Oligodendrocytes are the myelin-producing glial cells, which mediate rapid neuronal conduction and provides trophic/metabolic support of axons. These glia cells produce a vast amount of myelin membrane and thus are particularly sensitive to cellular homeostatic changes that result from diverse stresses, including CNS inflammation. There is an increasing recognition that inflammation plays a critical role in the multiple sclerosis, neurodegenerative diseases, or injury such as trauma or stroke. The primary focus of our lab is to understand the cytoprotective pathways of oligodendrocytes against neuroinflammation and the impact of oligodendrocyte protection on the progression of neurological disorders.
Multiple sclerosis and oligodendrocytes
We are particularly interested in multiple sclerosis (MS), which is one of the best-characterized autoimmune demyelinating disorders that is frequently diagnosed in young adults. Recent studies indicate that oligodendrocyte apoptosis and subsequent axon degeneration are key attributes of MS progression. Protection of oligodendrocytes will allow for the preservation of myelin production and promote myelin repair, which likely to have significant therapeutic value for MS patients. We are interested in exploring the underlying mechanisms involved in oligodendrocyte stress from inflammation and uncovering the potential cytoprotective responses in well-established mouse models of MS. |
Adaptive responses and oligodendrocytes
Activation of the unfolded protein response (UPR) pathways has been reported in the CNS lesions of MS and its preclinical animal model. Upon activation of the UPR, cell protective mechanisms are initiated by reducing the protein load on the endoplasmic reticulum, while upregulating a set of chaperones and protective protein. Our previous findings show that enhancement of the one arm of the UPR protects oligodendrocytes in response to CNS inflammation. We strive to expand upon our previous findings to explore the impact of other arms of the UPR on oligodendrocyte survival and disease progression in animal models. Interestingly, the UPR pathways have been implicated in the regulation of autophagy, which is crucial in protein degradation and homeostasis maintenance. It has been suggested that autophagy is important in maintaining oligodendrocyte differentiation and homeostasis. We are interested in investigating whether UPR-enhanced oligodendrocyte protection is associated with augmented autophagy.
Activation of the unfolded protein response (UPR) pathways has been reported in the CNS lesions of MS and its preclinical animal model. Upon activation of the UPR, cell protective mechanisms are initiated by reducing the protein load on the endoplasmic reticulum, while upregulating a set of chaperones and protective protein. Our previous findings show that enhancement of the one arm of the UPR protects oligodendrocytes in response to CNS inflammation. We strive to expand upon our previous findings to explore the impact of other arms of the UPR on oligodendrocyte survival and disease progression in animal models. Interestingly, the UPR pathways have been implicated in the regulation of autophagy, which is crucial in protein degradation and homeostasis maintenance. It has been suggested that autophagy is important in maintaining oligodendrocyte differentiation and homeostasis. We are interested in investigating whether UPR-enhanced oligodendrocyte protection is associated with augmented autophagy.
Therapeutic compounds
Although current immunomodulatory therapies for MS can reduce the frequency and severity of relapses, they have demonstrated limited impact on the progression of disease. Complementary strategies are therefore urgently needed to protect and/or repair the CNS to halt or slow down the progression of MS. In collaboration with the labs of Dr. Jeffery Kelly and Dr. Luke Wiseman at the Scripps Research Institute, we are measuring the therapeutic effects of small chemical compounds that are designed to enhance adaptive protective responses in oligodendrocytes in mouse models of MS. With these efforts, we are hoping to promote defining the therapeutic potentials of new compounds for promoting functional recovery of patients.
Although current immunomodulatory therapies for MS can reduce the frequency and severity of relapses, they have demonstrated limited impact on the progression of disease. Complementary strategies are therefore urgently needed to protect and/or repair the CNS to halt or slow down the progression of MS. In collaboration with the labs of Dr. Jeffery Kelly and Dr. Luke Wiseman at the Scripps Research Institute, we are measuring the therapeutic effects of small chemical compounds that are designed to enhance adaptive protective responses in oligodendrocytes in mouse models of MS. With these efforts, we are hoping to promote defining the therapeutic potentials of new compounds for promoting functional recovery of patients.