhibitors in the treatment of solid tumors challenges us to further understand the regulatory mechanisms of immune cells infiltration – a critical step of tumor elimination – in a highly heterogeno...
Article
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Background Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME) are key contributors to heterogeneity. Methods We demonstrate how to quantif...
Article
Immune response to tumor growth and development is highly complex and varies with stromal and tumor cell composition and secreted factors. Different immune cell types can have opposing functions (tumor suppressive or immune suppressive) and their density, location and activation state can have profound effects on tumor outcome. Routine immune-profi...
Article
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The phenotypic diversity of cancer results from genetic and nongenetic factors. Most studies of cancer heterogeneity have focused on DNA alterations, as technologies for proteomic measurements in clinical specimen are currently less advanced. Here, we used a multiplexed immunofluorescence staining platform to measure the expression of 27 proteins a...
Article
Full-text available
Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, w...
Article
Full-text available
ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent. Major limitations of some outcome studies include small sample size and heterogeneous patient popula...
Article
Although anti-angiogenic therapy has emerged as a leading modality in treating human cancer, further improvements in the duration and frequency of clinical response of various human cancers remain important clinical needs. Maturity of the tumor vasculature has been identified as one of the major determinants of response of cancers to anti-angiogeni...
Article
Breast cancer is the most common malignancy in Singapore women with rising incidence across all ethnic groups (Chinese, Malays and Indians). Ductal carcinoma in situ (DCIS) is the earliest non-invasive stage of disease and has been shown to account for approximately 26% of diagnoses in all women participating in the Breast-Screen Singapore program....
Patent
Improved systems and methods for the analysis of digital images are provided. More particularly, the present disclosure provides for improved systems and methods for the analysis of digital images of biological tissue samples. Exemplary embodiments provide for: i) segmenting, ii) grouping, and iii) quantifying molecular protein profiles of individu...
Patent
Improved systems and methods for the analysis of digital images are provided. More particularly, the present disclosure provides for improved systems and methods for the analysis of digital images of biological tissue samples. Exemplary embodiments provide for: i) segmenting, ii) grouping, and iii) quantifying molecular protein profiles of individu...
Article
Full-text available
Cancer is a multifaceted disease characterized by heterogeneous genetic alterations and cellular metabolism, at the organ, tissue, and cellular level. Key features of cancer heterogeneity are summarized by 10 acquired capabilities, which govern malignant transformation and progression of invasive tumors. The relative contribution of these hallmark...
Article
Background: While routinely collected human tumor specimen can now readily be examined for genetic alterations on a genome wide scale, multi-parameter measurements of protein expression remain challenging. We developed a multiplexed fluorescence microscopy method (MultiOmyxTM) for the quantitative characterization of multiple analytes in formalin-f...
Patent
Full-text available
The invention relates generally to a process of analyzing and visualizing the expression of biomarkers in an individual cell wherein the cell is examined to develop patterns of expression by using a grouping algorithm, and a system to perform and display the analysis.
Article
Over the last three decades, the incidence of early-stage breast cancer has doubled while the incidence of late stage breast cancer has slightly decreased; however, the standard treatment for both has not changed significantly in the last 10 years. Of those diagnosed with early-stage breast cancer, 30% will develop recurrent disease, though there i...
Article
Full-text available
Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2)) und...
Article
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Limitations on the number of unique protein and DNA molecules that can be characterized microscopically in a single tissue specimen impede advances in understanding the biological basis of health and disease. Here we present a multiplexed fluorescence microscopy method (MxIF) for quantitative, single-cell, and subcellular characterization of multip...
Article
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Quantitative fluorescence microscopy is severely hindered by intrinsic autofluorescence (AF). Endogenous fluorescent molecules in tissue and cell samples emit fluorescence that often dominates signals from specific dyes. This makes AF removal critical to the development and practice of quantitative fluorescence microscopy. In this study, we showed...
Article
2097 Background: GBM is the most common brain tumor in humans and has a dismal prognosis. Although antiangiogenic therapy (bevacizumab) is an option for GBM, there is still unmet need to understand tumor pathophysiology and predictive biomarkers. We built a tissue based multiplexed immunofluorescent assays and developed algorithms to identify and q...
Article
Full-text available
Epithelial organ morphogenesis involves reciprocal interactions between epithelial and mesenchymal cell types to balance progenitor cell retention and expansion with cell differentiation for evolution of tissue architecture. Underlying submandibular salivary gland branching morphogenesis is the regulated proliferation and differentiation of perhaps...
Article
Introduction: Breast cancer is the most common cancer for women worldwide. HER2 expression and gene copy number are important when determining eligibility for adjuvant therapy and/or chemotherapy medications. One challenging issue for breast cancer testing is intratumoral heterogeneity of HER2 gene amplification. Intratumoral heterogeneity can make...