A5002994981- Protein Kinase Regulation and GTPase Signaling
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Mass Spectrometry Techniques and Applications
- Sphingolipid Metabolism and Signaling
- Calcium signaling and nucleotide metabolism
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Cholesterol and Lipid Metabolism
- Adenosine and Purinergic Signaling
- Metabolism, Diabetes, and Cancer
- PI3K/AKT/mTOR signaling in cancer
- Influenza Virus Research Studies
- Liver Disease Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Neural dynamics and brain function
- Advanced Proteomics Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Microbial Metabolism and Applications
Center for Biologics Evaluation and Research
2023
United States Food and Drug Administration
2023
Vanderbilt University
2009-2021
Vanderbilt University Medical Center
2003-2018
Institute of Chemical Biology and Fundamental Medicine
2010
The Ohio State University
2010
University School of Nashville
2009
Whitehead Institute for Biomedical Research
2009
Brigham and Women's Hospital
2009
Harvard University
2009
Formation of coatomer-coated vesicles from Golgi-enriched membranes requires the activation a small GTP-binding protein, ADP ribosylation factor (ARF). ARF is also an efficacious activator phospholipase D (PLD), activity that relatively abundant on membranes. It has been proposed ARF, which recruited onto cytosolic pools, acts directly to promote coatomer binding and in 3:1 stoichiometry with coated vesicles. We present evidence not necessary for initiating coat assembly Golgi cell lines...
Abstract Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, receptors. A comprehensive analysis lipid molecules, “lipidomics,” in context genomics proteomics is crucial to understanding cellular physiology pathology; consequently, biology has become a major research target postgenomic revolution systems biology. To facilitate international communication about lipids, classification lipids with common platform that compatible...
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...
A genetic variant in PNPLA3 (PNPLA3I148M), a triacylglycerol (TAG) hydrolase, is major risk factor for nonalcoholic fatty liver disease (NAFLD); however, the mechanism underlying this association not known. To develop an animal model of PNPLA3-induced disease, we generated transgenic mice that overexpress similar amounts wild-type (PNPLA3WT) or mutant (PNPLA3I148M) either adipose tissue. Overexpression transgenes tissue did affect fat content. Expression PNPLA3I148M, but PNPLA3WT,...
Phospholipase D (PLD) which was partially purified from membranes of porcine brain could be stimulated by multiple cytosolic components; these included ADP-ribosylation factor (Arf) and RhoA, required guanine nucleotides for activity, an unidentified activated the enzyme in a nucleotide-independent manner (Singer, W. D., Brown, H. A., Bokoch, G. M., Sternweis, P. C. (1995) J. Biol. Chem. 270, 14944-14950). Here, we report purification latter factor, its identification as alpha isoform...
Lipids orchestrate biological processes by acting remotely as signaling molecules or locally membrane components that modulate protein function. Detailed insight into lipid function requires knowledge of the subcellular localization individual lipids. We report an analysis lipidome mammalian macrophage, a cell type plays key roles in inflammation, immune responses, and phagocytosis. Nuclei, mitochondria, endoplasmic reticulum (ER), plasmalemma, cytoplasm were isolated from RAW 264.7...
ADP ribosylation factor (ARF) is a small guanosine triphosphate (GTP)-binding protein that regulates the binding of coat proteins to membranes and required for several stages vesicular transport. ARF also stimulates phospholipase D (PLD) activity, which can alter lipid content by conversion phospholipids into phosphatidic acid. Abundant PLD activity was found in Golgi-enriched from cell lines. Golgi greatly stimulated GTP analogs this stimulation could be inhibited brefeldin A (BFA), drug...
The mammalian target of rapamycin (mTOR) assembles a signaling network essential for the regulation cell growth, which has emerged as major anticancer therapies. tuberous sclerosis complex 1 and 2 (TSC1/2) proteins their target, small GTPase Rheb, constitute key regulatory pathway upstream mTOR. Phospholipase D (PLD) its product phosphatidic acid are also regulators mitogenic mTOR signaling. However, how TSC/Rheb PLD pathways interact or integrate in rapamycin-sensitive not been examined...
Molecular events involved in successful embryo implantation are not well understood. In this study, we used MALDI imaging mass spectrometry (IMS) technologies to characterize the spatial and temporal distribution of phospholipid species associated with mouse implantation. images showing within sites changed markedly between distinct cellular areas during days 4–8 pregnancy. For example, by day 8, linoleate- docosahexaenoate-containing phospholipids localized regions destined undergo cell...
Background and Aims The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, steatohepatitis (NASH), progression to cirrhosis. While differences in lipids between states have been reported, precise composition phospholipids diacylglycerols (DAG) at a lipid species level has not previously described. goal this study was characterize changes through human NAFLD using advanced lipidomic technology compare with murine model early NAFLD. Methods Utilizing mass spectrometry...
High levels of saturated FAs (SFAs) are acutely toxic to a variety cell types, including hepatocytes, and have been associated with diseases such as type 2 diabetes nonalcoholic fatty liver disease. SFA accumulation has previously shown degrade endoplasmic reticulum (ER) function leading other manifestations the lipoapoptotic cascade. We hypothesized that dysfunctional phospholipid (PL) metabolism is an initiating factor in this ER stress response. Treatment either primary hepatocytes or...
While differences in the rate of virus fusion and budding from host cell membrane have been correlated with pathogenicity, no systematic study contribution viral envelope composition has previously attempted. Using rigorous purification, marked between virions were observed. Over 125 phospholipid species quantitated for three strains influenza (HKx31- H3N2, PR8- H1N1, VN1203- H5N1) grown eggs. The glycerophospholipid purified differs that or typical mammalian cells. Phosphatidylcholine is...