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In the central nervous system (CNS), oligodendrocytes synthesize myelin as an extension of their plasma membranes. The myelin wraps axons and facilitates rapid and efficient conduction of nervous impulses as well as promotes axonal nourishment and protection. Destruction of myelin through injury or disease causes loss of motor and cognitive function. Oligodendrocyte precursors and stem cells remain in the CNS following the pathology and are potentially capable of forming mature oligodendrocytes and then new myelin. However, their maturation is severely limited in many pathological conditions.
The goal of the Grinspan Lab is to identify factors in the CNS that inhibit the development of mature oligodendrocytes both during development and disease. The lab has seen that oxidative stress and inflammation can impede myelination and have identified several families of signaling factors in the CNS that are activated by these processes and interfere with oligodendrocyte development and myelination, including bone morphogenetic proteins and the Wnt/b-catenin family of signaling factors.
The Grinspan Lab uses a variety of approaches including cell culture models, genetic models, and disease models. The lab's studies focus on factors that inhibit myelin regeneration in multiple sclerosis (including the role of lipid regulation), myelin loss and oligodendrocyte dysfunction in HIV-associated neurocognitive deficits (including the role of antiretroviral drugs), and factors that limit myelination in perinatal white matter injury.
- White matter loss in HIV-associated neurocognitive deficits — effects of the virus on oligodendrocytes maturation and survival
- White matter loss in HIV-associated neurocognitive deficits — how antiretroviral drugs affect oligodendrocyte maturation and survival
- The effect of HIV or the antiretroviral drugs on developmental myelination
- Factors which impede development of myelin in perinatal white matter injury
- The role of lipid regulation in the development of myelin and myelin regeneration
Co-Leader, Developmental Biology Research Affinity Group
Dr. Grinspan's research program focuses on oligodendrocytes, cells of the central nervous system that synthesize the myelin sheath required for transmission of nervous impulses. Her research seeks to understand the signaling pathways that regulate oligodendrocyte maturation and how they are perturbed in diseases such as multiple sclerosis, HIV, and perinatal white matter injury.