A headshot photo of Edwin Wan.

Edwin Wan, PhD

Associate Professor

Contact Information

Phone
304-293-6293
Address
PO Box 9177
64 Medical Center Drive
Morgantown, WV 26506

Affiliations

  • Department of Microbiology, Immunology, & Cell Biology
  • Department of Neuroscience
  • Rockefeller Neuroscience Institute

Graduate Training

  • Cancer Immunology & Pharmacology, City University of Hong Kong

Fellowships

  • Immunology, National Institutes of Health
  • Immunology, Duke University Medical Center

Research Interests

My laboratory is interested in two areas of research:

1. Elucidating the role of cytokine signaling in the pathogenesis of multiple sclerosis

Our immune system needs to be in a perfect balance for keeping us healthy, and this balance is maintained by a group of proteins named “cytokines”. Cytokines are signaling molecules used to communicate between various immune cell types, which are critical not only for their development, but also for ensuring proper immune responses are triggered when required. An active, responsive immune system is certainly important as patients with immunodeficiency often develop cancers, and are frequently subjected to infections. However, excessive immune responses are also not desirable, as they would lead to immunopathology. Examples are autoimmune diseases caused by over-reactive immune cells that recognize and attack our own body.

Multiple sclerosis (MS) is an autoimmune disease that the over-reactive immune cells attack the central nervous system (CNS). This attack causes severe inflammation, leading to irreversible damages of the CNS. Current therapeutic strategies aimed to reduce the frequency of relapses (attacks) but are unable to cure the disease. Improper production of certain cytokines, such as GM-CSF, IL-17 and IL-23 significantly correlates with the pathogenesis of MS but exactly how they do it, particularly what immune cell types and signaling pathways involved are not well defined. The overall goal of my research is to 1) identify cytokines and underlying mechanisms that govern the pathogenesis of multiple sclerosis, and neuroinflammation in general, using pre-clinical animal models; 2) explore novel inhibitors that target signaling molecules responsible for triggering neuroinflammation by high throughput screening; and 3) decipher gene expression profiles and functional abnormality of immune cells isolated from MS patients.

These studies will not only improve our understanding on how improper control of immune cell activation leads to neuroinflammation, but also have potential clinical impacts on MS treatments.

2. Immune-glial cell interactions in brain recovery following ischemic stroke

Current treatment options for patients experienced ischemic stroke allow blood reperfusion to the brain but fails to resolve the neurological deficits, which cause long-term physical and cognitive disabilities in stroke survivors. Thus, novel therapeutic strategies for improving brain recovery and resolving neurological deficits are critically needed. Neuronal death induces the activation of microglia that express proinflammatory mediators, leading to the exacerbation of brain damage following ischemic stroke. Thus, targeting microglia was thought to ameliorate brain injury post-stroke. However, recent studies have shown that the elimination of microglia increases the size of brain infarct and worsens the neurological deficits of mice following transient middle cerebral artery occlusion (tMCAO), an animal model for ischemic stroke studies. These data suggest a functional heterogeneity of microglia in response to ischemic insults, or a temporal phenotypic shift of microglia from neurotoxic to neuroprotective over time following ischemic injury. Our overall research goal is to investigate whether the CD11c- mediated signaling potentiates these diverse functions or phenotypical shift in microglia, and to determine the potential neuroprotective role of CD11c+ microglia in brain recovery following ischemic stroke.

CD11c is an integrin alpha chain protein that is widely used as a defining marker for conventional dendritic cells (cDCs). CD11c regulates cell adhesion, migration, and phagocytic activity of cDCs. The role of CD11c-mediated signaling in microglia following ischemic stroke is not known. Transcriptome analysis suggests that CD11c+ microglia may play a protective role following neurological insults, but experimental evidence to support this notion is lacking. Elucidating the mechanisms by which microglia switch from proinflammatory to neuroprotective can help develop novel strategies that promote neurological recovery following ischemic stroke.

