A5065361795- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- HER2/EGFR in Cancer Research
- Metabolomics and Mass Spectrometry Studies
- Medical Imaging Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Bioinformatics and Genomic Networks
- SARS-CoV-2 detection and testing
- Analytical Chemistry and Chromatography
- Retinoids in leukemia and cellular processes
- Sepsis Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Bacterial Identification and Susceptibility Testing
- Machine Learning in Healthcare
- Cancer, Lipids, and Metabolism
- Gene expression and cancer classification
- Peptidase Inhibition and Analysis
- Artificial Intelligence in Healthcare
- Radiomics and Machine Learning in Medical Imaging
- COVID-19 Clinical Research Studies
- Protein Kinase Regulation and GTPase Signaling
- Glaucoma and retinal disorders
Astellas Pharma (United States)
2016
Cedars-Sinai Medical Center
2008-2012
Stanford University
2012
Fred Hutch Cancer Center
2008-2012
University of Southern California
2012
University of California, Los Angeles
2008
Amgen (United States)
1997-2001
Ludwig Cancer Research
1992
The proteome of normal male urine from a commercial pooled source has been examined using direct liquid chromatography-tandem mass spectrometry (LC-MS/MS). entire urinary protein mixture was denatured, reduced and enzymatically digested prior to LC-MS/MS analysis hybrid-quadrupole time-of-flight spectrometer (Q-TOF) perform data-dependent ion selection fragmentation. To fragment as many peptides possible, the analyzed four separate times, with selecting ions for fragmentation subset range...
Improved identification of bacterial and viral infections would reduce morbidity from sepsis, antibiotic overuse, lower healthcare costs. Here, we develop a generalizable host-gene-expression-based classifier for acute infections. We use training data (N = 1069) 18 retrospective transcriptomic studies. Using only 29 preselected host mRNAs, train neural-network with bacterial-vs-other area under the receiver-operating characteristic curve (AUROC) 0.92 (95% CI 0.90-0.93) viral-vs-other AUROC...
AGS-16C3F is an antibody-drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma. and other ADCs have been reported to cause ocular toxicity patients by unknown mechanisms. To investigate this toxicity, we developed vitro assay using human corneal epithelial cells (HCEC) show that HCECs internalized macropinocytosis, causing inhibition proliferation....
The fibroblast growth factors (FGFs) play key roles in controlling tissue growth, morphogenesis, and repair animals. We have cloned a novel member of the FGF family, designated FGF-18, that is expressed primarily lungs kidneys at lower levels heart, testes, spleen, skeletal muscle, brain. Sequence comparison indicates FGF-18 highly conserved between humans mice most homologous to FGF-8 among family members. has typical signal sequence was glycosylated secreted when it transfected into...
The classical minor lymphocyte stimulating (Mls) antigens, which induce a strong primary T cell response in vitro, are closely linked to endogenous copies of mouse mammary tumor viruses (MMTV). Expression Mls genes leads clonal deletion subsets expressing specific receptor (TCR) V beta chains. We describe the isolation and characterization new exogenous (infectious) MMTV with biological properties similar antigen Mls-1a. In vivo administration either Mls-1a-expressing B cells or infectious...
With an emphasis on obtaining a multitude of high quality tandem mass spectrometry spectra for protein identification, instrumental parameters are described the liquid chromatography-tandem analysis trypsin digested unfractionated urine using hybrid quadrupole-time-of-flight (Q-TOF) spectrometer. Precursor acquisition rates up to 20 distinct precursors/minute in single were obtained through use parallel precursor selection (four precursors/survey period) and variable collision induced...
OBJECTIVES: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As result limitations in current diagnostics, guidelines recommend early antimicrobials for suspected patients to improve outcomes at cost antimicrobial stewardship. We aimed develop prospectively validate new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) determine the likelihood bacterial viral infections. DESIGN: Prospective...
Background and importance mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid accurate prediction of severity in patients with suspected acute infections remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed predict disease infection or sepsis. Objective Validation host-mRNA IMX-SEV-2. Design, settings participants Prospective, observational, convenience cohort emergency department (ED) infections....
Abstract The success of the mass spectrometric‐based approaches for identification gel‐separated proteins relies upon recovery peptides, without high levels ionization‐suppressing contaminants, in solvents compatible with spectrometer being employed. We sought to determine whether in‐gel or on‐membrane digestion provided a significant advantage when low sub‐pmol quantities were analyzed by matrix‐assisted laser‐desorption/ionization spectrometry (MALDI‐MS) respect number and size released...
