Carter, Bruce D., Department of Biochemistry
Bruce D. Carter, Ph.D.
Department of Biochemistry
Center for Molecular Neuroscience
418 Medical Research Building-II
I. Mechanisms of neurotrophin signaling through the p75 receptor: Our lab studies the signaling mechanisms regulating neuronal survival. Programmed cell death in the nervous system is a naturally occurring process in mammalian development; however, abnormal apoptosis is the basis for many neuropathologies, e.g. Alzheimer’s and Parkinson”s disease and ischemic injury. The delicate balance between neuronal survival and death is regulated, in part, by a family of growth factors referred to as the neurotrophins. The neurotrophins promote neuronal survival and differentiation through binding to the Trks, a family of tyrosine kinase receptors. Interestingly they also can induce apoptosis and degeneration through the p75 receptor, a member of the TNF receptor family. We have discovered a number of signaling pathways regulated by the p75 receptor and one of our research goals is to further delineate the molecular mechanisms by which it functions using a number of molecular, cellular and in vivo approaches.
II. Process by which apoptotic neurons are phagocytosed: Following the extensive apoptosis that occurs during development of the nervous system, the resulting neuronal corpses must be efficiently removed to prevent an inflammatory response, which can eventually lead to neurodegeneration. Unfortunately, the molecular mechanisms underlying this phagocytic process in the nervous system are poorly understood. We recently demonstrated that satellite glial precursor cells are the primary phagocytes that engulf the many neuronal corpses in the developing dorsal root ganglia and identified a novel engulfment receptor, Jedi1, as mediating this engulfment. Current efforts are aimed at determining the mechanisms by which Jedi1 signals engulfment and investigating its role in regulating phagocytosis in other regions of the developing and mature nervous system.
III. Molecular mechanisms of myelin formation: Myelin is a multilamellar structure that ensheaths axons and allows for the rapid conduction of electrical signals, acts as a protective barrier for axons, regulates regeneration and provides trophic support for neurons. This structure is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the CNS. The formation of peripheral myelin during development is initiated by carefully orchestrated signaling between Schwann cells and their associated axons, but the mechanisms underlying this intercellular communication remain poorly understood. The overall objective of this project is to elucidate the mechanisms regulating the formation of this essential neural structure. We have identified a number of signaling pathways in Schwann cells that are critical for their differentiation into a myelinating phenotype and are currently investigating the regulation of these signals in normal development and in models of demyelinating neuropathies.
For more information, please visit the lab website.