Edwin Wan
Contact Information
- Phone
- 304-293-6293
- Address
-
PO Box 9177
64 Medical Center Drive
Morgantown, WV 26506
Research Interests
My laboratory is interested in two areas of research:
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.
Mechanistic study of stroke-induced immune suppression and identification of immune modulatory targets for post-stroke pneumonia
Approximately 30% of stroke patients suffer from post-stroke pneumonia, which is the major cause of mortality from this disease. Recent multi-center clinical studies suggested that prophylactic antibiotic treatments do not reduce the incidence of post-stroke pneumonia nor mortality. Moreover, the emergence of antibiotic resistant bacteria renders the “gold standard” antibiotic treatments ineffective. Therefore, novel therapeutic strategies are needed to improve clinical outcomes.
Using mouse models of focal brain ischemia coupled with Pseudomonas aeruginosa infection, the overall goal of my research is to 1) determine the cellular and molecular profiles of immune cell niches in the lungs after focal brain ischemia induction; 2) elucidate the immune suppressive mechanisms following ischemic stroke event; and 3) identify key cytokines and chemokines that contribute to post-stroke pneumonia.
Overall, this study will elucidate the immune cell types involved and the underlying mechanisms that govern post-stroke pneumonia, with the goal of identifying novel therapeutic targets and improving clinical outcomes.
Recent Publications
Representative Publications:
- Palle P, Monaghan KL, Milne SM, Wan ECK (2017). Cytokine signaling in multiple sclerosis and its therapeutic applications. Medical Sciences 5:0023 doi: 10.3390/medsci5040023.
- Wan CK*, He C*, Sun L, Egwuagu CE, Leonard WJ (2016). Cutting Edge: IL-1 receptor signaling is critical for the development of autoimmune uveitis. Journal of Immunology 196:543-546. (*Co-first authorship)
- Wan CK, Li P, Spolski R, Oh J, Andraski AB, Du N, Yu Z, Dillon CP, Green DR, Leonard WJ (2015). IL-21-mediated non-canonical pathway for IL-1b production in conventional dendritic cells. Nature Communications 6:7988. doi: 10.1038/ncomms8988.
- Wan CK*, Andraski AB*, Spolski R, Li P, Kazemian M, Oh J, Samsel L, Swanson PA II, McGavern DB, Sampaio EP, Freeman AF, Milner JD, Holland SM, Leonard WJ (2015). Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells. PNAS 112:9394-9399. (*Co-first authorship)
- Wan CK, Oh J, Li P, West EE, Wong EA, Andraski AB, Spolski R, Leonard WJ (2013). The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells. Immunity 38:514-527.
- Wan CK*, Carpenter JH, Mousallem T, Boustany RN, Kuan CT, Burks AW, Zhong XP (2008). Synergistic control of T cell development and tumor suppression by diacylglycerol kinase α and ζ. PNAS 105: 11909-11914. (*Co-first authorship)
Book Chapter:
- Wan CK and Leonard WJ (2016). γc family cytokines: role in immune cell development and function. In Michael JH Ratcliffe, Encyclopedia of Immunobiology Volume 2, pp. 509-518. Cambridge, MA: Academic Press.