Mass spectrometry-based proteomics experiments have become an important tool for studying biological systems. Identifying the proteins in complex mixtures by assigning peptide fragmentation spectra to sequences is step process. The 1−2 ppm mass-accuracy of hybrid instruments, like LTQ-FT, has been cited as a key factor their ability identify larger number peptides with greater confidence than competing instruments. However, replicate 18-protein mixture, we note parent masses deviate 171 ppm,...
Abstract Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for viral infections and validate it in independent data, including COVID-19. We developed logistic regression-based validated multiple infection settings used training data (N = 705) from 21 retrospective transcriptomic clinical studies influenza other illnesses looking at preselected panel host immune response messenger RNAs. selected 6 RNAs...
The current paradigm for protein identification using mass spectrometric derived peptide-mass and fragment-ion data employs computer algorithms which match uninterpreted or partially interpreted to sequence databases, both translated nucleotide databases. Nucleotide databases continue grow at a rapid rate some species, providing an unsurpassed resource in those species. Ion-trap spectrometers with their ability rapidly generate spectra data-dependent manner high sensitivity accuracy has led...
A DNA/protein sequence comparison is a popular computational tool for molecular biologists. Finding good alignment implies an evolutionary and/or functional relationship between proteins or genomic loci. Sequential similarity two indicates their structural resemblance, providing practical approach modeling, when structure of one these known. The first step in the homology modeling construction accurate alignment. commonly used algorithms do not provide adequate treatment structurally...
Abstract Clinical oncology is hampered by lack of tools to accurately assess a patient's response pathway-targeted therapies. Serum and tumor cell surface proteins whose abundance, or change in abundance therapy, differentiates patients responding therapy from not could be usefully incorporated into for monitoring response. Here, we posit then verify that proteomic discovery vitro tissue culture models can identify with concordant vivo behavior further, valuable approach identifying...
Abstract FLT3 is a member of the class III receptor tyrosine kinase family that includes C-KIT, C-FMS and platelet derived growth factor (PDGFR). primarily expressed in early myeloid lymphoid progenitors plays an important role their proliferation differentiation. In human leukemia, on 70-90% acute leukemia (AML) most B-acute lymphoblastic (B-ALL). genetic aberrations are commonly detected patients with AML. The common aberration internal tandem duplication (ITD), which occurs 25-30% AML...
The proteome of normal male urine from a commercial pooled source has been examined using direct liquid chromatography-tandem mass spectrometry (LC-MS/MS). entire urinary protein mixture was denatured, reduced and enzymatically digested prior to LC-MS/MS analysis hybrid-quadrupole time-of-flight spectrometer (Q-TOF) perform data-dependent ion selection fragmentation. To fragment as many peptides possible, the analyzed four separate times, with selecting ions for fragmentation subset range...
Abstract Background Determining the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for viral infections and validate it in independent data, including COVID-19. Methods We developed validated multiple infection settings used training data (N=705) from 21 retrospective transcriptomic clinical studies influenza other illnesses looking at preselected panel host immune response messenger RNAs. Results selected 6 RNAs...
Abstract Background While major progress has been made to establish diagnostic tools for the diagnosis of SARS-CoV-2 infection, determining severity COVID-19 remains an unmet medical need. With limited hospital resources, gauging would allow some patients safely recover in home quarantine while ensuring sicker get needed care. We discovered a 5 host mRNA-based classifier influenza and other acute viral infections validated from Greece. Methods used training data (N=705) 21 retrospective...
With an emphasis on obtaining a multitude of high quality tandem mass spectrometry spectra for protein identification, instrumental parameters are described the liquid chromatography-tandem analysis trypsin digested unfractionated urine using hybrid quadrupole-time-of-flight (Q-TOF) spectrometer. Precursor acquisition rates up to 20 distinct precursors/minute in single were obtained through use parallel precursor selection (four precursors/survey period) and variable collision induced...
Acute infection, if not rapidly and accurately detected, can lead to sepsis, organ failure even death. Current detection of acute infection as well assessment a patient's severity illness are imperfect. Characterization immune response by quantifying expression levels specific genes from blood represents potentially more timely precise means accomplishing both tasks. Machine learning methods provide platform leverage this host for development deployment-ready classification models....