A5001957935- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Lipid metabolism and biosynthesis
- Biomedical Research and Pathophysiology
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Genomics, phytochemicals, and oxidative stress
- SARS-CoV-2 and COVID-19 Research
- Genetic factors in colorectal cancer
- Neonatal Health and Biochemistry
- Epigenetics and DNA Methylation
- SARS-CoV-2 detection and testing
- Literature: history, themes, analysis
- Chemotherapy-induced organ toxicity mitigation
- Metabolism, Diabetes, and Cancer
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- COVID-19 Clinical Research Studies
- Pharmacogenetics and Drug Metabolism
- Diet, Metabolism, and Disease
Virginia Commonwealth University
2017-2025
Washington University in St. Louis
2024
University of Louisville
2022
Children's Hospital of Richmond at VCU
2021
Sphingolipids compose a lipid family critical for membrane structure as well intra- and intercellular signaling. De novo sphingolipid biosynthesis is initiated by the enzyme serine palmitoyltransferase (SPT), which resides in endoplasmic reticulum (ER) membrane. In both yeast mammalian species, SPT activity homeostatically regulated through small ER proteins, Orms ORMDLs cells. These proteins form stable complexes with SPT. yeast, homeostatic regulation of relies, at least part, on...
The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that replicates less efficiently lung tissue compared to ancestral strain. However, infectivity gastrointestinal tract is not fully defined, despite fact 70% COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless individual variability, infects colon...
Sphingolipids play crucial roles in cell membrane structure and multiple signaling pathways. Sphingolipid de novo biosynthesis is mediated by the serine palmitoyltransferase (SPT) enzyme complex. Homeostatic regulation of this complex dependent on its regulatory subunit, ORMDLs, which there are three isoforms. It well established that ORMDLs regulate SPT activity, but it still unclear whether ORMDL isoforms have distinct functions properties. Here, we focus understanding physiological...
Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content synthesis have not been well characterized in oligodendrocytes, the myelin-producing cells of CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, biochemical assays, we examined during peak period myelination postnatal rat brain. Importantly, production isolated oligodendrocytes. We...
The serine palmitoyltransferase (SPT) complex catalyzes the rate-limiting step in de novo biosynthesis of ceramides, precursors sphingolipids. mammalian ORMDL isoforms (ORMDL1-3) are negative regulators SPT. However, roles individual unclear. Using siRNA against ORMDLs, only single siORMDL3 had modest effects on dihydroceramide and ceramide levels, whereas downregulation all three ORMDLs induced more pronounced increases. With CRISPR/Cas9-based genome-editing strategy, we established stable...
Cisplatin is a commonly used chemotherapeutic for the treatment of many solid organ cancers; however, its effectiveness limited by development acute kidney injury (AKI) in 30% patients. AKI driven proximal tubule cell death, leading to rapid decline renal function. It has previously been shown that sphingolipid metabolism plays role regulating biological processes involved cisplatin-induced AKI. For example, neutral ceramidase (nCDase) an enzyme responsible converting ceramide into...
Abstract Myelin is a unique, lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical components of myelin. Here we examined sphingolipid synthesis during the peak period myelination in postnatal rat brain. Importantly, made measurements isolated oligodendrocytes, myelin-producing cells central nervous system. We analyzed distribution levels enzymes regulators biosynthetic pathway, with focus on serine palmitoyltransferase...
Sphingolipids, the large class of lipids based on sphingosine backbone, have diverse functions in health and disease. The overall rate synthesis sphingolipid pool is determined by serine palmitoyltransferase (SPT), initiating enzyme de novo biosynthetic pathway. SPT subject to homeostatic regulation such that elevated cellular results decreased activity. This mediated small proteins endoplasmic reticulum: Orms yeast ORMDLs mammalian cells. are negative regulators SPT. Here we describe...
Serine palmitoyltranferase (SPT) is a pyridoxal 5' phosphate (PLP)-dependent enzyme that catalyzes the first and rate-limiting step of de novo synthesis sphingolipids. SPT activity homeostatically regulated in response to increased levels This homeostatic regulation mediated through small ER membrane proteins termed ORMDLs. Here we describe procedure assay ORMDL dependent lipid inhibition activity. The using radiolabeled L-serine was developed from established by Hornemann laboratory. can...
Abstract INTRODUCTION Dysregulated barrier function contributes to the pathogenesis in inflammatory bowel diseases (Crohn’s (CD) and ulcerative colitis (UC)). The cytosolic transcription factor aryl hydrocarbon receptor (AHR) is activated by both endogenous exogenous ligands, functionally maintaining mucosal homeostasis. Recently, we demonstrated that AHR activity promotes a pro-restitutive program small intestine, but this pathway disrupted Crohn’s disease. In study, sought identify genetic...