A5012521971- Sphingolipid Metabolism and Signaling
- Microtubule and mitosis dynamics
- Erythrocyte Function and Pathophysiology
- Inflammasome and immune disorders
- Lipid Membrane Structure and Behavior
- Caveolin-1 and cellular processes
- Immune Response and Inflammation
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Fibroblast Growth Factor Research
- Sepsis Diagnosis and Treatment
- Liver Disease Diagnosis and Treatment
- Effects of Radiation Exposure
- Immune cells in cancer
- Circadian rhythm and melatonin
- Endoplasmic Reticulum Stress and Disease
- Lysosomal Storage Disorders Research
- Asthma and respiratory diseases
- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Ion Transport and Channel Regulation
- DNA Repair Mechanisms
- Inflammation biomarkers and pathways
- Cellular transport and secretion
- Spondyloarthritis Studies and Treatments
Virginia Commonwealth University
2020-2024
Jena University Hospital
2014-2024
Friedrich Schiller University Jena
2024
VCU Massey Comprehensive Cancer Center
2022
Virginia Cancer Institute
2022
Children's Hospital of Richmond at VCU
2021
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
2016-2020
Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to infection and is leading cause mortality on intensive care units (ICU) worldwide. An acute episode sepsis characterized by extensive release cytokines other mediators resulting in a dysregulated immune organ damage and/or death. This initial pro-inflammatory burst often transits into state suppression characterised loss cells T-cell dysfunction at later disease stages survivors. However, despite...
Abstract Non‐alcoholic steatohepatitis (NASH) results from the accumulation of excessive liver lipids leading to hepatocellular injury, inflammation, and fibrosis that greatly increase risk for carcinoma (HCC). Despite well‐characterized clinical histological pathology NASH‐driven HCC in humans, its etiology remains unclear there is a deficiency pre‐clinical models recapitulate progression human disease. Therefore, we developed new mouse model amenable genetic manipulations gene targeting...
Sepsis is a systemic inflammatory response to pathogens and leading cause of hospital related mortality worldwide. Sphingosine 1‐phosphate (S1P) regulates multiple cellular processes potentially involved in the pathogenesis sepsis, including antigen presentation, lymphocyte egress, maintenance vascular integrity. We thus explored impact manipulating S1P signaling experimental polymicrobial sepsis mice. Administration 4‐deoxypyridoxine (DOP), an inhibitor S1P‐degrading enzyme S1P‐lyase, or...
Genome-wide association studies have linked the ORM (yeast)-like protein isoform 3 (ORMDL3) to asthma severity. Although ORMDL3 is a member of family that negatively regulates serine palmitoyltransferase (SPT) and thus biosynthesis sphingolipids, it still unclear whether altered sphingolipid synthesis are causally related non-Th2 severe associated with predominant neutrophil inflammation high interleukin-17 (IL-17) levels. Here, we examined effects overexpression in preclinical mouse model...
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...
The palatine tonsils, localized in the oropharynx, are easily accessible secondary lymphoid tissue humans. Inflammation of local and chronic case tonsillitis (CT) or acute presence a peritonsillar abscess (PTA), ranks among most common diseases otolaryngology. However, functionality tonsillar immune cells, notably T-cells, context these pathologies is poorly understood. We have examined functional status human T-cells CT compared it to inflammatory setting PTA. Patients presenting with (n =...
One-third of all deaths in hospitals are caused by sepsis. Despite its demonstrated prevalence and high case fatality rate, antibiotics remain the only target-oriented treatment option currently available. Starting from results showing that low-dose anthracyclines protect against sepsis mice, we sought to find new causative options improve outcomes. Sepsis was induced different were evaluated regarding cytokine biomarker expression, lung epithelial cell permeability, autophagy induction,...
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder arising from mutations in the cholesterol-trafficking protein NPC1 (95%) or NPC2 (5%). These result accumulation of low-density lipoprotein-derived cholesterol late endosomes/lysosomes, disruption endocytic trafficking, and stalled autophagic flux. Additionally, NPC results sphingolipid accumulation, yet it unique among sphingolipidoses because absence enzymes responsible for degradation. In this work, we examined cause...
