A5003828326- Cholesterol and Lipid Metabolism
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Estrogen and related hormone effects
- Drug Transport and Resistance Mechanisms
- Sphingolipid Metabolism and Signaling
- Hormonal Regulation and Hypertension
- Mitochondrial Function and Pathology
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Steroid Chemistry and Biochemistry
- Atherosclerosis and Cardiovascular Diseases
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Liver Disease Diagnosis and Treatment
- Advanced Proteomics Techniques and Applications
- Dermatology and Skin Diseases
- Gut microbiota and health
- Lipid Membrane Structure and Behavior
- Hedgehog Signaling Pathway Studies
- Inflammasome and immune disorders
- Diet and metabolism studies
The University of Texas Southwestern Medical Center
2016-2025
Southwestern Medical Center
2007-2025
HumanN (United States)
2019-2024
Yale University
2021-2024
Adelphi Laboratory Center
2014-2023
Southwestern University
2023
Center for Human Genetics
2009-2021
University of Minnesota
2001-2021
Hormel (United States)
2021
Saint Louis University
2020
The focus of the present study was to define human plasma lipidome and establish novel analytical methodologies quantify large spectrum lipids. Partial lipid analysis is now a regular part every patient's blood test physicians readily regularly prescribe drugs that alter levels major lipids such as cholesterol triglycerides. Plasma contains many thousands distinct molecular species fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids,...
Abstract Oncogenes influence nutrient metabolism and dependence. The oncogene c-Myc stimulates glutamine renders cells dependent on to sustain viability (“glutamine addiction”), suggesting that treatments targeting might selectively kill c-Myc–transformed tumor cells. However, many current or proposed cancer therapies interfere with the of glucose, not glutamine. Here, we studied how maintained when glucose was impaired. In SF188 glioblastoma cells, deprivation did affect net utilization but...
Type I interferon (IFN) protects against viruses, yet it also has a poorly understood suppressive influence on inflammation. Here, we report that activated mouse macrophages lacking the IFN-stimulated gene cholesterol 25-hydroxylase (Ch25h) and are unable to produce oxysterol 25-hydroxycholesterol (25-HC) overproduce inflammatory interleukin-1 (IL-1) family cytokines. 25-HC acts by antagonizing sterol response element-binding protein (SREBP) processing reduce Il1b transcription broadly...
To date, estrogen is the only known endogenous receptor (ER) ligand that promotes ER+ breast tumor growth. We report cholesterol metabolite 27-hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, cancer patients, 27HC content normal tissue increased compared to cancer-free controls, and further elevated. Increased correlated with diminished expression of CYP7B1, metabolizing enzyme, reduced CYP7B1 tumors associated poorer patient survival. Moreover,...
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, steatohepatitis (NASH), and cirrhosis. Recognition timely diagnosis these different stages, particularly NASH, is important for both potential reversibility limitation complications. Liver biopsy remains the clinical standard definitive diagnosis. Diagnostic tools minimizing need invasive procedures or that add information to histologic data are in novel management strategies growing epidemic NAFLD. We describe an...
25-Hydroxycholesterol is produced in mammalian tissues. The function of this oxysterol unknown. Here we describe a central role for 25-hydroxycholesterol regulating the immune system. In initial experiments, found that stimulation macrophage Toll-like receptors (TLR) induced expression cholesterol 25-hydroxylase and synthesis 25-hydroxycholesterol. Treatment naïve B cells with nanomolar concentrations suppressed IL-2-mediated cell proliferation, repressed activation-induced cytidine...
Significance The absence in the Protein Data Bank of full-length structures bitopic membrane proteins with one transmembrane helix, probably because difficulties ordered crystallization, has limited understanding how single-transmembrane helices orient enzymes and sensors at bilayer surface. X-ray crystal yeast lanosterol 14α-demethylase, a cytochrome P450, show helix spanning single may lead to constraints on orientation putative substrate entry portal from within bilayer. also locate...
KRAS is one of the most commonly mutated oncogenes in human cancer. Mutant aberrantly regulates metabolic networks. However, contribution cellular metabolism to mutant tumorigenesis not completely understood. We report that intracellular fatty acid through Acyl-coenzyme A (CoA) synthetase long-chain family member 3 (ACSL3), which converts acids into Acyl-CoA esters, substrates for lipid synthesis and β-oxidation. ACSL3 suppression associated with depletion ATP causes death lung cancer cells....
We describe the development of a method for extraction and analysis 62 sterols, oxysterols, secosteroids from human plasma using combination HPLC-MS GC-MS. Deuterated standards are added to 200 μl plasma. Bulk lipids extracted with methanol:dichloromethane, sample is hydrolyzed novel procedure, sterols isolated solid-phase (SPE). Compounds resolved on C18 core-shell HPLC columns by GC. Sterols oxysterols measured triple quadrupole mass spectrometers, lathosterol Detection each compound was ∪...
Abstract Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, role of FA LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate FASN, rate-limiting enzyme synthesis, while being dispensable EGFR-mutant or wild-type LC, required for viability cells. Integrating lipidomic, transcriptomic functional analyses,...
Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triglyceride (TG) synthesis. DGAT2 deletion in mice lowers liver TGs, and inhibitors are under investigation for treatment fatty disease. Here, we show that inhibition also suppressed SREBP-1 cleavage, reduced acid synthesis, lowered TG accumulation secretion from liver. increased phosphatidylethanolamine (PE) levels endoplasmic reticulum (ER) inhibited while overexpression ER PE concentrations cleavage vivo. enrichment...
Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 ( NCOA7 ) deficiency endothelium produced an oxysterol bile acid signature through dysregulation, promoting pathophenotypes. This overlapped with a plasma metabolite associated human mortality. Mice deficient for...