Tao Liu

Tao Liu
Pacific Northwest National Laboratory | PNNL · Biological Sciences Division

Ph.D.

About

280
Publications
70,667
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13,226
Citations
Additional affiliations
September 2003 - present
Pacific Northwest National Laboratory
Position
  • Sr. Scientist

Publications

Publications (280)
Article
Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time‐consuming and typically have poor reproducibility. Here we describe a simp...
Article
Full-text available
Small extracellular vesicles (sEVs) are cell-released vesicles ranging from 30-150nm in size. They have garnered increasing attention because of their potential for both the diagnosis and treatment of disease. The diversity of sEVs derives from their biological composition and cargo content. Currently, the isolation of sEV subpopulations is primari...
Article
Full-text available
Background Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscap...
Article
Full-text available
Introduction: Breast cancer (BC) is classified into four widely-accepted intrinsic subtypes based on PAM (Prediction Analysis of Microarray) 50 gene expression profiles: Luminal A (LumA), Luminal B (LumB), Her2-enriched (Her2) and basal-like (Basal). Recent multi-omic studies of human BC have identified many potential therapeutic biomarkers for the...
Article
Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal pro...
Article
Acute myeloid leukemia (AML) is a deadly form of blood cancer primarily characterized by genetic abnormalities that guide treatment strategies. In recent years, several new therapies have emerged to target these genetic abnormalities such as gilteritinib or quizartinib, which target an internal tandem duplication (ITD) of the FLT3 gene. Additional...
Article
Acute myeloid leukemia (AML) is a blood malignancy of poor prognosis with marked heterogeneity. To elucidate the underlying mechanisms that drive AML as part of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) effort, we performed comprehensive genomics, transcriptomics, proteomics including multiple post-translational modifications (phosph...
Article
To unravel the molecular mechanisms underlying high-grade glioma (HGG) in adolescent and young adult (AYA) patients, we conducted a comprehensive proteogenomic analysis for 34 AYA (age 15-40) and 59 pediatric (age 0-15) HGG cases. Our approach involved whole genome sequencing, methylation profiling, RNA sequencing, and a suite of mass spectrometry-...
Article
Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The pro-inflammatory cytokine IL-1 is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that...
Article
Screening for ovarian cancer has been hindered by the lack of a clinical assay with sufficient sensitivity and specificity for use in the general population. Since bodily fluids in close proximity to tumors may contain higher concentrations of tumor biomarkers than blood samples, we hypothesized that proteins shed by ovarian cancer tumors could be...
Article
Acute myeloid leukemia (AML) is a blood malignancy of poor prognosis with marked heterogeneity. To elucidate the underlying mechanisms that drive AML as part of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) effort, we performed large scale comprehensive genomics, transcriptomics, proteomics including multiple post-translational modificat...
Article
Acute myeloid leukemia is a poor-prognosis cancer commonly stratified by genetic aberrations, but these mutations are often heterogeneous and fail to consistently predict therapeutic response. Here, we combine transcriptomic, proteomic, and phosphoproteomic datasets with ex vivo drug sensitivity data to help understand the underlying pathophysiolog...
Preprint
Full-text available
Microglia, the innate immune cells of the central nervous system, have been genetically implicated in multiple neurodegenerative diseases. We previously mapped the genetic regulation of gene expression and mRNA splicing in human microglia, identifying several loci where common genetic variants in microglia-specific regulatory elements explain disea...
Article
The National Cancer Institute Clinical Proteomic Atlas Consortium (CPTAC) herein reports our deep characterization of 228 grade IV IDH1 WT and mutant astrocytomas (including 28 matched primary and recurrent GBMs) using 15 proteogenomic and metabolomic platforms. Major advances over our first CPTAC GBM report (Wang et al., 2021, Cancer Cell), are th...
Article
Proteogenomics refers to the integration of comprehensive genomic, transcriptomic, and proteomic measurements from the same samples with the goal of fully understanding the regulatory processes converting genotypes to phenotypes, often with an emphasis on gaining a deeper understanding of disease processes. Although specific genetic mutations have...
Article
Full-text available
Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. Material and methods To investigate this, we used unbia...
Article
Full-text available
Background Lysine carbamylation is a biomarker of rheumatoid arthritis and kidney diseases. However, its cellular function is understudied due to the lack of tools for systematic analysis of this post-translational modification (PTM). Methods We adapted a method to analyze carbamylated peptides by co-affinity purification with acetylated peptides...
