A5011733159- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Lipid Membrane Structure and Behavior
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Hedgehog Signaling Pathway Studies
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Drug Transport and Resistance Mechanisms
- Lipid metabolism and biosynthesis
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Cancer, Lipids, and Metabolism
- Microtubule and mitosis dynamics
- Telomeres, Telomerase, and Senescence
- Phagocytosis and Immune Regulation
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Biochemical and Molecular Research
- Nanoplatforms for cancer theranostics
- Cell death mechanisms and regulation
Medical University of South Carolina
2016-2025
MUSC Hollings Cancer Center
2016-2025
College of Charleston
2003-2013
Louisiana Cancer Research Center
2013
Tulane University
2013
Louisiana State University
2013
Louisiana State University Health Sciences Center New Orleans
2013
University of Charleston
2005-2013
Johns Hopkins University
2013
Shanghai East Hospital
2013
Abstract Mechanisms that alter protein phosphatase 2A (PP2A)‐dependent lung tumour suppression via the I2PP2A/SET oncoprotein are unknown. We show here suppressor ceramide binds selectively in nucleus and including its K209 Y122 residues as determined by molecular modelling/simulations site‐directed mutagenesis. Because was found overexpressed, whereas downregulated tumours, a sphingolipid analogue drug, FTY720, identified to mimick for binding targeting I2PP2A/SET, leading PP2A...
The success of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) depends on the requirement for BCR-ABL1 activity CML progenitors. However, quiescent HSCs are TKI resistant and represent a kinase-independent disease reservoir. Here we have shown that persistence leukemic BM requires inhibition tumor suppressor protein phosphatase 2A (PP2A) expression--but not activity--of oncogene. Examination from patients healthy individuals revealed PP2A was suppressed compared...
Previous studies have demonstrated that several splice variants are derived from both the caspase 9 and Bcl-x genes in which variant, Bcl-x(L) 9b, inhibit apoptosis contrast to pro-apoptotic variants, Bcl-x(s) 9. In a recent study, we showed ceramide induces dephosphorylation of SR proteins, family protein factors regulate alternative splicing. this regulation processing pre-mRNA was examined response ceramide. Treatment A549 lung adenocarcinoma cells with cell-permeable ceramide, D-e-C6...
Emerging results suggest that ceramides with different fatty acid chain lengths might play distinct functions in the regulation of tumor growth and therapy. Here we report de novo-generated C(18)- C(16)-ceramides by ceramide synthases 1 6 (CerS1 CerS6) opposing proapoptotic prosurvival roles, respectively, human head neck squamous cell carcinomas (HNSCCs). Unexpectedly, knockdown CerS6/C(16)-ceramide using small interfering RNA induced endoplasmic reticulum (ER)-stress-mediated apoptosis....
In this study, endogenous long chain ceramides were measured in 32 human head and neck squamous cell carcinoma (HNSCC) 10 nonsquamous tumor tissues, as compared with adjacent noncancerous by liquid chromatography/mass spectroscopy. Interestingly, only one specific ceramide, C18:0-ceramide, was selectively down-regulated the majority of HNSCC tissues. On other hand, selectivity for C18-ceramide not detected. These data suggested hypotheses that decreased levels C -ceramide might impart a...
In this study, mechanisms of resistance to imatinib-induced apoptosis in human K562 cells were examined. Continuous exposure stepwise increasing concentrations imatinib resulted the selection K562/IMA-0.2 and -1 cells, which expressed ∼2.3- 19-fold resistance, respectively. Measurement endogenous ceramides by high performance liquid chromatography/mass spectroscopy showed that treatment with increased generation ceramide, mainly C18-ceramide, is generated longevity assurance gene 1 (hLASS1),...
In this study, the inhibitor 2 of protein phosphatase 2A (I2PP2A) was identified in vitro and situ as a ceramide-binding protein, which exhibits stereoisomer specificity fatty acid chain length preference. Site- directed mutagenesis coupled with structural details I2PP2A suggested that VIK 207-209 residues localized on helix 7 are important for ceramide binding single mutation K209D altered interaction. Notably, I2PP2A-ceramide decreased association between PP2A inhibitor, preventing...
Treatment of A549 cells with C6-ceramide resulted in a significant increase the endogenous long chain ceramide levels, which was inhibited by fumonisin B1 (FB1), and not myriocin (MYR). The biochemical mechanisms generation were investigated using treated selectively labeled C6-ceramides, [sphingosine-3-3H]d-erythro-, N-[N-hexanoyl-1-14C]d-erythro-C6-ceramide. results demonstrated that 3H label incorporated into newly synthesized ceramides, FB1 MYR. Interestingly, 14C ceramides. Taken...
Sphingosine kinase 1 (SK1) is a key enzyme critical to the sphingolipid metabolic pathway responsible for catalyzing formation of bioactive lipid sphingosine-1-phosphate. SK1-mediated production sphingosine-1-phosphate has been shown stimulate such biological processes as cell growth, differentiation, migration, angiogenesis, and inhibition apoptosis. In this study, type–specific immunolocalization SK1 was examined in bronchus/terminal bronchiole lung. Strong immunopositive staining evident...
The role of dihydroceramide desaturase as a key enzyme in the de novo pathway ceramide generation was investigated human neuroblastoma cells (SMS-KCNR). A novel assay using water-soluble analogs dihydroceramide, dihydroceramidoids (d-erythro-dhCCPS analogs), used to measure activity situ. Conversion d-erythro-2-N-[12′-(1″-pyridinium)-dodecanoyl]-4,5-dihydrosphingosine bromide (C12-dhCCPS) its 4,5-desaturated counterpart, d-erythro-2-N-[12′-(1″-pyridinium)dodecanoyl]sphingosine (C12-CCPS),...
Abstract In this study, quantitative isobologram studies showed that treatment with gemcitabine and doxorubicin, known inducers of ceramide generation, in combination, supra-additively inhibited the growth human UM-SCC-22A cells situ. Then, possible involvement homologue yeast longevity assurance gene 1 (LASS1)/C18-ceramide chemotherapy-induced cell death these was examined. Gemcitabine/doxorubicin combination resulted elevation mRNA protein levels LASS1 not LASS2-6, which consistent a...
Purpose: Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic proinflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated safety, pharmacokinetics, pharmacodynamics, antitumor activity of ABC294640, a first-in-class orally available inhibitor SK2.Experimental Design: Escalating doses ABC294640 were administered to patients with advanced solid tumors in sequential cohorts at following dose levels: 250 mg qd, bid, 500 750 continuously...
Sphingosine 1-phosphate binds and stabilizes telomerase, a process that could be targeted to promote senescence reduce cancer growth.