A5047515959- Sphingolipid Metabolism and Signaling
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Protease and Inhibitor Mechanisms
- Inflammasome and immune disorders
- Cancer Mechanisms and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Enzyme function and inhibition
- RNA Research and Splicing
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Wound Healing and Treatments
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Oral microbiology and periodontitis research
- Enzyme Production and Characterization
- Studies on Chitinases and Chitosanases
- IL-33, ST2, and ILC Pathways
- ATP Synthase and ATPases Research
Virginia Commonwealth University
2012-2023
Virginia Commonwealth University Medical Center
2005-2008
VCU Massey Comprehensive Cancer Center
2008
University Health System
2007-2008
Cleveland State University
2001-2005
Jagiellonian University
1992-2002
University of Georgia
1995-1996
Westfälische Hochschule
1995
RWTH Aachen University
1992
Epigenetic Signals The lipid sphingosine-1-phosphate (S1P) is a signaling molecule that binds to receptors on the cell surface initiate biochemical changes control range of biological processes from growth and survival immune reactions. Hait et al. (p. 1254 ) report S1P can also function by direct binding nuclear enzymes, histone deacetylases (HDACs) 1 2. enzyme generates S1P, sphingosine kinase 2 (ShpK2) present in nucleus complexes with HDAC1 HDAC2. Generation its HDACs inhibited...
The potent lipid mediator sphingosine-1-phosphate (S1P) regulates diverse physiological processes by binding to 5 specific GPCRs, although it also has intracellular targets. Here, we demonstrate that S1P, produced in the mitochondria mainly sphingosine kinase 2 (SphK2), binds with high affinity and specificity prohibitin (PHB2), a highly conserved protein mitochondrial assembly function. In contrast, S1P did not bind closely related PHB1, which forms large, multimeric complexes PHB2. from...
Abstract Sphingosine-1-phosphate is a potent sphingolipid mediator of diverse processes important for brain tumors, including cell growth, survival, migration, invasion, and angiogenesis. Sphingosine kinase 1 (SphK1), one the two isoenzymes that produce sphingosine-1-phosphate, up-regulated in glioblastoma has been linked to poor prognosis patients with multiforme (GBM). In present study, we found isotype-specific SphK1 inhibitor, SK1-I, suppressed growth LN229 U373 lines nonestablished...
Sphingosine 1-phosphate (S1P), a potent lipid mediator, is ligand for family of five G protein-coupled receptors (S1P(1-5)) that have been shown to regulate variety biological responses important cancer progression. The cellular level S1P low and tightly regulated in spatio-temporal manner through its synthesis catalyzed by two sphingosine kinases, denoted SphK1 SphK2. Many stimuli activate translocate the plasma membrane mechanisms are dependent on phosphorylation. Much less known about...
Abstract Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 SphK2. Expression elevated in many cancers. Here, we report that LPA markedly enhanced mRNA protein gastric MKN1 cells but had no effect on also up-regulated expression other human endogenously express the LPA1 receptor, such as DLD1 colon MDA-MB-231 breast cells, not HT29 or...
The interleukin-13 receptor alpha2 (IL-13Rα2) is a cancer-associated overexpressed in human glioblastoma multiforme (GBM). This undetectable normal brain which makes it highly suitable target for diagnostic and therapeutic purposes. However, the pathological role of this GBM remains to be established. Here we report that IL-13Rα2 alone induces invasiveness cells without affecting their proliferation. In contrast, presence mutant EGFR (EGFRvIII), promotes cell proliferation vitro vivo....
α<sub>1</sub>-Antichymotrypsin (ACT) is an acute phase protein expressed in the brain which specifically colocalizes with amyloid-β during Alzheimer's disease. We analyzed ACT synthesis cultured human cortical astrocytes response to various cytokines and growth factors. Oncostatin M (OSM) interleukin (IL)-1β were potent stimulators of mRNA expression, whereas tumor necrosis factor-α had modest activity, IL-6 leukemia inhibitory factor (LIF) ineffective. The finding that OSM, but not LIF or...
The rat tissue inhibitor of metalloproteinases 1 (TIMP-1) gene is expressed in hepatocytes, and this expression Is up-regulated by interieukln 6 (IL-6). We report here the cloning 5′ flanking region TIMP-1 identification an IL-6/oncostatln M (OSM) response element at −64 to −36 which functions In hepatic cells. Within we have identified two functional binding sites for transcription factors AP-1 (activatory proteln-1) STAT (signal transducer activator transcription). IL-6/OSM stimulation...
Patients with gliomas expressing high levels of epidermal growth factor receptor (EGFR) and plasminogen activator inhibitor-1 (PAI-1) have a shorter overall survival prognosis. Moreover, EGF enhances PAI-1 expression in glioma cells. Although multiple known signaling cascades are activated by cells, we show for the first time that via sequential activation c-Src, protein kinase C delta (PKCdelta), sphingosine 1 (SphK1), enzyme produces sphingosine-1-phosphate. induced rapid phosphorylation...
The secreted protein, YKL-40, has been proposed as a biomarker of variety human diseases characterized by ongoing inflammation, including chronic neurologic pathologies such multiple sclerosis and Alzheimer's disease. However, inflammatory mediators the molecular mechanism responsible for enhanced expression YKL-40 remained elusive. Using several mouse models we now show that correlated with increased both IL-1 IL-6. Furthermore, together IL-6 or family cytokine, oncostatin M,...
The bioactive sphingolipid sphingosine-1-phosphate (S1P) and the kinase that produces it have been implicated in inflammatory bowel diseases mice humans; however, little is known about role of 2 S1P-specific phosphohydrolase isoforms, SGPP1 SGPP2, which catalyze dephosphorylation S1P to sphingosine. To elucidate their functions, we generated specific knockout mice. Deletion Sgpp2, mainly expressed gastrointestinal tract, significantly reduced dextran sodium sulfate (DSS)-induced colitis...
The bioactive sphingolipid metabolite, ceramide, regulates physiological processes important for inflammation and elevated levels of ceramide have been implicated in IL-1-mediated events. Although much has learned about generation by activation sphingomyelinases response to IL-1, the contribution de novo pathway is not completely understood. Because yeast ORM1 ORM2 proteins negatively regulate through inhibition serine palmitoyltransferase, first committed step biosynthesis, we examined...
Abstract Glioblastoma multiforme (GBM) is a primary brain tumor characterized by extensive necrosis and immunosuppressive inflammation. The mechanisms which this inflammation develops persists in GBM remain elusive. We identified two cytokines interleukin-1β (IL-1) oncostatin M (OSM) that strongly negatively correlate with patient survival. found these activate RelB/p50 complexes canonical NF-κB pathway, surprisingly drives expression of proinflammatory cells, but leads to their inhibition...