Joe W Gray

Joe W Gray
Oregon Health and Science University | OHSU · Department of Biomedical Engineering

PhD

About

1,006
Publications
99,886
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
88,714
Citations
Introduction
Skills and Expertise
Additional affiliations
January 2011 - June 2015
Oregon Health and Science University
Position
  • Chair, Biomedical Engineering, Director of OHSU Center for Spatial Systems Biomedicine
Education
September 1968 - August 1972
Kansas State University
Field of study
  • Physics
September 1964 - August 1968
Colorado School of Mines
Field of study
  • Engineering Physics

Publications

Publications (1,006)
Article
Full-text available
Immune checkpoint inhibitors (ICIs) targeting PD-L1 and PD-1 have improved survival in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients respond to ICIs, highlighting the need for superior immunotherapy. Herein, we report on a nanoparticle-based immunotherapy termed ARAC (Antigen Relea...
Article
Full-text available
Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we integrated high-throughput and high-content techniques—an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses and multiplexed imaging of tumor microenviron...
Article
Background: Emerging data supports PARPi combinations, including PARPi with immune checkpoint blockade (ICB), as effective therapies in TNBC. The Adaptive Multi-Drug Treatment of Evolving Cancers (AMTEC) trial (NCT03801369) is evaluating the PARPi + ICB combination of olaparib (ola) + durvalumab (durva) in mTNBC patients (pts). Deep profiling of pa...
Article
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer in which the tumor microenvironment (TME) is prognostic, with increased tumor-infiltrating lymphocytes predicting a good prognosis. Positive clinical trials of immune checkpoint inhibitors in TNBC further highlight the TME’s importance, but its single-cell composition an...
Article
Full-text available
Multiplex imaging technologies are increasingly used for single-cell phenotyping and spatial characterization of tissues; however, transparent methods are needed for comparing the performance of platforms, protocols and analytical pipelines. We developed a python software, mplexable, for reproducible image processing and utilize Jupyter notebooks t...
Article
Full-text available
Image-based cell phenotyping relies on quantitative measurements as encoded representations of cells; however, defining suitable representations that capture complex imaging features is challenged by the lack of robust methods to segment cells, identify subcellular compartments, and extract relevant features. Variational autoencoder (VAE) approache...
Patent
Techniques and systems for translating images of biological samples stained according to a first staining technique into images representing the biological samples stained accord ing to a second staining technique. In various implementations , the first staining technique can include a histopathological staining technique and the second staining te...
Article
Full-text available
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells and extrinsic microenvironmental influences change during treatment. To support the development of methods for identifying these mechanisms in individual people, here we present an omic and multidimensional spatial (OMS) atlas generated from four seri...
Article
The first-line treatment of advanced and metastatic human epidermal growth factor receptor type 2 (HER2+) breast cancer requires two HER2-targeting antibodies (trastuzumab and pertuzumab) and a taxane (docetaxel or paclitaxel). The three-drug regimen costs over $320,000 per treatment course, requires a 4 h infusion time, and has many adverse side e...
Article
Full-text available
A number of highly multiplexed immunostaining and imaging methods have advanced spatial proteomics of cancer for improved treatment strategies. While a variety of methods have been developed, the most widely used methods are limited by harmful signal removal techniques, difficulties with reagent production and antigen sensitivity. Multiplexed immun...
Article
Full-text available
Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges in accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess heterogeneity that exists among multiple metastatic lesions throughout the treatment course. We developed a precision oncology platform that co...
Article
Full-text available
In a pilot study, we evaluated the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities as they emerge under therapeutic stress engendered by poly-ADP-ribose polymerase (PARP) inhibitors (PARPi). In a BRCA-mutant basal breast cance...
Preprint
Full-text available
Multiplex imaging technologies are increasingly used for single-cell phenotyping and spatial characterization of tissues; however, transparent methods are needed for comparing the performance of platforms, protocols and analytical pipelines. We developed a python software, jinxif, for reproducible image processing and utilize Jupyter notebooks to s...
Preprint
Full-text available
Ensemble of predictions is known to perform better than individual predictions taken separately. However, for tasks that require heavy computational resources, \textit{e.g.} semantic segmentation, creating an ensemble of learners that needs to be trained separately is hardly tractable. In this work, we propose to leverage the performance boost offe...
Preprint
Full-text available
Systematically identifying synergistic combinations between targeted agents and immunotherapies in cancer based on genomic or other static biomarkers remains elusive. Here we integrate two novel high-content and high-throughput techniques, an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses; and spati...
Preprint
Better methods are needed to identify effective combinations of immunotherapies with chemotherapies and targeted anti-cancer agents. Here we present a Multiplex Implantable Microdevice Assay (MIMA) system for rapid in vivo assessment of the effects of multiple, spatially separate anticancer drugs directly in the complex tumor microenvironment. In p...
