Research
Myelin development and regeneration
Myelin sheaths are essential for the nervous system, playing major roles in electrical conduction, metabolic support, and cognitive and motor function. Myelin disorders like multiple sclerosis affect millions globally and have devastating effects, in part due to failure in myelin regeneration. Our research focuses on understanding the developmental pathways in myelinating cells to identify new strategies that can promote regeneration in the central and peripheral nervous systems.
Key questions:
What mechanisms promote or inhibit myelin formation?
How does myelin contribute to higher nervous system function throughout development?
What strategies can be employed to promote myelin regeneration?
Astrocyte development and reactivity
Astrocytes are dynamic cells that play important roles in CNS development, homeostasis, and injury response. Astrocytes closely interact with neurons and blood vessels via synapse and endfeet respectively, which is critical for sculpting synaptic transmission, neural circuits, and cerebrovascular networks in the central nervous system. Our research focuses on the functions of astrocytes during development and in neurological pathologies such as glioma, stroke, as well as neurodegenerative disorders.
Key questions:
What mechanisms regulate astrocytes’ lineage specification and heterogeneity?
How do astrocytes regulate the blood-brain barrier and injury response?
How do astrocytes contribute to pathogenesis in neurological disorders?
Models of CNS disease and injury
White matter injury
In adults, the most common white matter injury is MS (multiple sclerosis), which can be identified with acute and focal demyelinated lesions. In infants, PVL (periventricular leukomalacia) and HIE (hypoxic ischemic encephalopathy) are typical white matter injuries that present hypomyelination. A key feature of these diseases is that they both display myelin damage (demyelination and hypomyelination respectively), which leads to impaired axonal integrity and function. OLs are responsible for CNS myelination, which is essential for rapid transmission of action potentials and maintaining axonal integrity and health. Injured white matter is populated by “stalled” oligodendrocyte precursor cells (OLPs) that demonstrate exaggerated Wnt signaling and consequently impaired regenerative myelination, suggesting that manipulation of Wnt signaling could provide a means to restore myelinating OLs. Our research focuses on the mechanisms associated with Wnt signaling in OL lineage development and regeneration, and pinpoint potential targetable pathways for white matter disorder.
Ischemic stroke
Ischemic stroke is the 5th leading cause of death in the U.S., and while great strides have been made to reduce mortality and improve patients’ quality of life, it remains difficult to treat stroke-induced neurological damage and brain dysfunction. While damage in the blood-brain barrier (BBB) is one of the hallmark pathology features of stroke, the mechanisms underlying BBB reconstruction after stroke injury are largely unknown. Emerging evidence suggests astrocytes play a pivotal role in BBB reconstruction, but the exact mechanisms remain poorly defined. Our research focuses on key mechanistic pathways by which astrocytes govern BBB recovery after ischemic stroke. We hope our research can lead to discovery of novel glia-specific therapeutic approaches, such as astrocytic metabolism-cytokine coupling, to stimulate brain repair after stroke injury.
Glioma
Malignant glioma is a devastating brain cancer with an extremely poor prognosis. Despite the increasing knowledge of glioma etiology over the past 70 years, the survival rates of patients with malignant glioma have only slightly improved. Glioma is so difficult to treat partly because of the metabolic adaptations, pH dysregulation, and immune suppression in the tumor microenvironments. However, we have yet to fully understand the mechanisms in glioma tumorigenesis and their relevance to glioma therapy. Our research focuses on the mechanisms underlying glioma and tumor microenvironment interaction, and identifies novel, tractable pathways for therapeutic intervention.
