- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Mass Spectrometry Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Protease and Inhibitor Mechanisms
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Clusterin in disease pathology
- Ubiquitin and proteasome pathways
- Prostate Cancer Treatment and Research
- Cancer Research and Treatments
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Analytical Chemistry and Chromatography
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Lipid metabolism and disorders
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Machine Learning in Bioinformatics
- Advanced Biosensing Techniques and Applications
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
Stanford University
2016-2025
Stratford University
2022-2025
Palo Alto University
2013-2025
Stanford Medicine
2019-2025
Eindhoven Cancer Registry
2022
University College London
2022
University of York
2022
Newcastle University
2022
Howard Hughes Medical Institute
2017
University of Utah
2017
Circulating tumor-derived extracellular vesicles (EVs) have emerged as a promising source for identifying cancer biomarkers early detection. However, the clinical utility of EVs has thus far been limited by fact that most EV isolation methods are tedious, nonstandardized, and require bulky instrumentation such ultracentrifugation (UC). Here, we report size-based tool called ExoTIC (exosome total chip), which is simple, easy-to-use, modular, facilitates high-yield high-purity from biofluids....
The natural microenvironment of tumors is composed extracellular matrix (ECM), blood vasculature, and supporting stromal cells. physical characteristics ECM as well the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, differentiation. To mimic tumor outside human body for drug testing, two-dimensional (2-D) murine models are routinely used. Although these conventional approaches employed preclinical studies, they still present challenges....
Chromatin looping is key to gene regulation, yet no broadly applicable methods selectively modify chromatin loops have been described. We engineered a method for loop reorganization using CRISPR-dCas9 (CLOuD9) and reversibly establish loops. demonstrate the power of this technology modulate expression at targeted loci.
MicroRNAs are critical regulators of cancer initiation, progression, and dissemination. Extensive evidence suggests that the inhibition over-expressed oncogenic miRNA function can be a robust strategy for anticancer therapy. However, in vivo targeted delivery therapeutics to various types cancers remains major challenge. Inspired by their natural synthesis cargo capabilities, researchers have exploited tumor cell-derived extracellular vesicles (TEVs) cancer-targeted theranostics. Here, we...
Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), deubiquitinating enzyme, is elevated in tissues plasma from patients with carcinomas. Loss of UCHL1 decreases tumor growth inhibits metastasis these malignancies. maintains differentiation promotes progression by regulating nucleoporin, POM121, p53. binds, deubiquitinates,...
Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in identification protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models cancer been shown to faithfully recapitulate molecular, biological, clinical features disease. Here, we sought exploit merits a well-characterized GEM model pancreatic determine whether proteomics technologies allow development such are relevant cancer. Methods...
Graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation, affects skin, liver, and gastrointestinal tract. There are no plasma biomarkers specific for any acute GVHD target organ. We used a large-scale quantitative proteomic discovery procedure to identify biomarker candidates skin validated lead candidate, elafin, with enzyme-linked immunosorbent assay in samples from 492 patients. Elafin was overexpressed biopsies. Plasma concentrations elafin were...
Glycosylation is an important post-translational modification. Analysis of glycopeptides difficult using collision-induced dissociation, as it typically yields only information about the glycan structure, without any peptide sequence information. We demonstrate here how a 3D-quadrupole ion trap, complementary techniques collision induced dissociation (CID) and electron-transfer (ETD), can be used to elucidate structure N-glycosylated from fractionated tryptic digest lectin coral tree,...
We have implemented a high throughput platform for quantitative analysis of serum autoantibodies, which we applied to lung cancer discovery novel antigens and validation in prediagnostic sera autoantibodies previously defined based on collected at the time diagnosis.Proteins from human adenocarcinoma cell line A549 lysates were subjected extensive fractionation. The resulting 1,824 fractions spotted duplicate nitrocellulose-coated slides. microarrays produced used blinded study determine...
