A5018277782- Sphingolipid Metabolism and Signaling
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Lipid Membrane Structure and Behavior
- Peroxisome Proliferator-Activated Receptors
- Bacterial Genetics and Biotechnology
- Cellular transport and secretion
- 3D Printing in Biomedical Research
- Fungal and yeast genetics research
- Protein Structure and Dynamics
- Erythrocyte Function and Pathophysiology
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Metabolism and Genetic Disorders
- Lipid metabolism and disorders
- Pancreatic function and diabetes
- Drug Transport and Resistance Mechanisms
- Bioinformatics and Genomic Networks
- Genetics, Aging, and Longevity in Model Organisms
- Pancreatitis Pathology and Treatment
- Advanced biosensing and bioanalysis techniques
- Ion Transport and Channel Regulation
- Liver physiology and pathology
- Protein Kinase Regulation and GTPase Signaling
Virginia Commonwealth University
2018-2025
Régie Autonome des Transports Parisiens (France)
2019
University of Nebraska–Lincoln
2015-2016
Medical University of South Carolina
2009-2013
University of Massachusetts Amherst
2003-2008
FATP2 as the gatekeeper (A), dysregulation of fatty acid metabolism from FA overload (B), and Lipofermata or Grassofermata treatment (C).
Nonalcoholic fatty liver disease (NAFLD), a leading cause of dysfunction, is metabolic that begins with steatosis. Sphingolipid metabolites, particularly ceramide and sphingosine-1-phosphate (S1P), have recently received attention for their potential roles in insulin resistance hepatic FTY720/fingolimod, prodrug the treatment multiple sclerosis, phosphorylated vivo to its active form by sphingosine kinase 2 has been shown interfere actions S1P inhibit biosynthesis. Therefore, this study we...
Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, cellular roles are not completely understood. Sphingolipids produced by serine palmitoyltransferase enzyme, canonically composed 2 subunits, SPTLC1 (serine long chain base subunit 1) SPTLC2 2). Noncanonical sphingolipids a more recently described subunit, SPTLC3 3).
Transmembrane receptors in the signaling pathways of bacterial chemotaxis systems influence cell motility by forming noncovalent complexes with cytoplasmic proteins to regulate their activity. The requirements for receptor-mediated activation CheA, principal kinase Escherichia coli pathway, were investigated using self-assembled clusters a receptor fragment (CF) derived from domain aspartate receptor, Tar. Histidine-tagged Tar CF was assembled on surface sonicated unilamellar vesicles via...
Distinct transcriptional modules are regulated by specific ceramides.
Sphingolipids such as ceramide are recognized vital regulators of many biological processes. Neutral sphingomyelinase 2 (nSMase2) is one the key enzymes regulating production. It was previously shown that enzymatic activity nSMase2 dependent on anionic phospholipids (APLs). In this study, structural requirements for APL-selective binding were determined and characterized. Using lipid-protein overlay assays, interacted specifically directly with several APLs, including phosphatidylserine...
In non-alcoholic steatohepatitis (NASH), many lines of investigation have reported a dysregulation in lipid homeostasis, leading to intrahepatic accumulation. Recently, the role dysfunctional sphingolipid metabolism has also been proposed. Human and animal models NASH associated with elevated levels long chain ceramides pro-apoptotic metabolites, implicated regulating fatty acid oxidation inflammation. Importantly, inhibition de novo ceramide biosynthesis or knock-down synthases reverse some...
Sphingolipids have become established participants in the pathogenesis of obesity and its associated maladies. Sphingosine kinase 1 (SPHK1), which generates S1P, has been shown to increase liver adipose obese humans mice regulate inflammation hepatocytes tissue, insulin resistance, systemic mouse models obesity. Previous studies by us others demonstrated that global sphingosine KO are protected from diet-induced obesity, inflammation, NAFLD, suggesting SPHK1 may mediate pathological outcomes...
All cells possess transmembrane signaling systems that function in the environment of lipid bilayer. In Escherichia coli chemotaxis pathway, binding attractants to a two-dimensional array receptors and proteins simultaneously inhibits an associated kinase stimulates receptor methylation--a slower process restores activity. These two opposing effects lead robust adaptation toward stimuli through physical mechanism is not understood. Here, we provide evidence counterbalancing influence exerted...
Saccharomyces cerevisiae cells lacking ISC1 (inositol phosphosphingolipase C) exhibit sensitivity to genotoxic agents such as methyl methanesulfonate and hydroxyurea (HU). Cell cycle analysis by flow cytometry revealed a G(2)/M block in isc1Delta when treated with or HU. Further investigation that the levels of Cdc28 phosphorylated on Tyr-19, which plays an essential role regulation checkpoint, were higher synchronized asynchronous response Use Cdc28-Y19F mutant protected from block. In wild...
Problems in membrane biology require methods to recreate the interactions between receptors and cytoplasmic signaling proteins at surface. Here, unilamellar vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine a nickel-chelating lipid were used as templates direct assembly from Escherichia coli chemotaxis pathway. The bacterial chemoreceptors are known form clusters, which promote binding adaptor protein (CheW) kinase (CheA). When CheA was incubated with vesicles, CheW,...
Serine palmitoyltransferase (SPT) catalyzes the first committed step of de novo sphingolipid biosynthesis. The canonical SPT catalytic core is composed two constitutively expressed subunits, SPTLC1 and SPTLC2. SPTLC3 an inducible subunit complex which can substitute for SPTLC2, leading to production alternative sphingoid bases including a 16-carbon dihydrosphingosine (d16-DHS). physiological significance remains largely unexplored. Here we report time that essential gluconeogenesis,...
Sphingosine kinase 1 (SphK1) plays a crucial role in regulating metabolic pathways within adipocytes and is elevated the adipose tissue of obese mice. While previous studies have reported both pro- inhibitory effects SphK1 its product, sphingosine-1-phosphate (S1P), on adipogenesis, precise mechanisms remain unclear. This study explores timing downstream SphK1/S1P expression activation during