Vijay
P. Sarthy, PhD
Magerstadt Professor of Ophthalmology
Professor of Cell and Molecular Biology
To Contact Dr. Sarthy:
phone: 312-503-3031
e-mail: vjsarthy@northwestern.edu
Dr. Sarthy's website
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Research Interests
The pattern of gene expression in eukaryotic cells is strongly influenced
by interactions with neighboring cells. When cell-cell interactions are perturbed,
changes in cellular gene activity are often observed. In the vertebrate retina,
inherited or acquired rod and cone degeneration results in disruption of normal
interactions between photoreceptors and their support cells, the Müller
cells. Under these conditions many genes such as the glial intermediate filament
protein (GFAP) gene, ciliary neurotrophic factor (CNTF) gene and basic fibroblast
growth factor (bFGF) gene are upregulated in neighboring Müller cells.
We use techniques such
as single cell RT-PCR and differential display to study changes in gene expression
patterns in Müller cells. A major goal of our current research is to
elucidate the molecular mechanisms responsible for transcriptional activation,
and to determine the extracellular inductive signal and the signal transduction
pathways involved. Our recent cell transfection studies and experiments with
GFAP-lacZ transgenic mice suggest that GFAP gene activation in Müller
cells is regulated by a cell type-specific, inducible enhancer, and that GFAP
gene is activated through the JAK-STAT pathway. The work on gene regulation
is crucial for development of strategies for using Müller cell-specific
promoters to test the biological effects of growth factors and cytokines in
animals models of retinal degeneration, and more importantly for designing
cell type-specific vectors for targeted delivery in gene therapy.
A second project is concerned
with molecular cloning, regulation and function of neurotransmitter transporters
--- a family of membrane proteins that are involved in the uptake of neurotransmitters.
We are particularly interested in the role of taurine and glutamate transporters
in retinal ischemia and glutamate neurotoxicity. We have already cloned and
characterized GABA, taurine and glutamate transporters from retina. We have
also localized the transporters to specific retinal cell types, and shown
that phosphorylation may play a key role in regulating transporter function.