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Education
‧ BSc. in Chemical Engineering, National Tsing Hua University
1985-1989
‧ Ph.D. in Bioengineering, University of Illinois at Chicago
1994-2000
‧ Postdoc. in Division of Hematology, Stanford University
2000-2004
Introduction
When I received my PhD degree in Bioengineering from University
of Illinois at Chicago (Advisor: Dr. Steven Olson), I was
looking for a challenging research opportunity in the field of
genomics so I can learn something new and different from my
previous training in chemical/protein engineering, enzyme
kinetics and structural biology. Fortunately, I was able to
explore the area of bioinformatics at the Division of Hematology
of Stanford University (PI: Dr. Lawrence Leung). Since then, I
have used two gene expression-profiling approaches (cDNA
microarray and Serial Analysis of Gene Expression) on studies of
endothelial cell dysfunction and vascular wall biology. During
that time, I recognized the fact that no matter what we have
discovered at the gene expression level, it is critical to
investigate the gene’s product at the protein level to address
the significance of that gene’s function. One needs to develop
studies at both the transcriptional and the translational levels
before he or she can comprehensively learn the function and
mechanism of the genes of interest. Consequently, I concluded
that I should approach my study using the structural-functional
analysis of proteins while continuing to pursue my research
interests in bioinformatics. It is my goal to pursue a research
path that can combine these two disciplines together. I plan to
focus my studies in the field of the thrombosis, vascular
biology, novel drug discovery/design, and biomedical
applications of protein engineering.
Research interests
I. Endothelial dysfunction in
Cardiovascular and thromboembolic disease
While the pathogenesis of cardiovascular and thromboembolic
diseases have been under intensive investigation for many years,
there is still much to learn as new questions continue to arise
from various directions. An important observation is that
endothelial dysfunction is a commonly found indication among
these diseases regardless of it being the cause or the
consequence. Examples are the localized vascular lesions and
sclerosis, leakage in the blood-brain barriers, and the blood
flow obstruction in various vascular beds. Therefore, a better
understanding of the cellular and molecular components of the
endothelial cells that contribute to the regulation of critical
vascular functions is important and may lead to the development
of novel drugs and therapies for such diseases.
II. Novel markers and modulators of the
peripheral circulation and vasculature
The derivation of vascular heterogeneity is multifaceted,
beginning when the nascent vasculature is laid down in the
embryo. Recent insights have led to a model of vascular
formation that incorporates several known vascular-specific
growth factors. According to this model, the first characterized
vascular-specific growth factor, VEGF, maintains its position as
the most critical driver of vascular formation, as it is
required to initiate the formation of immature vessels by
vasculogenesis or angiogenic sprouting, during development as
well as in the adult. Furthermore, structural and functional
changes occur during organogenesis, driven by genetic,
environmental, hormonal, hematological and tissue specific
factors, eventually resulting in the formation of the mature
vessels. Up to now, most vascular studies have focused primarily
on the arterial side of the circulation, fewer have addressed
the venous side and, fewer still, have addressed the
microvascular circulation. Therefore, the understanding of the
endothelium functional heterogeneity of the peripheral
circulation and vasculature and how each vascular subtype
responds differentially under diseased or normal physiological
conditions has become one of my major interests.
III. Umbilical cord blood stem cells
Umbilical cord blood is an alternative source of hematopoiteic
stem cells from bone marrow that has recently been tested in
both child and adult cancer patients. Compared with adult
peripheral blood or bone marrow, umbilical cord blood contains a
greater proportion of highly proliferative hematopoitetic stem
cells. Although the exact reason of why these progenitor cells
are present in the umbilical cord blood of newborns is unknown,
it has been explained by the placental production of numerous
growth factors, such as granulocyte colony-stimulating factor
(G-CSF), which is know to mobilize hematopoitetic stem cells in
vitro. Most hematopoitetic stem cells therapies, such as gene
therapy, hematopoitetic stem cell expansion, purification, and
purging involve ex vivo manipulation. However, it has been
difficulty to develop effective cell culture protocols for
hematopoitetic stem cells. Until recently, there has been little
knowledge of the heterogeneity that exists in the human
hematopoitetic stem cell pool and the conditions of ex vivo
culturing that can affect the various hematopoitetic stem cell
classes. Moreover, therapies designed for different diseases
must target a subpopulation of the hematopoitetic stem cells
with specific properties. The success of these therapies depends
on our understanding in the mechanisms by which hematopoitetic
stem cells undergo appropriate molecular direction to initiate
their mobilization, proliferation and differentiation.
Therefore, the understanding of the composition of the
hematopoietic stem cells pool in humans and how ex vivo
manipulation can be done to differentially affect the various
hematopoitetic stem cell classes in a controlled manner for
scientific and clinical applications.
Papers Published within last 5 years
Antiangiogenic antithrombin induces global changes in the gene
expression profile of endothelial cells. Chang, WQ., Chuang,
Y-J., Jin, TQ., Swanson, R., Xiong, Y., Leung, L., Olson, ST.
Cancer Research, 2006, 66:10, P5047-5055.
Antiangiogenic antithrombin down-regulates the expression of the
pro-angiogenic heparin sulfate proteoglycan, perlecan, in
endothelial cells. Zhang, WQ, Chuang YJ, Swanson R, Li J, Seo K,
Leung L, Lau L and Olson ST, Blood, 2004, 104:3, P1185-1191.
Dramatic acceleration of anithrombin inhibitor of factor IXa by
heparin to physiological relevant rates depends on calcium ions
and exosite interactions. Bessted T, Swanson R, Chuang YJ, Bock
PE, Bjork I, and Olson ST, Biochemisty, 2003, 42, P8183-8162.
Heparin activates antithrombin anticoagulant function by
generating new interaction sites (exosites) for blood clotting
proteinases. Olson, S.T., Chuang YJ, Trends in Cardiovascular
Medicine, 2002, 12, P331-338.
The antithrombin P1 residue is important for target proteinase
specificity but not for heparin activation of the serpin.
Characterization of P1 antithrombin variants with altered
proteinase specificity but normal heparin activation. Yung-Jen
Chuang, Richard Swanson, Srikumar M. Raja, Susan C. Bock, and
Steven T. Olson, Biochemistry, 2001; 40 (22): P6670-6679.
Heparin enhances the specificity of antithrombin for thrombin
and factor Xa independent of the reactive center loop sequence.
Evidence for an exosite determinant of factor Xa specificity in
heparin-activated antithrombin. Chuang, Y.-J., Swanson R, Raja
SM, Olson ST., J Biol Chem 2001 May 4;276 (18):P14961-14971.
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