Dr. Carter’s research focuses on the signaling mechanisms regulating neuronal survival during the development of the mammalian nervous system. His lab is focused on two projects:

I. Molecular mechanisms of neurotrophin signaling
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 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 target tissues to which the neurons project produce members of this family of trophic factors. The neurotrophins promote neuronal survival and differentiation through binding to the Trks, a family of tyrosine kinase receptors, and induce apoptosis through a 75kD receptor, p75. While significant progress has been made in elucidating the mechanisms by which the Trks promote survival, much less is known about how p75 induces cell death. Carter lab members recently discovered that pro-death ligands promote p75 cleavage by γ-secretase, which releases a transcription factor, NRIF, to enter the nucleus. This process is required for the receptor's apoptotic signal. This research will reveal the mechanisms underlying normal mammalian neural development and function. Moreover, understanding the regulation of neural cell survival is essential for developing therapeutic strategies for neuropathologies involving apoptosis, which include many diseases and nerve lesions.

II. 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 yet to be identified signals from the axon with which the Schwann cells are associated. The overall objective of this project is to elucidate the mechanisms regulating the formation of this essential neural structure. We found that activation of the transcription factor NF-ΚB in Schwann cells is essential for their differentiation into a myelinating phenotype and are currently investigating the up stream activator of NF-ΚB and what the downstream targets are.

RECENT PUBLICATIONS

A novel role for PTEN in the inhibition of neurite outgrowth by myelin-associated glycoprotein in cortical neurons. 2011 Molecular and Cellular Neuroscience 46: 235-244

Eaters of the dead: glial precursors clear neuron corpses during development. 2010 Cell Cycle 9: 1867-1868

Degeneration keeps axons on the straight and narrow. 2010 Nature Neuroscience 13: 526-528

p75 neurotrophin receptor-mediated apoptosis in sympathetic neurons involves a biphasic activation of JNK and up-regulation of tumor necrosis factor-alpha-converting enzyme/ADAM 17. 2010 Journal of Biological Chemistry 285: 20358-20368

Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation. 2010 Journal of Biological Chemistry 16614-16622

The p75 neurotrophin receptor, semaphorins, and sympathetic traffic in the heart.2010 American Journal of Physiology Heart and Circulatory Physiology 298: H1633-1636