Preprint
Full-text available
The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understand...
Article
Full-text available
The success of immunotherapy with immune checkpoint inhibitors (ICIs) in a subset of individuals has been very exciting. However, in many cancers, responses to current ICIs are modest and are seen only in a small subsets of patients. Herein, a widely applicable approach that increases the benefit of ICIs is reported. Intratumoral administration of...
Article
Full-text available
In article number 2100628, Wassana Yantasee and co‐workers investigate how Augmenting Immune Response and Inhibiting Suppressive Environment of tumors‐02 (AIRISE‐02) activates an antitumor immune response. AIRISE‐02 is a nanoparticle co‐delivering STAT3 siRNA and CpG intratumorally, utilizing local tumor antigens to train the immune system to kill...
Article
Full-text available
Background HER2-amplified breast cancer is a clinically defined subtype of breast cancer for which there are multiple viable targeted therapies. Resistance to these targeted therapies is a common problem, but the mechanisms by which resistance occurs remain incompletely defined. One mechanism that has been proposed is through mutation of genes in t...
Article
Full-text available
Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor...
Article
Full-text available
The emergence of megascale single-cell multiplex tissue imaging (MTI) datasets necessitates reproducible, scalable, and robust tools for cell phenotyping and spatial analysis. We developed open-source, graphics processing unit (GPU)-accelerated tools for intensity normalization, phenotyping, and microenvironment characterization. We deploy the tool...
Preprint
Full-text available
Recent advances in Focused Ion Beam-Scanning Electron Microscopy (FIB- SEM) allows the imaging and analysis of cellular ultrastructure at nanoscale resolution, but the collection of labels and/or noise-free data sets has several challenges, often immutable. Reasons range from time consuming manual annotations, requiring highly trained specialists,...
Preprint
Full-text available
A deeper understanding of the cellular and subcellular organization of tumor cells and their interactions with the tumor microenvironment will shed light on how cancer evolves and guide effective therapy choices. Electron microscopy (EM) images can provide detailed view of the cellular ultrastructure and are being generated at an ever-increasing ra...
Article
Full-text available
Despite the availability of multiple HER2-targeted treatments, therapeutic resistance in HER2+ breast cancer remains a clinical challenge. Intratumor heterogeneity for HER2 and resistance-conferring mutations (e.g., PIK3CA) have been investigated in response and resistance to HER2-targeting agents, while the role of divergent cellular phenotypes an...
Preprint
Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor...
Article
The use of ex vivo drug sensitivity testing to predict drug activity in individual patients has been actively explored for almost 50 years without delivering a generally useful predictive capability. However, extended failure should not be an indicator of futility. This is especially true in cancer research, where ultimate success is often preceded...
Preprint
Full-text available
Immune checkpoint inhibitors (ICIs) targeting PD-L1 and PD-1 have improved survival in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients respond to ICIs, highlighting the need for superior immunotherapy. Herein, we developed a nanoparticle-based immunotherapy termed ARAC (Antigen Relea...
Preprint
Immune checkpoint inhibitors (ICIs) targeting PD-L1 and PD-1 have improved survival in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients respond to ICIs, highlighting the need for superior immunotherapy. Herein, we developed a nanoparticle-based immunotherapy termed ARAC (Antigen Relea...
Article
The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and r...
Preprint
Full-text available
The emergence of megascale single-cell multiplex tissue imaging (MTI) datasets necessitates reproducible, scalable, and robust tools for cell phenotyping and spatial analysis. We developed open-source, graphics processing unit (GPU)-accelerated tools for intensity nor-malization, phenotyping, and microenvironment characterization. We deploy the too...
Preprint
Full-text available
Metastatic cancers often respond to treatment initially but almost universally escape therapeutic control through molecular mechanisms intrinsic to tumor cells, as well as extrinsic influences from immune cells, stroma, and structural microenvironments. We explore the extent to which we can learn these mechanisms and associated therapeutic vulnerab...
Article
Full-text available
Several years ago, the SUM panel of human breast cancer cell lines was developed, and these cell lines have been distributed to hundreds of labs worldwide. Our lab and others have developed extensive omics data sets from these cells. More recently, we performed genome-scale shRNA essentiality screens on the entire SUM line panel, as well as on MCF1...
Article
Full-text available
Mechanistic disease progression studies using animal models require objective and quantifiable assessment of tissue pathology. Currently quantification relies heavily on staining methods which can be expensive, labor/time-intensive, inconsistent across laboratories and batch, and produce uneven staining that is prone to misinterpretation and invest...
Conference Paper
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) patients, who often present with stage III or IV disease, face a dismal prognosis as the 5-year survival rate remains below 10%. Recent studies have revealed that CD4 + T, CD8 + T, and/or B cells in specific spatial arrangements relative to intratumoral regions correlate with clinical outcome for patients, bu...