Recent Publications

1. Spolski R, Li P, Chandra V, Shin B, Goel S, Sakamoto K, Liu C, Oh J, Ren M, Enomoto Y, West EE, Christensen SM, Wan ECK, Ge M, Lin JX, Yan B, Kazemian M, Yu ZX, Nagao K, Vijayanand P, Rothenberg EV, Leonard WJ (2023). Distinct use of super-enhancer elements controls cell type-specific CD25 transcription and function. Science Immunology 8 (89) doi:10.1126/sciimmunol.adi8217. 

2. Mihalik NE, Steinberger KJ, Stevens AM, Bobko AA, Hoblitzell EH, Tseytlin O, Akhter H, Dziadowicz SA, Wang L, O’Connell RC, Monaghan KL, Hu G, Mo X, Khramtsov VV, Tseytlin M, Driesschaert B, Wan ECK#, Eubank TD# (2023). Dose-specific intratumoral GM-CSF modulates breast tumor oxygenation and antitumor immunity. The Journal of Immunology 211: 1589-1604 doi:10.4049/jimmunol.2300326. (#Corresponding author)
 
3. Monaghan KL, Zheng W, Akhter H, Wang L, Ammer AG, Li P, Lin JX, Hu G, Leonard WJ, Wan ECK# (2023). Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice. Frontiers in Immunology 14:1117828 doi:10.3389/fimmu.2023.1117828. (#Corresponding author)
 
4. Monaghan KL, Aesoph D, Ammer AG, Zheng W, Rahimpour S, Farris BY, Spinner CA, Li P, Lin JX, Yu ZX, Lazarevic V, Hu G, Leonard WJ#, Wan ECK# (2021). Tetramerization of STAT5 promotes autoimmune-mediated neuroinflammation. PNAS 118 (52) e2116256118 doi:10.1073/pnas.2116256118. (#Corresponding author)
 
5. Engler-Chiurazzi E, Monaghan KL, Wan ECK, Ren X (2020). Role of B cells and the aging brain in stroke recovery and treatment. GeroScience doi:10.1007/s11357-020-00242-9. 
 
6. Monaghan KL*, Farris BY*, Zheng W, Wan ECK# (2020). Characterization of immune cells and proinflammatory mediators in the pulmonary environment. Journal of Visualized Experiments 160, e61359 doi:10.3791/61359. (*Co-first authorship; #Corresponding author)
 
7. Monaghan KL, Wan ECK# (2020). The role of granulocyte-macrophage colony-stimulating factor in murine models of multiple sclerosis. Cells 9:611 doi:10.3390/cells9030611. (#Corresponding author)
 
8. Yang J, Wang HX, Xie J, Li L, Wang J, Wan ECK, Zhong XP (2020). DGK a and z activities control TH1 and TH17 cell differentiation. Frontiers in Immunology 10:3048 doi:10.3389/fimmu.2019.03048.
 
9. Pan Y, Deng W, Xie J, Zhang S, Wan ECK, Li L, Tao H, Hu Z, Chen Y, Ma L, Gao J, Zhong XP (2020). Graded diacylglycerol kinases  and activities ensure mucosal-associated invariant T cell development. European Journal of Immunology 50:192-204 doi:10.1002/eji.201948289.
 
10. Monaghan KL, Zheng W, Hu G#, Wan ECK# (2019). Monocytes and monocyte-derived antigen-presenting cells have distinct gene signatures in experimental model of multiple sclerosis. Frontiers in Immunology 10:2779 doi:10.3389/fimmu.2019.02779. (#Corresponding author)
 
11. Farris BY, Monaghan KL, Zheng W, Amend CD, Hu H, Ammer AG, Coad JE, Ren X, Wan ECK# (2019). Ischemic stroke alters immune cell niche and chemokine profile in mice independent of spontaneous bacterial infection. Immunity, Inflammation and Disease 7:326-341 doi:10.1002/iid3.277. (#Corresponding author)
 
12. Palle P*, Monaghan KL*, Milne SM, Wan ECK# (2017). Cytokine signaling in multiple sclerosis and its therapeutic applications. Medical Sciences 5:23 doi:10.3390/medsci5040023. (*Co-first authorship; #Corresponding author)