A5072788736- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Breast Cancer Treatment Studies
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Nuts composition and effects
- Sirtuins and Resveratrol in Medicine
- Lymphoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Advanced Breast Cancer Therapies
- Chronic Lymphocytic Leukemia Research
- Genomics, phytochemicals, and oxidative stress
- HER2/EGFR in Cancer Research
- Ovarian cancer diagnosis and treatment
- Immune cells in cancer
- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- Melanoma and MAPK Pathways
- Angiogenesis and VEGF in Cancer
City Of Hope National Medical Center
2020-2025
Beckman Research Institute
2019-2023
City of Hope
2017-2023
University of Utah
2011-2021
Weatherford College
2021
Kyushu University
2021
Cancer Institute (WIA)
2021
Advanced Imaging Research (United States)
2017
Huntsman Cancer Institute
2012-2017
University of Arizona
2017
The Cancer Genome Atlas (TCGA) RNA-Sequencing data are used widely for research. TCGA provides 'Level 3' data, which have been processed using a pipeline specific to that resource. However, we found experimentally derived this produces gene-expression values vary considerably across biological replicates. In addition, some analysis tools require integer-based read counts, not provided with the Level 3 data. As an alternative, reprocessed 9264 tumor and 741 normal samples 24 cancer types...
Abstract ABCB1 encodes Multidrug Resistance protein (MDR1), an ATP-binding cassette member involved in the cellular efflux of chemotherapeutic drugs. Here we report that ovarian and breast samples from chemotherapy treated patients are positive for multiple transcriptional fusions involving , placing it under control a strong promoter while leaving its open reading frame intact. We identified 15 different fusion partners as well with distinct events. The partner gene selected depended on...
The purpose of this study was to develop an integrated genomic-based approach personalized treatment patients with advanced-stage ovarian cancer. We have used gene expression profiles identify likely be resistant primary platinum-based chemotherapy and also alternate targeted therapeutic options for de novo platinum-resistant disease.A model that predicts response therapy developed using a training set 83 serous cancers tested on 36-sample external validation set. In parallel, signatures...
Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic phenotypic subclonal evolution of four cancers through years treatment better understand how become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk single-cell RNA sequencing reveal acquisition malignant...
Rationale: Molecular phenotyping of chronic obstructive pulmonary disease (COPD) has been impeded in part by the difficulty obtaining lung tissue samples from individuals with impaired function.Objectives: We sought to determine whether COPD-associated processes are reflected gene expression profiles bronchial airway epithelial cells obtained bronchoscopy.Methods: Gene profiling brushings 238 current and former smokers without COPD was performed using Affymetrix Human 1.0 ST...
Ovarian cancer is typified by the development of chemotherapy resistance. Chemotherapy resistance associated with high aldehyde dehydrogenase (ALDH) enzymatic activity, increased "stemness," and expression stem cell marker CD133. As such, ALDH activity has been proposed as a therapeutic target. Although it remains controversial which 19 family members drive resistance, ALDH1A have primarily linked resistant stemness. We identified two selective inhibitors (ALDH1Ai). ALDH1Ai preferentially kills CD133
Significance The evolution of peripheral immune cell abundance and signaling over time, as well how these cells interact with the tumor, may impact a cancer patient’s response to therapy. By developing an ecological population model, we provide evidence dynamic predator–prey-like relationship between circulating tumor size in patients that respond immunotherapy. This is not found either are nonresponsive immunotherapy or during chemotherapy. Single-cell RNA sequencing serial blood samples...
Abstract Purpose: Breast cancer is a heterogeneous disease, and markers for disease subtypes therapy response remain poorly defined. For that reason, we employed prospective neoadjuvant study in locally advanced breast to identify molecular signatures of gene expression correlating with known prognostic clinical phenotypes, such as inflammatory or the presence hypoxia. In addition, defined correlate chemotherapy. Experimental Design: Tissue was collected under ultrasound guidance from...
Over the past two decades, many biotechnology platforms have been developed for high-throughput gene expression profiling. However, because each platform is subject to technology-specific biases and produces distinct raw-data distributions, researchers experienced difficulty in integrating data across platforms. Data integration crucial data-generating consortiums, transitioning newer profiling technologies, individuals seeking aggregate experiments. We address this need with our Universal...
Abstract Introduction Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies. Phosphatidylinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways are frequently activated in TNBC patient tumors at the genome, gene expression protein levels, mTOR inhibitors have been shown to inhibit growth cell lines. We describe a panel patient-derived xenografts representing multiple subtypes use them test preclinical drug efficacy two inhibitors, sirolimus...
The interplay of positive and negative interactions between drug-sensitive resistant cells influences the effectiveness treatment in heterogeneous cancer cell populations. Here, we study estrogen receptor-positive breast lineages that are sensitive to ribociclib-induced cyclin-dependent kinase 4 6 (CDK4/6) inhibition. In mono- coculture, find grow compete more effectively absence treatment. During with ribociclib, survive proliferate better when grown together than monoculture, termed...
The Emu-myc transgenic mouse has provided a valuable model for the study of B-cell lymphoma. Making use gene expression analysis and, in particular, signatures cell signaling pathway activation, we now show that several forms B lymphoma can be identified mice associated with time tumor onset. Furthermore, one form pre-B character is shown to resemble human Burkitt lymphoma, whereas others exhibit more differentiated characteristics and similarity diffuse large pattern expression, as well...
Perhaps the major challenge in developing more effective therapeutic strategies for treatment of breast cancer patients is confronting heterogeneity disease, recognizing that not one disease but multiple disorders with distinct underlying mechanisms. Gene-expression profiling studies have been used to dissect this complexity, and our previous identified a series intrinsic subtypes define populations respect survival. Additional work has also signatures oncogenic pathway deregulation as well...
Intraperitoneal dissemination of ovarian cancers is preceded by the development chemoresistant tumors with malignant ascites. Despite high levels chemoresistance and relapse observed in cancers, there are no vitro models to understand situ. Method: We describe a highly integrated approach establish an model stemness cancer, using 3D hanging drop spheroid platform. The was established serially passaging non-adherent spheroids. At each passage, effectiveness evaluated via measures...
Abstract Immune evasion by cancer cells involves reshaping the tumor microenvironment (TME) via communication with non-malignant cells. However, resistance-promoting interactions during treatment remain lesser known. Here we examine composition, communication, and phenotypes of tumor-associated in serial biopsies from stage II III high-risk estrogen receptor positive (ER+ ) breast cancers patients receiving endocrine therapy (letrozole) as single agent or combination ribociclib, a...
Abstract The evolution of resistance in high-grade serous ovarian cancer (HGSOC) cells following chemotherapy is only partially understood. To understand the selection factors driving heterogeneity before and through adaptation to treatment, we profile single-cell RNA-sequencing (scRNA-seq) transcriptomes HGSOC tumors collected longitudinally during therapy. We analyze scRNA-seq data from two independent patient cohorts reveal that driven by three archetypal phenotypes, defined as oncogenic...