A5059260959- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Antimicrobial Resistance in Staphylococcus
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Analytical Chemistry and Chromatography
- Mass Spectrometry Techniques and Applications
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Free Radicals and Antioxidants
- Environmental Chemistry and Analysis
- Antibiotic Resistance in Bacteria
- Steroid Chemistry and Biochemistry
- Antioxidant Activity and Oxidative Stress
- Antimicrobial Peptides and Activities
- Hedgehog Signaling Pathway Studies
- Analytical Methods in Pharmaceuticals
- Lipid Membrane Structure and Behavior
- Advanced Proteomics Techniques and Applications
- interferon and immune responses
- Receptor Mechanisms and Signaling
- Bacterial Genetics and Biotechnology
- Bacterial biofilms and quorum sensing
- Streptococcal Infections and Treatments
- Bacterial Identification and Susceptibility Testing
University of Washington
2016-2025
Northeastern University
2023-2025
Children's Hospital of Zhejiang University
2025
East China University of Science and Technology
2021-2024
Seattle University
2024
University of Idaho
2019-2021
Vanderbilt University
2009-2017
Massachusetts General Hospital
2016
Nashville Oncology Associates
2014
University of Illinois Chicago
2004-2010
Collision cross section (CCS) measurement of lipids using traveling wave ion mobility-mass spectrometry (TWIM-MS) is high interest to the lipidomics field. However, currently available calibrants for CCS TWIM are predominantly peptides that display quite different physical properties and gas-phase conformations from lipids, which could lead large calibration errors lipids. Here we report direct a series phosphatidylcholines (PCs) phosphatidylethanolamines (PEs) in nitrogen drift tube...
Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs ubiquitously used in medical settings, restaurants, and homes as cleaners disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified mice, resulted developmental, reproductive, immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, disruption of...
Finding relevant chemicals in the vast (known) chemical space is a major challenge for environmental and exposomics studies leveraging nontarget high resolution mass spectrometry (NT-HRMS) methods. Chemical databases now contain hundreds of millions chemicals, yet many are not relevant. This article details an extensive collaborative, open science effort to provide dynamic collection environmental, metabolomics, research, along with supporting information about their relevance assist...
Rate constants for autoxidation propagation of several unsaturated lipids in benzene solution at 37 °C and phosphatidylcholine liposomes were determined by a linoleate radical clock. This clock is based on competition between hydrogen atom abstraction an intermediate peroxyl derived from linoleic acid that leads to trans,cis-conjugated hydroxyoctadecadienoic product β-fragmentation the same gives trans,trans-product acid. this approach relative (kp = 62 M−1 s−1) were: arachidonic 197 ± 13...
Free radical chain oxidation of highly oxidizable 7-dehydrocholesterol (7-DHC), initiated by 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile), was carried out at 37 °C in benzene for 24 h. Fifteen oxysterols derived from 7-DHC were isolated and characterized with 1D 2D NMR spectroscopy mass spectrometry. A mechanism that involves abstraction hydrogen atoms C-9 and/or C-14 is proposed to account the formation all reaction progress profile. In either H-9 or H-14 mechanism, a pentadienyl...
Smith-Lemli-Opitz syndrome (SLOS) is a metabolic and developmental disorder caused by mutations in the gene encoding enzyme 7-dehydrocholesterol reductase (Dhcr7). This catalyzes last step cholesterol biosynthesis, levels of (7-DHC), substrate for this enzyme, are elevated SLOS patients as result defect. Our group has previously shown that 7-DHC extremely prone to free radical autoxidation, we identified about dozen different oxysterols formed from oxidation 7-DHC. We report here...
Ion mobility-mass spectrometry (IM-MS) can provide orthogonal information, i.e., m/z and collision cross section (CCS), for the identification of drugs drug metabolites. However, only a small number CCS values are available drugs, which limits use as an parameter assessment structure–function relationships using IM-MS. Here, we report development rapid workflow measurement large or drug-like molecules in nitrogen on widely traveling wave IM-MS (TWIM-MS) platform. Using combination molecule...