Article
Full-text available
Simple Summary Lung cancer remains one of the deadliest cancers, with the worst survival rate. Cells from the airway lining of patients at high risk for lung cancer differentially express proteins that may serve as biomarkers for early detection of lung cancer. Previously, we identified candidate proteins in patients at high risk for lung cancer. I...
Preprint
With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures important tissue heterogeneity, which make it impossible for proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single...
Article
We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activ...
Article
Acute myeloid leukemia (AML) is a deadly blood cancer that remains largely classified by genetic aberrations, which inform therapy stratification. However, therapeutic response cannot be predicted or explained by genetic abnormalities alone. The integration of multiple omics, consisting of genomic, transcriptomic, proteomic, and phosphoproteomic me...
Article
Full-text available
Endometrial carcinoma (EC) is the most common gynecologic cancer diagnosed in developed countries, with incidence on the rise globally. Over the past decade, EC outcomes have worsened in the United States, despite the fact that early stage, well-differentiated cancers are often cured by simple hysterectomy. Work by the Cancer Genome Atlas Consortiu...
Article
Full-text available
Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis o...
Article
Full-text available
Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target disco...
Chapter
Full-text available
Early detection of solid tumors through a simple screening process, such as the proteomic analysis of biofluids, has the potential to significantly alter the management and outcomes of cancers. The application of advanced targeted proteomics measurements and data analysis strategies to uniformly collected serum or plasma samples would enable longit...
Article
Full-text available
Effective phosphoproteome of nanoscale sample analysis remains a daunting task, primarily due to significant sample loss associated with non-specific surface adsorption during enrichment of low stoichiometric phosphopeptide. We develop a tandem tip phosphoproteomics sample preparation method that is capable of sample cleanup and enrichment without...
Article
Full-text available
Prostate cancer (PCa) is the second leading cause of male cancer-related deaths in the United States. The pre-mature forms of prostate-specific antigen (PSA), proPSA, were shown to be associated with PCa. However, there is a technical challenge in the development of antibody-based immunoassays for specific recognition of each individual proPSA isof...
Article
Introduction and study purpose: Prostate cancer (PCa) is the leading type of newly diagnosed cancer and second leading cause of cancer death in American men. Significant racial differences in PCa incidence and mortality have been long-reported in the U.S., with Black men demonstrating a disproportionately higher burden of disease compared to White...
Article
Full-text available
Tumor-initiating cells with reprogramming plasticity or stem-progenitor cell properties (stemness) are thought to be essential for cancer development and metastatic regeneration in many cancers; however, elucidation of the underlying molecular network and pathways remains demanding. Combining machine learning and experimental investigation, here we...
Preprint
Full-text available
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometr...
Article
Full-text available
Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective abla...
Article
Full-text available
Despite advances in proteomic technologies, clinical translation of plasma biomarkers remains low, partly due to a major bottleneck between the discovery of candidate biomarkers and costly clinical validation studies. Due to a dearth of multiplexable assays, generally only a few candidate biomarkers are tested, and the validation success rate is ac...
Article
mRNA processing related pathways, including spliceosome and ribosome are over-expressed and unregulated in cancer cells. To investigate the mRNA processing pathways in patient samples, we performed a comprehensive, tandem mass tag (TMT) labeling-based proteome and phosphoproteome profiling of the normal and ovarian cancerous tissues from patients t...
Article
Full-text available
The Extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase I (2013-2018), Phase 2 of the program (ERCC2, 2019-2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducibl...
Preprint
Full-text available
Effective phosphoproteome of nanoscale sample analysis remains a daunting task, primarily due to significant sample loss associated with non-specific surface adsorption during enrichment of low stoichiometric phosphopeptide. We developed a novel tandem tip phosphoproteomics sample preparation method that is capable of sample cleanup and enrichment...
Article
Full-text available
Cellular components are non-randomly arranged with respect to the shape and polarity of the whole cell.1, 2, 3, 4 Patterning within cells can extend down to the level of individual proteins and mRNA.⁵,⁶ But how much of the proteome is actually localized with respect to cell polarity axes? Proteomics combined with cellular fractionation7, 8, 9, 10,...
Preprint
Tumor-initiating cells with reprogramming plasticity are thought to be essential for cancer development and metastatic regeneration in many cancers; however, the molecular mechanisms are not fully understood. This study reports that CD81, a tetraspanin protein marker of small extracellular vesicles (exosomes), functions as a binding partner of CD44...
