A5056710085- Sphingolipid Metabolism and Signaling
- Immune Cell Function and Interaction
- Lipid Membrane Structure and Behavior
- Retinal Development and Disorders
- Endoplasmic Reticulum Stress and Disease
- PARP inhibition in cancer therapy
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Heat shock proteins research
- Cellular transport and secretion
- Retinal Diseases and Treatments
- Immune cells in cancer
- Photoreceptor and optogenetics research
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Inflammatory Biomarkers in Disease Prognosis
- Carbohydrate Chemistry and Synthesis
- TGF-β signaling in diseases
- Platelet Disorders and Treatments
- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Pancreatic and Hepatic Oncology Research
- Cancer survivorship and care
- Colorectal and Anal Carcinomas
- Calcium signaling and nucleotide metabolism
Skidmore College
2023-2024
Bengbu Medical College
2023
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2020-2022
The Ohio State University
2019-2022
University of Oxford
2020
Medical University of South Carolina
2010-2019
MUSC Hollings Cancer Center
2013-2019
University of South Carolina
2017
University of Charleston
2015
College of Charleston
2014
RPE65 is an abundant protein in the retinal pigment epithelium. Mutations are associated with inherited dystrophies. Although it known that critical for regeneration of 11- cis retinol visual cycle, function elusive. Here we show recombinant RPE65, when expressed QBI-293A and COS-1 cells, has robust enzymatic activity previous unidentified isomerohydrolase, enzyme converting all-trans retinyl ester to cycle. The initial rate reaction 2.9 pmol/min per mg 293A cells. isomerohydrolase requires...
Cancer-associated thrombocytosis has long been linked to poor clinical outcome, but the underlying mechanism is enigmatic. We hypothesized that platelets promote malignancy and resistance therapy by dampening host immunity. show genetic targeting of enhances adoptive T cell cancer. An unbiased biochemical structural biology approach established transforming growth factor β (TGFβ) lactate as major platelet-derived soluble factors obliterate CD4+ CD8+ functions. Moreover, we found are dominant...
Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and relapse. The influence sphingolipids, such as ceramide its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation...
Increasing evidence points to a role for the protein quality control in endoplasmic reticulum (ER) maintaining intestinal homeostasis. However, specific general ER chaperones this process remains unknown. Herein, we report that major heat shock grp94 interacts with MesD, critical chaperone Wnt coreceptor low-density lipoprotein receptor-related 6 (LRP6). Without grp94, LRP6 fails export from cell surface, resulting profound loss of canonical signaling. The significance finding is...
Proteolysis of platelet-bound GARP by thrombin liberates active TGF-β and contributes to cancer immune evasion in the tumor microenvironment.
Significance Ceramide is a bioactive lipid involved in numerous cellular functions and disease states that are critically dependent on its site of generation. nSMase2 generates ceramide at the inner leaflet plasma membrane therapeutic target for cancer neurological disorders. Although much known about nSMase2, there limited insight into molecular mechanisms regulating activity. Here we present crystal structure identify lipid-binding N-terminal domain as an allosteric activation domain. Key...
GARP encoded by the Lrrc32 gene is cell surface docking receptor for latent TGFβ, which expressed naturally platelets and regulatory T cells (Treg). Although amplified frequently in breast cancer, expression relevant functions of cancer have not been explored. Here, we report that exerts oncogenic effects, promoting immune tolerance enriching activating TGFβ tumor microenvironment. We found human breast, lung, colon cancers aberrantly. In genetic studies normal mammary gland epithelial...
Sphingolipids play important roles in regulating cellular responses. Although mitochondria contain sphingolipids, direct regulation of their levels or mitochondria-associated membranes is mostly unclear. Neutral SMase (N-SMase) isoforms, which catalyze hydrolysis sphingomyelin (SM) to ceramide and phosphocholine, have been found the yeast zebrafish, yet existence mammalian remains unknown. Here, we identified cloned a cDNA based on nSMase homologous sequences. This encodes novel protein 483...
Reports suggest that excessive ceramide accumulation in mitochondria is required to initiate the intrinsic apoptotic pathway and subsequent cell death, but how accumulates unclear. Here we report liver exhibit formation from sphingosine palmitoyl-CoA palmitate. Importantly, this activity was markedly decreased neutral ceramidase (NCDase)-deficient mice. Moreover, levels of were dissimilar WT NCDase KO These results a key participant mitochondria. We also highly purified have ceramidase,...
Molecular chaperones control a multitude of cellular functions via folding chaperone-specific client proteins. CD4+FOXP3+ Tregs play key roles in maintaining peripheral tolerance, which is subject to regulation by multiple molecular switches, including mTOR and hypoxia-inducible factor. It not clear whether GP96 (also known as GRP94), master TLR integrin chaperone, controls Treg function. Using murine genetic models, we demonstrated that required for maintenance function, loss resulted...
Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of metabolism may emerge as novel regulators targets cancer. Neutral ceramidase (nCDase), a key enzyme hydrolyzes into sphingosine, is highly expressed the intestine; however, its role cancer has not defined. Here we show molecular pharmacological inhibition nCDase cells increases ceramide, this accompanied by decreased cell survival increased...
Abstract Activated regulatory T (Treg) cells express the surface receptor glycoprotein-A repetitions predominant (GARP), which binds and activates latent TGFβ. How GARP modulates Treg function in inflammation cancer remains unclear. Here we demonstrate that loss of leads to spontaneous with highly activated CD4+ CD8+ development enteritis. lacking were unable suppress pathogenic T-cell responses multiple models inflammation, including transfer colitis. GARP−/− significantly reduced gut...
Multiple studies have addressed the mechanisms by which ultraviolet (UV) light induces cell death, and a few focused on stress mediators such as acid sphingomyelinase (ASMase) or protein kinase Cdelta (PKCdelta). Based recent study that identified novel mechanism of activation ASMase through phosphorylation, current was undertaken to determine upstream regulating in response UV investigate role its phosphorylation at S508 an integral event during light-induced death. Exposure MCF-7 breast...