Abstract Reciprocal interactions between breast cancer cells and the tumor microenvironment (TME) are important for progression metastasis. We report here that deletion or inhibition of sphingosine kinase 2 (SphK2), which produces sphingosine-1-phosphate (S1P), markedly suppresses syngeneic growth lung metastasis in mice by creating a hostile invasion. SphK2 deficiency decreased S1P concomitantly increased ceramides, including C16-ceramide, stromal fibroblasts. Ceramide accumulation...
Abstract Paclitaxel is among the most active chemotherapy drugs for aggressive triple negative breast cancer (TNBC). Unfortunately, it often induces painful peripheral neuropathy (CIPN), a major debilitating side effect. Here we demonstrate that in naive and tumor‐bearing immunocompetent mice, clinically relevant dose of FTY720/Fingolimod targets sphingosine‐1‐phosphate receptor 1 (S1PR1), alleviated paclitaxel‐induced neuropathic pain. FTY720 also significantly attenuated...
The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one most effective EC barrier-stabilizing signaling molecules. Stabilization mainly transduced via S1P receptor type 1 (S1PR1). Here, we demonstrate that was autonomously produced by ECs. secretion higher in primary human umbilical vein cells (HUVEC) compared line EA.hy926. Constitutive stability HUVEC, but not EA.hy926, compromised S1PR1 antagonist W146 and...
Membrane contact sites (MCS), close membrane apposition between organelles, are platforms for interorganellar transfer of lipids including cholesterol, regulation lipid homeostasis, and co-ordination endocytic trafficking. Sphingosine kinases (SphKs), two isoenzymes that phosphorylate sphingosine to the bioactive sphingosine-1-phosphate (S1P), have been implicated in However, physiological functions SphKs dynamics, trafficking MCS not known. Here, we report deletion decreased S1P with...
The aim of this study was to examine T cell function in tonsils patients with recurrent acute tonsillitis (RAT) or peritonsillar abscess (PTA) by analyzing the cytokine production following receptor (TCR) and co-receptor stimulation a combination anti-CD3 anti-CD28 antibodies. release IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 IL-17A from isolated, stimulated cells 27 palatine (10 RAT, 7 PTA, 10 without inflammation) measured via bead-based flow cytometric analysis. results were compared isolated...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality, and its incidence increasing due to endemic obesity. HCC sexually dimorphic in both humans rodents with higher males, although mechanisms contributing these correlations remain unclear. Here, we examined role sphingosine kinase 2 (SphK2), enzyme that regulates balance bioactive sphingolipid metabolites, sphingosine-1-phosphate (S1P) ceramide, gender specific MASH-driven HCC. Male female mice were fed a high fat...
Invasion of brain endothelial cells (BECs) is central to the pathogenicity Neisseria meningitidis infection. Here, we established a key role for bioactive sphingolipid sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) 2 in uptake process. Quantitative sphingolipidome analyses BECs infected with N . revealed elevated levels, which could be attributed enhanced expression enzyme sphingosine kinase 1 its activity. Increased activity was dependent on interaction meningococcal type IV pilus...
Ventilator-induced Lung Injury (VILI) is characterized by hypoxia, inflammatory cytokine influx, loss of alveolar barrier integrity, and decreased lung compliance. Aging influences structure function a predictive factor in the severity VILI; however, mechanisms aging that influence progression or increased susceptibility remain unknown. impacts immune system may increase inflammation healthy individuals. Recent studies suggest bioactive sphingolipid mediator sphingosine-1-phosphate (S1P)...
The bioactive sphingolipid metabolites ceramide and sphingosine-1-phosphate (S1P) accumulate with overnutrition have been implicated in non-alcoholic steatohepatitis (NASH) development. ORMDL3, a negative regulator of the rate-limiting step biosynthesis, has identified as an obesity-related gene. Therefore, we assessed role ORMDL3 diet-induced obesity development NASH.
Sphingosine 1-phosphate (S1P) is a cellular and extracellular signaling molecule that acts locally in different organs also systemically present blood lymph. S1P well characterized immune modulator influencing lymphocyte circulation cell differentiation, survival, function, migration, locality. Many of these functions are relevant for the pathology tumor cells, there body evidence supporting fact fulfils similar cancer. This review aims to summarize current knowledge about roles growth...