Faculty Biosketch
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Milton S. Hershey
Medical Center
Penn State College of Medicine
P.O. Box 850,
500 University Drive
Hershey, PA 17033-2390 |
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Samuel Shao-Min Zhang,
MD PhD
Neural and Behavioral Sciences
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Office Information
Phone: 717-531-8480
Mail Code: H109
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Education |
M.D., Henan
Medical College, China
Ph.D., University of Tokyo, Japan
Post-doctoral, Yale School of Medicine, New Haven |
| Primary
Area of Interest |
Molecular Basis
of STATs during
Retina Development
and Pathogenesis
STAT proteins were
originally
identified and
isolated using cell
culture systems that
respond to cytokines
such as interferon.
It is well
established that the
STAT proteins have a
range of essential
functions for
generation and
function of the
immune system. It is
also widely accepted
that STAT proteins
co-evolved with the
innate and adaptive
immunity that
occurred in the
transition from
lower to higher
organisms. Targeted
disruptions of most
STAT proteins in
mouse result in
severe malfunction
of cellular and
hormonal immune
responses without
obvious
developmental
abnormalities. The
exception is STAT3
in which the
knockout is an
embryonic lethal.
Tissue specific
STAT3 disruption
causes several
phenotypes related
to human diseases
such as Crohn's
disease-like
pathogenesis, heart
failure, and severe
inflammation (PNAS
100:1879-84, 2003;
PNAS 100:12929-34,
2003). Growing
experimental
evidences that STAT
pathways are
involved in many
other aspects of
vertebrate
development. It has
been found that
several STAT
proteins are active
during early
mammalian
development (Exp.
Eye Res. 76:421-31,
2003). Recently we
show that STAT3
mediated signaling
is crucial for the
inhibitory function
of CNTF during rod
photoreceptor
development (IOVS
45:2407-12, 2004;
Exp. Eye Res.
81:103-15, 2005),
indicating that STAT
proteins as common
factors have
specific roles on
specific cell types.
To understand their
tissue specific
functions, we use
retina as a model to
study STAT function
in neuron and glia
cells. As part of
this study,
following projects
are on going, 1.
STATs in control of
rod photoreceptor
differentiation; 2.
STATs in protection
of retina neuron
degeneration; and 3.
STATs in control of
reactive M?glia
cells.
Systems
Biological Studies
of Retina
Development and
Functions
The retina is a
well-defined portion
of the central
nervous system (CNS)
that has long been
used as a model for
CNS developmental
and functional
studies. It is
susceptible to a
variety of diseases
that can lead to
vision loss or
complete blindness.
Most of the unique
functions of the
retina depend upon
its tissue-specific
transcript sets,
suggesting that a
systematic
definition of
retinal transcripts
would be an
invaluable approach
to understanding
retinal cell
identities and
functions.
Traditional method
allows functional
relationship only
among few genes, the
development of
microarray
techniques changes
the way to
understand a
biological process
as a whole among the
major genes played.
From 2001 we have
initiated and
generated a set of
expressed sequence
tags (ESTs) from a
serial of mouse
retina libraries by
collaborated with
Dr. Bento Soares .
About 30,000 clones
have been sequenced
and 12,000 clones
are collected as a
non-redundant EST
set. We have
generated a
comprehensive mouse
retina transcriptome
based on 81,000
murine retina
transcripts from
whole mouse ESTs .
About 33,000
sequence-unique
retina transcript
clusters (RTCs) have
been identified and
the highest-grade
retina-enriched pool
covered almost all
the known genes in
phototransduction
processes that
involved in human
retina diseases,
suggesting the
potential of gene
discoveries for
human retina
disorders (BMC
genomics 6:40,
2005). Meanwhile, we
have also generated
mouse retina
specific cDNA
microarray that
represented about
10,000 UniGene
clusters for
studying the
biological process
during retina
development or
downstream network
alternatives by gene
targeting in mouse
retina. Integrated
biological and
computational
methods, our goal is
to understand the
gene regulation
network during
retina development
and pathogenesis.
Within this overall
project, following
projects are on
going, 1. Functional
genomic studies
during retina
development and
pathogenesis using
retina specific
microarray; 2.
Bioinformatic data
meaning of gene
regulation during
retina development;
and 3. Computational
analysis of specific
evolutionary
conserved genes
during retina
development. |
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