Edwin Wan, PhD

Associate Professor

Organization:

West Virginia University School of Medicine

Department:

Microbiology, Immunology & Cell Biology

Classification:

Faculty

Associate Professor

Organization:

West Virginia University School of Medicine

Department:

Department of Neuroscience

Classification:

Faculty

Associate Professor

Organization:

West Virginia University School of Medicine

Department:

Rockefeller Neuroscience Institute (SOM)

Classification:

Faculty

• PhD, City University of Hong Kong, 2007

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. 

Member 
WVU Rockefeller Neuroscience Institute

Immunology, Neuroscience

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.