Article
Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed expression profiles of ∼210 cl...
Article
Full-text available
Abstract Spatially-resolved molecular profiling by immunostaining tissue sections is a key feature in cancer diagnosis, subtyping, and treatment, where it complements routine histopathological evaluation by clarifying tumor phenotypes. In this work, we present a deep learning-based method called speedy histological-to-immunofluorescent translation...
Conference Paper
p>Triple negative breast cancer (TNBC) lacks expression of hormone receptors (ER and PR) and HER2 and is characterized by aggressive disease with poor outcomes. Recent work suggests that TNBC also has a high degree of intratumoral heterogeneity, as measured by lineage differentiation status. This heterogeneity may impact therapeutic response, as it...
Article
Full-text available
Background Glioblastoma is a rapidly fatal brain cancer that exhibits extensive intra- and inter-tumoral heterogeneity. Improving survival will require the development of personalized treatment strategies that can stratify tumors into subtypes that differ in therapeutic vulnerability and outcomes. Glioblastoma stratification has been hampered by in...
Article
Comparison of 3D Protocols in Metastatic Breast Cancer Tumors - Erin Stempinski, Jessica Riesterer, Christopher K E Bleck, Claudia Lopez, Joe Gray
Article
Imaging Bioprinted Model Systems for Metastatic Breast Cancer Studies - Jessica Riesterer, Arun Singh, Erin Stempinski, Steven Adamou, Cecilia Bueno, Hannah Smith, Claudia Lopez, Joe Gray
Article
Full-text available
Significance: Advanced genetic characterization has informed cancer heterogeneity and the challenge it poses to effective therapy; however, current methods lack spatial context, which is vital to successful cancer therapy. Conventional immunolabeling, commonplace in the clinic, can provide spatial context to protein expression. However, these tech...
Article
e13092 Background: Longitudinal analysis of serial tumor biopsies is an under-utilized approach to studying adaptive mechanisms of resistance. We have established a comprehensive analytic platform to evaluate real-time trial sample analysis to inform precision oncology combinations in mTNBC. The primary endpoint of the study is feasibility of compl...
Conference Paper
Full-text available
Most deep learning segmentation architectures require a large amount of training data, comprised of thousands of manually annotated images. Despite being time consuming to create, manual annotations are more accurate than algorithmic segmentations and, therefore, result in better training. Here we describe a strategy that utilizes iterative learnin...
Preprint
Full-text available
Mechanistic studies of pancreatic disease progression using animal models require objective and quantifiable assessment of tissue changes among animal cohorts. Disease state quantification, however, relies heavily on tissue immunostaining, which can be expensive, labor-and time-intensive, and all too often produces uneven staining that is prone to...
Article
This Perspective explores the application of machine learning toward improved diagnosis and treatment. We outline a vision for how machine learning can transform three broad areas of biomedicine: clinical diagnostics, precision treatments, and health monitoring, where the goal is to maintain health through a range of diseases and the normal aging p...
Article
Crucial transitions in cancer—including tumor initiation, local expansion, metastasis, and therapeutic resistance—involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecede...
Chapter
Recent developments in large format electron microscopy have enabled generation of images that provide detailed ultrastructural information on normal and diseased cells and tissues. Analyses of these images increase our understanding of cellular organization and interactions and disease-related changes therein. In this manuscript, we describe a wor...
Article
Full-text available
Recent advances in multiplexed imaging technologies promise to improve the understanding of the functional states of individual cells and the interactions between the cells in tissues. This often requires compilation of results from multiple samples. However, quantitative integration of information between samples is complicated by variations in st...
Conference Paper
Full-text available
Successful cancer treatment continues to elude modern medicine and its arsenal of therapeutic strategies. Therapy resistance is driven by significant tumor heterogeneity, complex interactions between malignant, microenvironmental and immune cells and cross talk between signaling pathways. Advances in molecular characterization technologies such as...
Article
Predicting primary site of secondary liver cancer with a neural estimator of metastatic origin," Abstract Purpose: Pathologists rely on relevant clinical information, visual inspection of stained tissue slide morphology, and sophisticated molecular diagnostics to accurately infer the biological origin of secondary metastatic cancer. While highly ef...
Article
Full-text available
Successful cancer treatment continues to elude modern medicine and its arsenal of therapeutic strategies. Therapy resistance is driven by significant tumor heterogeneity, complex interactions between malignant, microenvironmental and immune cells and cross talk between signaling pathways. Advances in molecular characterization technologies such as...
Chapter
Full-text available
Immunotherapy harnesses the power of the adaptive immune system and has revolutionized the field of oncotherapy, as novel therapeutic strategies have been introduced into clinical use. The development of immune checkpoint inhibitors has led to durable control of disease in a subset of advanced cancer patients, such as those with melanoma and non-sm...