Dr. Dorothy Schafer

Dr. Dorothy Schafer was the recipient of the 2010 Marian Kies Award. Dorothy graduated from the PhD program in biomedical sciences at the University of Connecticut Health Center in 2008. Her graduate work was performed in the laboratory of Dr. Matthew Rasband.

Dorothy's thesis work was concentrated on the development and maintenance of polarized domains along the axon, the axon initial segment (AIS) and node of Ranvier. These axonal domains are necessary for initiation and propagation of the fundamental principle underlying proper nervous system function, the action potential. The focus of Dorothy's thesis work can be divided into three distinct aspects or aims related to the AIS and node of Ranvier: 1) formation during nervous system development, 2) identification of additional molecular components, and 3) mechanisms of disassembly and reassembly following nervous system injury. The ultimate goal of Dorothy's thesis work was to use insights from each of the three aims to better understand how disruptions of the AIS and node contribute to the underlying mechanisms of nervous system dysfunction following injury and during disease. 
The first aspect of Dorothy's thesis aimed to better understand mechanisms of polarized domain assembly during nervous system development and reassembly following injury. In particular, Dorothy focused on how high densities of voltage-gated sodium (Nav) channels cluster at nodes of Ranvier and how lipid-rich microdomains (i.e. lipid rafts) concentrated in the paranodal region contribute to the development and maintenance of Nav channel clusters.
Following her work studying development of the node of Ranvier, Dorothy worked to identify two previously unidentified components of the paranodal junction. Specifically, she and her colleagues identified three novel cytoskeletal components of the paranodal junction: ankyrin B, βII spectrin, and αII spectrin.
The final aspect of Dorothy's thesis was a continuation of her work to understand the contribution of the cytoskeleton to axonal domain maintenance following nervous system injury. Following several different CNS injury paradigms, Dorothy discovered that the polarized cytoskeleton associated with the AIS was particularly sensitive to calpain-mediated proteolysis, occurred rapidly following injury induction, resulted in loss of Nav channels at the AIS, and was independent of cell death. Therefore, early and rapid disruption of the AIS was identified as a novel mechanism contributing to dysfunction during early events of nervous system injury and disease.

Dorothy is currently continuing work studying  neuron-glia interactions in the laboratory of Dr. Beth Stevens at Children’s Hospital Boston. In the Steven’s lab, Dorothy is working on the development of another compartmentalized domain of the neuron, the synapse. In particular, she is pursuing the role of microglia and neuro-immune pathways in synapse development.

 

 

 

Created 3/16/10 BF