Edwin C.K. Wan

Edwin C.K. Wan
West Virginia University | WVU · Department of Microbiology, Immunology and Cell Biology

Ph.D.

About

35
Publications
7,410
Reads
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1,252
Citations
Introduction
Identifying cytokines and underlying signaling pathways that govern the pathogenesis of neuroinflammation.
Additional affiliations
August 2016 - present
West Virginia University
Position
  • Faculty Member
August 2016 - present
West Virginia University
Position
  • Professor (Assistant)
November 2008 - July 2016
National Heart, Lung, and Blood Institute
Position
  • PostDoc Position
Education
September 2002 - February 2007
City University of Hong Kong
Field of study
  • Cancer Immunology and Pharmacology

Publications

Publications (35)
Article
Full-text available
Signal tranducer and activator of transcription 5 (STAT5) plays a critical role in mediating cellular responses following cytokine stimulation. STAT proteins critically signal via the formation of dimers, but additionally, STAT tetramers serve key biological roles, and we previously reported their importance in T and natural killer (NK) cell biolog...
Article
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Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known, but it is generally accepted that it is autoimmune in nature. Our knowledge of the pathogenesis of MS has increased tremendously in the past decade through clinical studies and the use of experimental autoimmune encephalomyelit...
Article
As mitigation of brain aging continues to be a key public health priority, a wholistic and comprehensive consideration of the aging body has identified immunosenescence as a potential contributor to age-related brain injury and disease. Importantly, the nervous and immune systems engage in bidirectional communication and can exert profound influenc...
Article
Immune cell expansion, activation, and trafficking to the lungs, which are controlled by the expression of multiple cytokines and chemokines, may be altered by severe brain injury. This is evidenced by the fact that pneumonia is a major cause of mortality in patients who have suffered from ischemic stroke. The goal of this protocol is to describe t...
Article
Full-text available
Multiple sclerosis (MS) is an immune-mediated disease that predominantly impacts the central nervous system (CNS). Animal models have been used to elucidate the underpinnings of MS pathology. One of the most well-studied models of MS is experimental autoimmune encephalomyelitis (EAE). This model was utilized to demonstrate that the cytokine granulo...
Article
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Mucosal‐associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19‐Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iVα19TCR and their regulation in MAIT cells are unknown. Diacylglycer...
Article
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CD4+ T helper (TH) cells are critical for protective adaptive immunity against pathogens, and they also contribute to the pathogenesis of autoimmune diseases. How TH differentiation is regulated by the TCR's downstream signaling is still poorly understood. We describe here that diacylglycerol kinases (DGKs), which are enzymes that convert diacylgly...
Article
Full-text available
Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6C hi monocytes migrate into the CNS and further differentiate into antig...
Article
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Introduction: Stroke-associated pneumonia (SAP) is a major cause of mortality in patients who have suffered from severe ischemic stroke. Although multifactorial in nature, stroke-induced immunosuppression plays a key role in the development of SAP. Previous studies using a murine model of transient middle cerebral artery occlusion (tMCAO) have sho...
Article
Full-text available
Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of CD4+ T cells that target autoantigens of the central nervous system (CNS) and their infiltration into the...
Chapter
Interleukin-2 (IL-2), IL-4, IL-7, IL-15, and IL-21 are members of a family of type I cytokines that share the common cytokine receptor γ chain, γc, as a critical receptor component. The gene encoding γc, IL2RG, is mutated in humans with X-linked severe combined immunodeficiency, a profound inherited disease characterized by nonfunctional B cells an...
Article
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IL-21 is a type I cytokine produced by T cells and natural killer T cells that has pleiotropic actions on a wide range of immune and non-immune cell types. Since its discovery in 2000, extensive studies on the biological actions of IL-21 have been performed in vitro and in vivo. Recent reports describing patients with primary immunodeficiency cause...
Article
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IL-1β is a proinflammatory cytokine important for local and systemic immunity. However, aberrant production of this cytokine is implicated in pathogenic mechanisms of a number of inflammatory diseases, including Behçet's disease and age-related macular degeneration. In this study, we report the increased secretion of IL-1β in the retina by neutroph...
Article
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The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not i...
Article
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IL-21 is a type I cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signa...
Article
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Interleukin-21 (IL-21) has broad actions on T and B cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding c...
Article
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IL-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of B cells, increased Ig production, and the development of Th17 and T follicular helper cells. IL-21 is also implicated in the development of autoimmune disease and has antitumor activity. In this study, we investigated the role of IL-21 in host defense to pneumonia v...
