Jianrong Li

Scholarly Interests

The central goal of our research is to understand how oligodendroglial development in the mammalian central nervous system is regulated in health and disease. Specifically, we are interested in molecular and cellular mechanisms involved in oligodendrocyte death as occurring in white matter injuries, such as multiple sclerosis and cerebral palsy. Because in most CNS diseases, multiple cell types including neurons, glial cells and vascular cells are involved via complex interactions, we investigate, at the cellular and molecular level, the role of microglia and astrocytes in modulating oligodendrocyte development, differentiation and cell death. We use a variety of methods including primary cell cultures and transgenic animals to elucidate signal transduction pathways in mediating oligodendrocyte injury. The second focus of our laboratory is to elucidate the signals that promote oligodendrocyte survival and regeneration/remyelination after injury, and to study cell-cell interactions that regulate remyelination. These studies should contribute significantly to our understanding of mechanisms of oligodendrocyte development and injury, and provide new clues for potential prevention and treatment of human white matter diseases. Our third research interest is to explore novel roles of vitamin K in the developing brain. Vitamin K is a cofactor for a single known enzyme, gamma-glutamylcarboxylase that catalyzes the posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid in vitamin K-dependent proteins, such as Gas6. It prevents oxidative injury to oligodendrocytes and neurons. Several lines of evidence suggest an as yet identified role of vitamin K in the developing brain. We will use primary cell cultures and transgenic mice to investigate the physiological roles of vitamin K and the carboxylase in the developing brain.