Identification of unknowns is a bottleneck for large-scale untargeted analyses like metabolomics or drug metabolite identification. Ion mobility-mass spectrometry (IM-MS) provides rapid two-dimensional separation ions based on their mobility through neutral buffer gas. The an ion related to its collision cross section (CCS) with the gas, physical property that determined by size and shape ion. This structural dependency makes CCS promising characteristic compound identification, but this...
Previous work suggests that altered lipid metabolism may be associated with daptomycin resistance in Gram-positive pathogens, but lipidomic changes underlying are not fully understood. We performed untargeted lipidomics by using three-dimensional hydrophilic interaction liquid chromatography-ion mobility-mass spectrometry (HILIC-IM-MS) to characterize alterations the lipidomes of daptomycin-susceptible and -resistant isogenic strain pairs Enterococcus faecalis, Staphylococcus aureus,...
Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report combination hydrophilic-interaction liquid chromatography (HILIC) with traveling-wave IM-MS (TWIM-MS) comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, glycerophospholipids are separated on basis their backbones in IM dimension, whereas subclasses each category mostly headgroups HILIC...
Transcriptional rates are often estimated by fitting the distribution of mature mRNA numbers measured using smFISH (single molecule fluorescence in situ hybridization) with predicted telegraph model gene expression, which defines two promoter states activity and inactivity. However, fluctuations strongly affected processes downstream transcription. In addition, assumes one copy but experiments, cells may have copies as replicate their genome during cell cycle. While it is presumed that...
Ferroptosis is a form of regulated cell death driven by lipid peroxidation polyunsaturated fatty acids (PUFAs). Lipid can propagate through either the hydrogen-atom transfer (HAT) or peroxyl radical addition (PRA) mechanism. However, contribution PRA mechanism to induction ferroptosis has not been studied. In this study, we aim elucidate relationship between reactivity and mechanisms induction. We found that while some peroxidation-reactive lipids, such as 7-dehydrocholesterol, vitamins D
The COVID-19 pandemic has led to significantly increased human exposure the widely used disinfectants quaternary ammonium compounds (QACs). Xenobiotic metabolism serves a critical role in clearance of environmental molecules, yet limited data are available on routes QAC or metabolite levels humans. To address this gap and advance biomonitoring capabilities, we analyzed 19 commonly QACs their phase I metabolites by liquid chromatography–ion mobility–tandem mass spectrometry (LC–IM–MS/MS). In...
The level of 7-dehydrocholesterol (7-DHC) is elevated in tissues and fluids Smith-Lemli-Opitz syndrome (SLOS) patients due to defective 7-DHC reductase. Although over a dozen oxysterols have been identified from free radical oxidation solution, oxysterol profiles SLOS cells never studied. We report here the identification complete characterization novel oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), as biomarker for fibroblasts brain tissue mouse model. Deuterated (d7)-standards DHCEO...
7-Ketocholesterol is a bioactive sterol, potent competitive inhibitor of cytochrome P450 7A1, and toxic in liver cells. Multiple origins this compound have been identified, with cholesterol being the presumed precursor. Although routes for formation 7-keto from established, we found that 7-dehydrocholesterol (the immediate precursor cholesterol) oxidized by 7A1 to 7-ketocholesterol (k(cat)/K(m) = 3 × 10(4) m(-1) s(-1)). converted lathosterol (Δ(5)-dihydro-7-dehydrocholesterol) mixture...
Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive; thus, potentially novel techniques - including human microphysiological systems, or "organs chips" proposed to accelerate drug predict safety. Polymyxins potent antibiotics against multidrug-resistant microorganisms; however, remains restricted because high risk...
Cellular lipids are speculated to act as key intermediates in Hedgehog signal transduction, but their precise identity and function remain enigmatic. In an effort identify such lipids, we pursued a pathway inhibitory activity that is particularly abundant flagellar of Chlamydomonas reinhardtii, resulting the purification identification ergosterol endoperoxide, B-ring oxysterol. A mammalian analog ergosterol, 7-dehydrocholesterol (7-DHC), accumulates Smith-Lemli-Opitz syndrome, human genetic...