Preprint
Many individual proteins have been identified as having defined positions relative to cell polarity axes, raising the question of what fraction of all proteins may have polarized localizations. We took advantage of the giant ciliate Stentor coeruleus to quantify the extent of polarized localization proteome-wide. This trumpet-shaped unicellular org...
Article
Full-text available
Global and phosphoproteome profiling has demonstrated great utility for the analysis of clinical specimens. One barrier to the broad clinical application of proteomic profiling is the large amount of biological material required, particularly for phosphoproteomics─currently on the order of 25 mg wet tissue weight. For hematopoietic cancers such as...
Article
Full-text available
Tandem mass spectrometry (MS/MS)-based phosphoproteomics is a powerful technology for global phosphorylation analysis. However, applying four computational pipelines to a typical mass spectrometry (MS)-based phosphoproteomic dataset from a human cancer study, we observed a large discrepancy among the reported phosphopeptide identification and phosp...
Article
Full-text available
Cancers are caused by accumulated DNA mutations. This recognition of the central role of mutations in cancer and recent advances in next‐generation sequencing, has initiated the massive screening of clinical samples and the identification of 1000s of cancer‐associated gene mutations. However, proteomic analysis of the expressed mutation products la...
Article
Full-text available
Global quantification of protein abundances in single cells could provide direct information on cellular phenotypes and complement transcriptomics measurements. However, single-cell proteomics is still immature and confronts many technical challenges. Herein we describe a nested nanoPOTS (N2) chip to improve protein recovery, operation robustness,...
Article
Full-text available
Despite the successful application of tandem mass tags (TMT) for peptide quantitation, missing reporter ions in higher energy collisional dissociation (HCD) spectra remains a challenge for consistent quantitation, especially for peptides with labile post-translational modifications. Ultraviolet photodissociation (UVPD) is an alternative ion activat...
Article
Full-text available
Identifying genomic alterations of cancer proteins has guided the development of targeted therapies, but proteomic analyses are required to validate and reveal new treatment opportunities. Herein, we develop a new algorithm, OPPTI, to discover overexpressed kinase proteins across 10 cancer types using global mass spectrometry proteomics data of 1,0...
Preprint
Full-text available
Despite advances in proteomic technologies, clinical translation of plasma biomarkers remains low, partly due to a major bottleneck between the discovery of candidate biomarkers and downstream costly clinical validation studies. Due to a dearth of multiplexable assays, generally only a few candidate biomarkers are tested, and the validation success...
Article
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphopr...
Article
Recent advances in sample preparation enable label-free mass spectrometry (MS)-based proteome profiling of small numbers of mammalian cells. However, specific devices are often required to downscale sample processing volume from the standard 50-200 μL to sub-μL for effective nanoproteomics, which greatly impedes the implementation of current nanopr...
Article
Full-text available
Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing t...
Article
Full-text available
Despite wide use of anti-vascular endothelial growth factor (VEGF) therapy for many solid cancers, most individuals become resistant to this therapy, leading to disease progression. Therefore, new biomarkers and strategies for blocking adaptive resistance of cancer to anti-VEGF therapy are needed. As described here, we demonstrate that cancer-deriv...
Article
Full-text available
Glioblastoma (GBM) is the most aggressive nervous system cancer, with median survival under 2 years. Understanding its molecular pathogenesis is crucial for improving diagnosis and treatment. We performed an integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs. We identified key...
Conference Paper
Introduction: Breast cancer (BC) is the second most common cause of cancer death among women in the USA. Recent proteogenomic studies of human BC have identified many potential therapeutic biomarkers for the most common types of BC. Here, we strive to comprehensively understand the proteogenomic landscape of difficult-to-treat breast cancer (DTBC)...
Conference Paper
Glioblastoma (GBM) is the most aggressive nervous system cancer, with median survival under 2 years. Understanding its molecular pathogenesis is crucial for improving diagnosis and treatment. We performed an integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs. We identified key...
Article
Our study details the stepwise evolution of gilteritinib resistance in FLT3-mutated acute myeloid leukemia (AML). Early resistance is mediated by the bone marrow microenvironment, which protects residual leukemia cells. Over time, leukemia cells evolve intrinsic mechanisms of resistance, or late resistance. We mechanistically define both early and...
