Our Research

Developing Treatments for Neuroinflammatory Diseases

Research Focus

Neuroinflammation plays a pivotal role in the pathogenesis of many CNS disorders, including ischemic stroke and multiple sclerosis (MS). The primary focus of our research is to understand cellular and molecular mechanisms of ischemic stroke and MS-evoked neuroinflammation using animal models of transient middle cerebral ischemia/reperfusion (tMCAO/R) and experimental autoimmune encephalomyelitis (EAE), respectively. We are also developing novel therapies for the treatment of these neuroinflammatory diseases. We have identified IFNβ, an FDA approved MS treatment, exerts potent immunomodulatory properties and is capable of alleviating neuroinflammation in ischemic stroke. This study is currently supported by a NIH R01 grant.

Research Projects

Ischemic Stroke Project

IFNβ is an FDA approved agent for MS treatment, and its anti-inflammatory properties were reported by us and other groups. Recently, we successively demonstrated that IFNβ confers a protective effect against ischemic stroke through a modulatory effect on neuroinflammation in the ischemic brain of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) animals [a]. With regard to our ischemic stroke research, my lab is interested in developing anti-inflammatory therapies that can be combined with tissue plasminogen activator (tPA) treatment. tPA, the only FDA-approved therapy for ischemic stroke, functions to restore cerebral blood flow by dissolving blood clots. However, tPA does not offer any protective effects for ischemia-induced neuroinflammation, and it increases the risk of hemorrhagic transformation (HT) that further damages the ischemic brain. Our positive and solid results encourage us to further investigate the  treatment that combines IFNβ and tPA in ischemic stroke, with the purpose of lessening the adverse effects of tPA and extending the tPA therapeutic window by IFNβ. We propose that the administration of IFNβ in delayed tPA-treated ischemic stroke may ameliorate ischemia-, reperfusion-, tPA-induced neuroinflammation, and lessen delayed tPA-induced HT in the ischemic brain.  


Multiple Sclerosis (MS) Project

Our lab has identified a novel therapeutic agent, D3T, with anti-inflammatory properties [b] and has demonstrated its ant-inflammatory effects on the suppression of peripheral and CNS immune cell activation, as well as the amelioration of EAE [c]. Further investigation of its effect on the prevention of inflammation-induced demyelination, which causes the neurological deficits in the disease, is ongoing.


Alzheimer's Disease (AD) Project 

Unusual aggregation of proteins, including Aβ plaques outside the cells and tau tangles inside the neurons, marks the brains of AD patients. Moreover, it has been demonstrated that neuroinflammation plays a pivotal role in AD development and progression. Microglia has been documented to be a major cell type triggering and exacerbating neuroinflammation, and its activation during neuroinflammation causes neuronal damage leading to declined brain cognitive function. Recently, a unique microglia type that is associated with restricting developing of AD has been shown. Single-cell RNA-seq has revealed a novel microglia type, named disease-associated microglia (DAM) in Alzheimer's model. DAM are Alzheimer's disease associated phagocytic cells conserved in mice and human, and are activated sequentially by Trem2-independent and -dependent pathways. Our lab is investigating whether alleviating neuroinflammation through pharmacological approach would ameliorate AD-associated CNS pathology.  


References 

a. P-C. Kuo, B. A. Scofield, I-C. Yu, F-L. Chang, D. Ganea, and J-H. Yen. Interferon beta modulates inflammatory response in cerebral ischemia. 2016. J Am Heart Assoc. 8(5):1-15. JAHA.115.002610.

b. D. A. Brown, S. Betharia, J-H. Yen, Q. Tran, H. Mistry, and K. Smith. Synthesis and structure-activity relationships study of dithiolethiones as inducers of glutathione in the SH-SY5Y neuroblastoma cell line. 2014. Bioorganic & Medicinal Chemistry Letters. 24(2014):5829-5831

c. P-C. Kuo, D. A. Brown, B. A. Scofield, I-C. Yu, F-L. Chang, P-Y. Wang, and J-H. Yen. 3H-1, 2-dithiole-3-thione as a novel therapeutic agent for the treatment of experimental autoimmune encephalomyelitis. 2016. Brain, Behavior, and Immunity. 57(2016): 173-186

Major Research Equipment available for the Research Team

10x Genomics               BD FACSVerse Analyzer        BD FACSMelody Cell Sorter     OLYMPUS FV300

Our Research Supported by

YEN Lab at IUSM © 2013-2023
Powered by Webnode
Create your website for free! This website was made with Webnode. Create your own for free today! Get started