A5071424002- Cancer Cells and Metastasis
- Gene Regulatory Network Analysis
- Ubiquitin and proteasome pathways
- Heat shock proteins research
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Extracellular vesicles in disease
- Monoclonal and Polyclonal Antibodies Research
- Sarcoma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Receptor Mechanisms and Signaling
- Advanced Biosensing Techniques and Applications
- Biosensors and Analytical Detection
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- RNA Research and Splicing
- Molecular Communication and Nanonetworks
- Enzyme Structure and Function
- Histone Deacetylase Inhibitors Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Fluid Dynamics and Turbulent Flows
- Model Reduction and Neural Networks
Oregon Health & Science University
2023-2024
The Ohio State University
2020-2024
The Ohio State University Wexner Medical Center
2023-2024
OHSU Knight Cancer Institute
2023
Cancer Institute (WIA)
2023
University College London
2021
University of California, Davis
2007-2020
Lawrence Berkeley National Laboratory
2015-2020
Intratumoral heterogeneity is associated with aggressive tumor behavior, therapy resistance, and poor patient outcomes. Such thought to be dynamic, shifting over periods of minutes hours in response signaling inputs from the microenvironment. However, models this process have been inferred indirect or post-hoc measurements cell state, leaving temporal details signaling-driven undefined. Here, we developed a live-cell model system which microenvironment-driven dynamics can directly observed...
The formation of functional kinetochores requires the accurate assembly a large number protein complexes. Hsp90–Sgt1 chaperone complex is important for this process; however, its targets are not conserved and exact contribution to kinetochore unclear. Here, we show that human interacts with Mis12 complex, so-called keystone required assemble fraction kinetochore. Inhibition Hsp90 or Sgt1 destabilizes delays proper chromosome alignment due inefficient microtubule-binding sites. Interestingly,...
Abstract The application of quantum dots (QDs) as labels in immunoassay microarrays for the multiplex detection 3‐phenoxybenzoic acid (PBA) and atrazine‐mercapturate (AM) has been demonstrated. PBA AM are biomarkers exposure to pyrethroid insecticides herbicide atrazine, respectively. Microarrays were fabricated by microcontact printing coating antigens line patterns onto glass substrates. Competitive immunoassays successfully performed using QDs (QD560 QD620) reporters. multiplexed...
Verdinexor (KPT-335) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) compound that inhibits the function protein Exportin 1 (XPO1/CRM1). In present study, we sought to characterize expression XPO1 in primary canine osteosarcoma (OS) tumour samples, OS cell lines and normal osteoblasts evaluate vitro activity verdinexor alone or combination with doxorubicin. Canine subset tumours showed increased transcript as compared osteoblast cells. All exhibited dose-dependent...
Abstract Purpose For patients with osteosarcoma, disease-related mortality most often results from lung metastasis—a phenomenon shared many solid tumors. While established metastatic lesions behave aggressively, very few of the tumor cells that reach will survive. By identifying mechanisms facilitate survival disseminated cells, we can develop therapeutic strategies prevent and treat metastasis. Methods We analyzed single cell RNA-sequencing (scRNAseq) data murine metastasis-bearing lungs to...
Histone demethylases are overexpressed or display altered activity in numerous human cancers leading to alterations cell cycle dynamics, DNA repair kinetics, and therapeutic resistance. Consequently, targeting of histone has become an active promising area research oncology. However, the role potential efficacy demethylase inhibition canine remains largely unknown. In present work, we addressed this knowledge gap by exploring inhibitors (HDIs) oral melanoma. Using melanoma lines, determined...
// Alexander E. Davies 1 , Kaitlyn Kortright Kenneth B. Kaplan Department of Cell and Molecular Biology, University California, Davis, CA, USA Correspondence to: Kaplan, e-mail: kbkaplan@ucdavis.edu Keywords: cell stress, adenomatous polyposis coli, microtubules, cancer field effect, Hsp90 Received: February 23, 2015 Accepted: July 10, Published: 22, ABSTRACT Cancer cells up-regulate stress pathways, including the protein chaperone Hsp90. Increases in are believed "buffer" mutant activities...
Nucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Technical obstacles still limit our understanding of the biological functions nucleolar proteins in cell homeostasis and cancer pathogenesis. Since most essential, their abrogation cannot be achieved through conventional approaches. Additionally, activities many connected to physiological concentration. Thus, artificial overexpression might not fully recapitulate endogenous functions....
Abstract Cellular heterogeneity is a prominent feature of the tumor microenvironment, and organization these cells has been linked to clinical outcomes such as disease progression drug resistance. While retrospective analysis patient tumors produced myriad insights, samples are limited highly complex making it challenging validate causality. Here we present an engineered breast microenvironment model, with single cell spatial resolution, systematically identify which phenotypes their...
Abstract In the present study, we investigated relationships between spatiotemporal distribution of growth factors in lung microenvironment, metastatic osteosarcoma cell signaling, and intratumoral gene expression heterogeneity. Osteosarcoma is an aggressive bone malignancy that commonly metastasizes to lungs, resulting significant patient mortality. During metastasis, disseminated cancer cells are exposed microenvironment-derived result signaling pathway activation. Two such pathways...
Abstract Triple negative breast cancer (TNBC) is an aggressive subtype that commonly metastasizes to distant organs, such as the lung, resulting in poor clinical outcomes. TNBC cells overexpress epidermal growth factor receptor (EGFR), a tyrosine kinase (RTK) which when bound by microenvironmental factors, results activation of downstream effector kinases ERK-AKT and initiates transcriptional programs control cell fate. Tumor cells, however, simultaneously receive many inputs from their...
This article introduces an advanced Koopman mode decomposition (KMD) technique—coined Featurized Mode Decomposition (FKMD)—that uses delay embedding and a learned Mahalanobis distance to enhance analysis prediction of high-dimensional dynamical systems. The expands the observation space better capture underlying manifold structures, while adjusts observations based on system’s dynamics. aids in featurizing KMD cases where good features are not priori known. We show that FKMD improves...
Abstract We sought to identify dependencies of slow growing, chemo-resistant osteosarcoma cells that anchor in the metastatic niche. These yield insight into what allows early survive hostile lung environment, as well potential therapeutic targets. In our studies colonization, we identified two distinct populations cells. The first, dubbed “anchor cells”, are prevalent niche where they hypo-proliferative and hyper-secretory. second subpopulation, “growth proliferate rapidly predominate...
Abstract The specific communication of multiple cell types in the tumor microenvironment plays a critical role cancer progression. Current engineering methods have failed to adequately replicate complexities (TME). In particular, generating engineered tissue-like environments with TME has remained challenging. Here we demonstrate capability pattern complex single circuit configurations, using novel microfluidic bioprinting method, study cell-cell early TME. A dispenser (Biopixlar, Fluicell...
Abstract Purpose For patients with osteosarcoma, disease-related mortality most often results from lung metastasis—a phenomenon shared many solid tumors. While established metastatic lesions behave aggressively, very few of the tumor cells that reach will survive. By identifying mechanisms facilitate survival disseminated cells, we can develop therapeutic strategies prevent and treat metastasis. Methods We analyzed single cell RNA-sequencing (scRNAseq) data murine metastasis-bearing lungs to...