Article
Peanut sensitization in diacylglycerol kinase zeta (DGKζ) deficient mice led to elevated peanut-IgE levels and severe anaphylaxis. DGKζ deficient CD4 + T cells did not account for the phenotype. Future studies will determine which immune lineage caused increased food hypersensitivity.
Article
Full-text available
The engagement of TCR induces T-cell activation, which initiates multiple characteristic changes such as increase in cell size, cell division, and the production of cytokines and other effector molecules. The mammalian target of rapamycin (mTOR) regulates protein synthesis, transcription, cell survival, and autophagy. Critical roles of mTOR in T-ce...
Article
We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC(50) values of 32.02 microM and 1.39 microM, respectively. SC...
Article
1alpha,25-Dihydroxyvitamin D(3) (VD(3)), the biologically active form of vitamin D, may have either pro- or anti-inflammatory activities because of its diverse actions on nuclear factor kappa B (NF-kappaB). Previous studies indicated that VD(3) can either activate or inhibit NF-kappaB via Akt-induced I kappaB alpha phosphorylation and increase in I...
Article
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Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosphatidic acid (PA), the physiologic functions of which have been poorly defined. We report here that DGK α and ζ synergistically promote T cell maturation in the thymus. Absence of both DGKα and ζ (DGKα−/−ζ−/−) results in a severe decrease in the number of CD4⁺CD8⁻...
Article
Both diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers involved in signal transduction from many immune cell receptors and can be generated and metabolized through multiple mechanisms. Recent studies indicate that diacylglycerol kinases (DGKs), the enzymes that catalyze phosphorylation of DAG to produce PA, play critic...
Article
Thin CR-39 detectors (with thickness of ) were prepared from commercially available CR-39 SSNTDs through chemical etching in 1 N NaOH/ethanol at . Custom-made petri dishes, with a hole drilled at the bottom and covered with a piece of thin CR-39 detector, were used for culturing HeLa cells. Alpha particles (from an 241Am source) were irradiated fro...
Article
In the present work, we have studied the feasibility of a method based on polyallyldiglycol-carbonate (PADC) films to investigate the effects of alpha particles on HeLa cervix cancer cells. Thin PADC films with thickness of about 20 mum were prepared from commercially available CR-39 films by chemical etching to fabricate custom-made petri dishes f...
Article
1,25-dihydroxyvitamin D(3) (VD(3)) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-kappaB) activity. Here we report a time-dependent biphasic regulation of NF-kappaB in VD(3)-treated HL-60 leukemia cells. After VD(3) treatment there was an earl...
Article
The mis-regulation of nuclear factor-kappa B (NF-kappaB) signal pathway is involved in a variety of inflammatory diseases that leds to the production of inflammatory mediators. Our studies using human U937 promonocytes cells suggested that magnolol, a low molecular weight lignan isolated from the medicinal plant Magnolia officinalis, differentially...
Article
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Recent studies have shown that dibenzocyclooctadiene lignans may reverse P-glycoprotein-mediated multidrug resistance (Pgp-MDR) in cancer cells; however, the mechanism of action remains unknown. Through screening of herbs, we found that schisandrol A (SCH) isolated from Fructus Schisandrae (the dried fruit of Schisandra chinensis (Turcz.) Baill.) s...
Article
Full-text available
Through an extensive herbal drug screening program, we found that gomisin A, a dibenzocyclooctadiene compound isolated from Schisandra chinensis, reversed multidrug resistance (MDR) in Pgp-overexpressing HepG2-DR cells. Gomisin A was relatively non-toxic but without altering Pgp expression, it restored the cytotoxic actions of anticancer drugs such...
Article
Triptolide, a bioactive component of the Chinese medicinal herb Tripterygium wilfordii Hook F., induces p53-mediated apoptosis in cancer cells. This study demonstrated that triptolide activated an alternative p53-independent apoptotic pathway in HL-60 cells. In the absence of an intact p53 and without changing Bax level, at nM range triptolide indu...
Article
Honokiol, a small molecular weight lignan originally isolated from Magnolia officinalis, shows anti-angiogenic, anti-invasive and anti-proliferative activities in a variety of cancers. In this study, we investigated whether honokiol affects the transcription factor nuclear factor-kappa B (NF-κB) which controls a large number of genes involved in an...
Article
Herbal drugs were screened for their activity in reversing multidrug resistance (MDR) in P-glycoprotein (P-gp) over-expressing cancer cells. Through bio-assay guided fractionation an active compound was isolated from Rhizoma Alismatis, the underground part of Alisma orientale and the chemical structure of the isolate compound was confirmed by HPLC,...
Article
Betulinic acid (BA) is a pentacyclic triterpene found in a number of medicinal plants and has been shown to cause apoptosis in a number of cell lines. We report here that BA may also have an effect on HL-60 cell differentiation. BA was cytotoxic to HL-60 cells with an IC50 of 5.7 microM after a 72-h treatment. Flow cytometry analysis showed that af...
Article
Betulinic acid (BA) is a pentacyclic triterpene found in a number of medicinal plants and has been shown to cause apoptosis in a number of cell lines. We report here that BA may also have an effect on HL-60 cell differentiation. BA was cytotoxic to HL-60 cells with an IC50 of 5.7 muM after a 72-h treatment. Flow cytometry analysis showed that after...