In-depth analysis of the serum and plasma proteomes by mass spectrometry is challenged vast dynamic range protein abundance substantial complexity. There merit in reducing complexity through fractionation to facilitate low-abundance proteins. However, reduces throughput has potential diluting individual proteins or inducing their loss. Here, we have investigated contribution extensive intact depth analysis. Pooled depleted abundant was fractionated an orthogonal two-dimensional system...
Post-translational modifications (PTMs) on proteins often function to regulate signaling cascades, with the activation of T cells during an adaptive immune response being a classic example. Mounting evidence indicates that modification by O-linked N-acetylglucosamine (O-Glcnac), only mammalian glycan found nuclear and cytoplasmic proteins, helps cell activation. Yet, mechanistic understanding how O-Glcnac functions in remains elusive, partly because difficulties mapping quantifying sites....
The discovery of breast cancer associated plasma/serum biomarkers is important for early diagnosis, disease mechanism elucidation, and determination treatment strategy the disease. In this study serum samples, a multidimensional fractionation platform combined with mass spectrometric analysis were used to achieve identification medium lower abundance proteins, as well simultaneously detect glycan changes. Immuno-affinity depletion multi-lectin chromatography (M-LAC) integrated into an...
Significance NEPC is a highly aggressive subtype of prostate cancer that increasing in incidence, likely due to use new secondary androgen deprivation therapies. Here, we demonstrate Trop2 significantly elevated CRPC and represents driver metastatic NEPC. overexpression increases tumor growth, drives metastasis neuroendocrine phenotype, PARP1 levels. Inhibition Trop2-driven decreases features, colonization vivo, suggesting inhibitors may represent promising therapeutic strategy for...
Background and Aims Vascular invasion (VI) is a critical risk factor for HCC recurrence poor survival. The molecular drivers of vascular in are open investigation. Deciphering the landscape invasive will help identify therapeutic targets noninvasive biomarkers. Approach Results To this end, we undertook study to evaluate genomic, transcriptomic, proteomic profile tumors with VI using multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In TCGA Liver...
Abstract Prostate cancer is the most common in men and it estimated that over 350,000 worldwide die of prostate every year. There remains an unmet clinical need to improve how clinically significant diagnosed develop new treatments for advanced disease. Aberrant glycosylation a hallmark implicated tumour growth, metastasis, immune evasion. One key drivers aberrant dysregulated expression enzymes within cell. Here, we demonstrate using multiple independent cohorts glycosyltransferase enzyme...
Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every type. A common change tumour cell an increase α2,6 sialylation N-glycans, modification driven by the sialyltransferase ST6GAL1. ST6GAL1 overexpressed numerous types, sialylated are fundamental for growth, metastasis, immune evasion, drug resistance, but role prostate poorly understood. Here, we analyse matched normal tissue samples from 200 patients verify that...
Y-box binding protein-1 (YB-1) is a proto-oncogenic protein associated with translation regulation. It plays crucial role in the development and progression of triple-negative breast cancer (TNBC). In this study, we describe promising approach to inhibit YB-1 using SU056, small-molecule inhibitor. SU056 physically interacts reduces its expression, which helps restrain TNBC. Proteome profiling analysis indicates that inhibition by can alter proteins regulate translation, an essential process...
Ion−ion reactions between a variety of peptide cations (doubly and triply charged) SO2 anions have been studied in 3-D quadrupole ion trap, resulting proton electron transfer. Electron transfer dissociation (ETD) gives many c- z-type fragments, extensive sequence coverage the case protonated peptides with SO2•-. For charged neurotensin, which direct comparison can be made linear trap results, abundances ETD fragments relative to one another appear similar. Reactions doubly SO2•- give much...
The ion/ion reactions of several dozen reagent anions with triply protonated cations the model peptide KGAILKGAILR have been examined to evaluate predictions a Landau−Zener-based for likelihood electron transfer. Evidence transfer was provided by appearance fragment ions unique or capture dissociation. Proton and are competitive processes any combination anionic cationic reactants. For in peptides, proton is usually significantly more exothermic than If charge occurs at relatively long...