Chapter
Protein phosphorylation is a critical posttranslational modification (PTM), with cell signaling networks being tightly regulated by protein phosphorylation. Despite recent technological advances in reversed-phase liquid chromatography (RPLC)-mass spectrometry (MS)-based proteomics, comprehensive phosphoproteomic coverage in complex biological syste...
Article
Full-text available
Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs))....
Article
In acute myeloid leukemia (AML), activating mutations in FLT3 are the most common genetic abnormality. Multiple FLT3 inhibitors have been developed, including the FDA-approved inhibitor gilteritinib. However, AML patients only respond to gilteritinib for approximately 6 months due to the emergence of drug resistance. While gilteritinib eliminates b...
Article
Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events...
Article
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity...
Article
Protein analysis of small numbers of human cells is primarily achieved by targeted proteomics with antibody-based immunoassays, which have inherent limitations (e.g., low multiplex and unavailability of antibodies for new proteins). Mass spectrometry (MS)-based targeted proteomics has emerged as an alternative because it is antibody-free, high mult...
Article
Multiple myeloma (MM) is a hematological cancer of the antibody-secreting plasma cells. Despite therapeutic advancements, MM remains incurable due to high incidence of drug-resistant relapse. In recent years, targeted immunotherapies, which take advantage of the immune system's cytotoxic defenses to specifically eliminate tumor cells expressing cer...
Article
Activating mutations in the tyrosine kinase receptor FLT3 are observed in ~35% of all acute myeloid leukemia (AML) cases. Multiple FLT3 inhibitors are currently in clinical development and while most patients initially respond well to FLT3 inhibition, resistance inevitably develops in a period of months. During the initial response to FLT3 inhibito...
Article
Full-text available
The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics...
Article
Full-text available
We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16...
Article
Full-text available
Extracellular vesicles (EVs) are released by nearly all cell types as part of normal cell physiology, transporting biological cargo, including nucleic acids and proteins, across the cell membrane. In pathological states such as cancer, EV-derived cargo may mirror the altered state of the cell of origin. Exosomes are the smaller, 50–150 nanometer-si...
Conference Paper
p>Endometrial cancer (EC) is the sixth most common cancer in women globally and is one of the few cancers for which mortality is increasing; to address the need to develop new methods for the diagnosis and treatment of this disease, we performed a comprehensive proteogenomic characterization of 95 endometrial carcinomas. We prospectively collected...
Conference Paper
Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept...
Conference Paper
High-grade serous cancer (HGSC), the most prevalent histotype of ovarian cancer, has the lowest survival rates and is the leading cause of gynecological cancer-related deaths in the developed world. HGSC is characterized by the presence of nearly universal mutations, diverse and widespread chromosomal instability, and a general shortage of targetab...
Conference Paper
Mass Spectrometry based proteomics profiling has become a powerful tool for broad quantification of proteins and their post-translational modifications for cancer research. Due to extensive efforts in the field to benchmark and standardize complex workflows, particularly those of the Clinical Proteomics Tumor Analysis Consortium (CPTAC), proteomics...
Conference Paper
Dysregulated oncogenic signaling is a key hallmark of cancer. Protein kinase alterations, including genomic mutations and copy-number amplifications, are known druggable targets in multiple cancer types. Thus, kinase inhibitor drugs act on protein and direct observation of protein/phospho-level overexpression may reveal new treatment opportunities....
Preprint
Full-text available
Background: Global and phosphoproteome profiling has demonstrated great utility for the analysis of clinical specimens. One major barrier to the broad clinical application of proteomic profiling is the large amount of biological material required, particularly for phosphoproteomics—currently on the order of 25 mg wet tissue weight, depending on tis...
Preprint
Full-text available
Background: Global and phosphoproteome profiling has demonstrated great utility for the analysis of clinical specimens. One major barrier to the broad clinical application of proteomic profiling is the large amount of biological material required, particularly for phosphoproteomics—currently on the order of 25 mg wet tissue weight, depending on tis...
Article
Single-cell proteomics can provide critical biological insight into the cellular heterogeneity that is masked by bulk-scale analysis. We have developed a nanoPOTS (nanodroplet processing in one pot for trace samples) platform and demonstrated its broad applicability for single-cell proteomics. However, because of nanoliter-scale sample volumes, the...
