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Sean Miller

Class 2013
Education BS. Drexel University
Email smill150@jhmi.edu
Mentor

Dr. Jeff Rothstein

Research Interests

Astrocytes are the most abundant cell type in the central nervous system (CNS). They play essential roles in the maintenance and development of the nervous system. Not surprisingly, disturbances to these roles have been shown to contribute to and affect various neurological disorders in both human patients and animal models. Historically, astrocytes are broadly defined into two subgroups: protoplasmic and fibrous, based on their morphological and anatomical depictions. However, over the years there is a growing appreciation for further astrocyte diversity consisting of astrocyte subpopulations. Much of our current knowledge comes from insight provided by positional identity of the spinal cord, where different anatomical locations contain different astrocyte populations. Within each of these subpopulations is a unique transcriptome and proteome profile that allows the cell to maintain its physiological niche. However, we currently lack a collection of markers to identify subgroups in the adult CNS making it nearly impossible to study different populations in health and disease.

Recently, our group generated a novel transgenic mouse model that selectively labels an astrocyte subset with tdTomato-fluorescence. The direction of my thesis work is to further characterize this unique subset in the adult cortex and spinal cord. Thus far, I have performed extensive transcriptome and proteome profiling, multiphoton in vivo imaging of the adult mouse cortex, and a wide array of other techniques. In doing so, I have discovered that this astrocyte subset has a distinct molecular profile compared to other grey matter astrocytes. Furthermore, I have begun to identify candidate markers that can be used to identify this cell population in other contexts including the human brain. These studies are among the first in astrocyte-research to establish a combinatorial profile for a particular adult astrocyte subset. Lastly, my functional work has begun to shed light on their physiological importance in the CNS and their impact in neurological disorders such as ALS.

Publications

Vorobyeva A. et al. Cyclopamine modulates gamma-secretase mediated cleavage of amyloid precursor protein by altering its subcellular trafficking and lysosomal degradation. Journal of Biological Chemistry 2014 doi:10.1074/jbc.M114.591792

Zhang K. et al. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 2015 doi:10.1038/nature14973

Choi S. et al. Adult hippocampal neurogenesis plays a critical role in neurodegeneration and cognition in alzheimer’s disease. In submission.

Miller S.J. et al. Characterization and identification of a novel astrocyte subtype in the adult CNS. In submission.