A5026232327- Lipid metabolism and biosynthesis
- Cannabis and Cannabinoid Research
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Ferroptosis and cancer prognosis
- Protein Degradation and Inhibitors
- Cancer, Lipids, and Metabolism
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Epigenetics and DNA Methylation
- Advanced Proteomics Techniques and Applications
- Metabolism, Diabetes, and Cancer
- Post-Soviet Geopolitical Dynamics
- ATP Synthase and ATPases Research
- Phagocytosis and Immune Regulation
- Sphingolipid Metabolism and Signaling
- Computational Drug Discovery Methods
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Amino Acid Enzymes and Metabolism
- interferon and immune responses
Scripps Research Institute
2022-2025
Scripps (United States)
2025
Scripps Institution of Oceanography
2025
Torrey Pines Institute For Molecular Studies
2025
The University of Texas at Austin
2024
University of Virginia
2018-2023
McCormick (United States)
2020
Northeast Catholic College
1957
Mutations in lipid regulator genes are a frequent cause of autism spectrum disorder, including those regulating phosphatidylinositol (PI) and phosphoinositide 3-kinase signaling. MBOAT7 encodes key acyltransferase PI synthesis is mutated an autism-related condition with neurodevelopmental delay epilepsy. Using liquid chromatography–tandem mass spectrometry, we analyzed the PI-associated glycerolipidome mice humans during neurodevelopment found dynamic regulation at times corresponding to...
ABSTRACT Activity-based protein profiling (ABPP) of stereoisomerically defined sets electrophilic compounds (‘stereoprobes’) offers a versatile way to discover covalent ligands for proteins in native biological systems. Here we report the synthesis and chemical proteomic characterization stereoprobes bearing P(V)-oxathiaphospholane (OTP) reactive group. ABPP experiments identified numerous human cancer cells that showed stereoselective reactivity with OTP stereoprobes, confirmed several...
Normal and oncogenic Ras proteins are functionally dependent on one or more lipid modifications 1,2 . Whereas K-Ras4b farnesylation is sufficient for stable association with the plasma membrane, farnesylated H-Ras, K-Ras4a, N-Ras traffic to Golgi where they must undergo palmitoylation before regulated translocation cell membranes. by DHHC family of palmitoyl acyl transferases (PATs) depalmitoylation ABHD17 serine hydrolases a dynamic process that essential growth acute myeloid leukemias...
Activity-based protein profiling (ABPP) of stereoisomerically defined sets electrophilic compounds ('stereoprobes') offers a versatile way to discover covalent ligands for proteins in native biological systems. Here we report the synthesis and chemical proteomic characterization stereoprobes bearing P(V)-oxathiaphospholane (OTP) reactive group. ABPP experiments identified numerous human cancer cells that showed stereoselective reactivity with OTP stereoprobes, confirmed several these...
Lipid droplets (LDs) are dynamic organelles that undergo changes in response to changing cellular conditions. During nutrient depletion, LD numbers increase protect cells against toxic fatty acids generated through autophagy and provide fuel for beta-oxidation. However, the precise mechanisms which these regulated have remained unclear. Here, we show small GTPase RalA acts downstream of directly facilitate growth during depletion. Mechanistically, performs this function phospholipase D1...
Background: Patients with rheumatoid arthritis (RA) experience joint swelling and cartilage destruction resulting in chronic pain, functional disability, compromised function. Current RA treatments, including glucocorticoid receptor agonists, produce adverse side effects lack prolonged treatment efficacy. Cannabinoids (i.e., cannabis-like signaling molecules) exert anti-inflammatory analgesic limited compared to traditional immunosuppressants, making them excellent targets for the...
Diacylglycerol lipase-beta (DAGLβ) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages dendritic cells. Genetic or pharmacological inactivation of DAGLβ ameliorates inflammation hyper-nociception preclinical models pathogenic pain. These beneficial effects have been assigned principally to reductions downstream proinflammatory lipid signaling, leaving alternative mechanisms...
Abstract Ferroptosis is an iron-dependent form of cell death driven by the oxidation polyunsaturated (PUFA) phospholipids. Large-scale genetic screens have pointed to a specialized role for PUFA ether phospholipids (ePLs) in promoting ferroptosis. Our understanding enzymes involved ePL production, however, remains incomplete. Here we show using combination pathway mining dependency maps, AlphaFold-guided structure predictions, and targeted lipidomics that uncharacterized transmembrane...
Diacylglycerol lipase-beta (DAGLB) functions as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme most well known for its role in endocannabinoid and eicosanoid metabolism immune cells including macrophages dendritic cells. Genetic or pharmacological disruption of DAGLB ameliorates inflammation hyper-nociception behavioral models pain. These beneficial effects have been ascribed principally to reductions downstream pro-inflammatory lipid signaling; whether alternative mechanisms...
Here, we apply chemical proteomics and untargeted lipidomics to assign a novel polyunsaturated fatty acid (PUFA)-specific triacylglycerol (TAG) lipase activity for diacylglycerol lipase-beta (DAGLβ) in macrophages. We demonstrate that DAGLβ but not DAGLα is expressed active bone marrow-derived macrophages (BMDMs) as determined by DAGL-directed activity-based protein profiling (ABPP). Genetic disruption of resulted accumulation cellular TAGs composed PUFA saturated/low unsaturated FA...
Abstract Lipid phosphorylation is an understudied regulatory mechanism for T cell metabolism and signaling. Specifically, diacylglycerol kinases (DGKs) modulate intracellular levels of the secondary messengers phosphatidic acid, which are implicated in regulation activation anergy. Development isoform-selective DGK inhibitors challenging but needed to understand specificity biology vivo. Towards this goal, we use ATP acyl phosphate activity-based probes quantitative mass spectrometry define,...
Lipid droplets (LDs) are dynamic organelles that undergo changes in size, abundance and intracellular distribution response to changing cellular conditions. During nutrient depletion, LD numbers increase protect cells against toxic fatty acids generated through autophagy provide fuel for beta-oxidation. However, the precise mechanisms which these regulated have remained unclear. Here, we show small GTPase RalA is required growth under conditions of amino acid depletion. Further, find acts...