Article
Background: Approximately 85% of the United States military active duty population is male and less than 50 years of age with elevated levels of known risk factors for oropharyngeal squamous cell carcinoma (OPSCC) include smoking, excessive use of alcohol, and greater numbers of sexual partners and elevated prevalence of human papilloma virus (HPV...
Article
Full-text available
Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes,...
Article
Full-text available
In the absence of a dominant driving mutation other than uniformly present TP53 mutations, deeper understanding of the biology driving ovarian high-grade serous cancer (HGSC) requires analysis at a functional level, including post-translational modifications. Comprehensive proteogenomic and phosphoproteomic characterization of 83 prospectively coll...
Article
Full-text available
Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept...
Article
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition,...
Article
(Cell 179, 964–983.e1–e31; October 31, 2019) In the originally published version of this article, Daniel Geiszler's last name was misspelled. This error has now been corrected in the article online.
Article
Multiple myeloma (MM) is a disease defined by clonal proliferation of abnormal plasma cells from B-cells. Improved treatments for MM have led to improving overall lifespan, but still remains incurable due to acquired resistance to therapy and tumor heterogeneity. Single-cell RNA sequencing studies (scRNA-seq) of MM patients have highlighted the sig...
Article
Effective extension of mass spectrometry-based proteomics to single cells remains challenging. Herein we combined microfluidic nanodroplet technology with tandem mass tag (TMT) isobaric labeling to significantly improve analysis throughput and proteome coverage for single mammalian cells. Isobaric labeling facilitated multiplex analysis of single c...
Article
Protein phosphorylation is a critical post-translational modification (PTM). Despite recent technological advances in reversed-phase liquid chromatography (RPLC)-mass spectrometry (MS)-based proteomics, comprehensive phosphoproteomic coverage in complex biological systems remains challenging, especially for hydrophilic phosphopeptides with enriched...
Article
Full-text available
Each year, thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possi...
Conference Paper
Introduction: Although many (~40%) of the screen-detected prostate cancers are indolent (Gleason Score <= 6) and pose minimal risk for progression, advanced stage prostate cancer is a lethal disease with 5-year survival rates around 29%. The challenge is to identify biomarkers for early detection of aggressive disease, when the cancer is still orga...
Conference Paper
The Department of Defense Serum Repository (DODSR) represents a unique resource enabling longitudinal studies of cancer risk, progression, and response to therapy. The DODSR was initiated in 1989, initially as a means for HIV surveillance, and is comprised of serum samples from active and reserve military personnel drawn at enlistment and annually...
Conference Paper
Full-text available
We prospectively collected matched tumor specimens, adjacent non-tumor tissues, and blood samples from 110 colon cancer patients and analyzed the samples using seven omics platforms, including whole-exome sequencing, copy number arrays, RNA-Seq, miRNA-Seq, label-free global proteomics, isobaric tandem mass tag (TMT) labeling-based global proteomics...
Conference Paper
The Department of Defense Serum Repository (DODSR) represents a unique resource enabling longitudinal studies of cancer risk, progression, and response to therapy. The DODSR was initiated in 1989, initially as a means for HIV surveillance, and is comprised of serum samples from active and reserve military personnel drawn at enlistment and annually...
Conference Paper
We prospectively collected matched tumor specimens, adjacent non-tumor tissues, and blood samples from 110 colon cancer patients and analyzed the samples using seven omics platforms, including whole-exome sequencing, copy number arrays, RNA-Seq, miRNA-Seq, label-free global proteomics, isobaric tandem mass tag (TMT) labeling-based global proteomics...
Conference Paper
p>A major challenge in lung cancer prevention and cure hinges on identifying the at-risk population who ultimately develops lung cancer. Previously we reported proteomic alterations in the cytologically normal bronchial epithelial cells collected from the bronchial brushings of individuals at-risk for lung cancer. Proteins were identified by shotgu...
Conference Paper
Introduction: Although many (~40%) of the screen-detected prostate cancers are indolent (Gleason Score <= 6) and pose minimal risk for progression, advanced stage prostate cancer is a lethal disease with 5-year survival rates around 29%. The challenge is to identify biomarkers for early detection of aggressive disease, when the cancer is still orga...
Article
Two-dimensional reversed-phase capillary liquid chromatography (2D RPLC) separations have enabled comprehensive proteome profiling of biological systems. However, milligram sample quantities of proteins are typically required due to significant losses during offline fractionation. Such large sample requirement generally precludes the application sa...

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