Wenji Dong, Ph.D.
Assistant Professor (Bioengineering)
McCoy North 207
E-Mail: wdong@vetmed.wsu.edu
Phone: (509) 335-5798
Research in my lab is multi-disciplinary, involving cardiac muscle
biology and mechanics, protein chemistry and engineering, fluorescence
techniques, computer modeling, nanoscale biosensor design and
engineering. Our long-term research objective has two components. The
first component focuses on the understanding of the Ca2+ switching
mechanism of cardiac myofilament in healthy and diseased hearts.
Cardiac muscle contraction is initiated by Ca2+ binding to cardiac
troponin C triggering a series of functional structural changes within
the thin filament. These serious structural transitions are regulated by
both Ca2+ binding and cross-bridge cycling, and modulated by protein
phosphorylation and cardiomyopathy mutations.
A full understanding of these mechanisms is critical for research
efforts to prevent, diagnose, and treat myocardial diseases. This
requires detailed functional, structural, thermodynamic, and kinetic
knowledge of thin filament activation transitions with respect to Ca2+
activation. Cardiac thin filament is a highly organized and complex
system, and each regulatory unit contains more than ten different
proteins. Because of complexity and size of the system, most
conventional structural biology technologies such as x-ray
crystallography and NMR fail in providing structural and kinetic
information. We believe fluorescence resonance energy transfer (FRET)
is an alternative approach to fill the gap. The outcomes of this study
will enable us to design a fluorescence assay to screen drug candidates
of Ca2+ sensitizer, a promising therapeutic drug for treatment of heart
failure. The second component involves nanoscale sensor and probe
deigns for protein identifications, such as the detection of cardiac
biomarkers, which are indicators of heart attack. These designs will use
fluorescence resonance energy transfer technique as signal sensing tool
combining with nanoparticle engineering (gold colloid particles, polymer
particles and vesicle structure particles), molecular biology
techniques, and chemical and biological processes. As a part of this
research, depending on the research areas, students will be exposed to
the cardiovascular system, protein biochemistry and molecular biology,
design and fabricate nanoparticles and vesicle particles and modify
these particles with fluorescent probes, learn and apply fluorescence
spectroscopy techniques to sensor construction, develop assay for drug
screening, and perform computer modeling for cardiac myofilament
activation and deactivation.
Biographical Information
Wenji Dong, Assistant Professor, received a B.S. in chemistry in
1982, a M.S. in inorganic chemistry in 1985 from Lanzhou University, P.
R. China. He received a scholarship from British Council of United
Kingdom for studies at the University of London, England and obtained a
Ph.D. in physical chemistry in 1992. From 1993-1994 he was a
postdoctoral fellow at Department of Chemistry of University of Western
Ontario, Canada. He moved to the University of Alabama at Birmingham
where he was a Research Fellow of the Muscular Dystrophy Association
from 1994 -1996, a Research Instructor from 1996-2001, and a Research
Assistant Professor from 2001- 2005. He joined the faculty of Washington
State University as an assistant professor in the department of VCAPP
and School of Chemical Engineering and Bioengineering in 2006.
Selected Publications (click on most recent titles for link to full
articles)
Xing, J., Jayasundar J. J., Ouyang, Y. and Dong, W-J.
(2009),
FRET structural kinetics studies of cardiac thin filament deactivation,
Journal of Biology Chemistry 284, 16432-16441
Xing, J. Chinnaraj, M., Zhang, Z. Cheung, H. C. and Dong, W-J.(2008)
Structural studies of interactions between cardiac troponin I and actin
in regulated thin filament using Frster resonance energy transfer,
Biochemistry, 47, 13383-13393
Robinson J.M., Cheung H.C., and Dong W-J.
The cardiac Ca2+-sensitive regulatory switch, a system in dynamic
equilibrium, Biophysical Journal, 95(10): 4772-4789, 2008
Dong, W-J., Ouyang, Y., Xing, J., An, J., and
Cheung, H. C.
Structural kinetics of cardiac troponin C mutants linked to familial
hypertrophic and dilated cardiomyopathy in troponin complexes. J
Biol Chem, 283 (6), 34243432, 2008
Wen-Ji Dong, Jayasundar J. J., An, J., Xing, J. and
Cheung, H. C. (2007)
Effects of PKA phosphorylation of cardiac troponin I and strong
crossbridge on conformational transitions of the N-domain of cardiac
troponin C in regulated thin filaments. Biochemistry, 46(34),
9752-9761
Wen-Ji Dong, Jianli An, Jun Xing and Herbert C
Cheung. (2006)
Structural transition of the inhibitory region of troponin I within the
regulated cardiac thin filament. Archive of Biochemistry and
Biophysics 456(2) pp 135-142
Christie G. Brouillette, Wen-Ji Dong, Zhengrong W.
Yang, Marjorie J. Ray, Irina I Protasevich, Herbert C Cheung, and
Jeffery A. Engler, (2005) Forster resonance energy transfer measurements
are consistent with a helical bundle model for lipid-free apolipoprotein
A-I. Biochemistry 44, 16413-25
John M. Robinson, Wen-Ji Dong, Jun Xing, Herbert C
Cheung. Switching of Troponin I: Ca2+ and Myosin Induced Activation of
the Heart. Journal of Molecular Biology. 340 295-305, 2004.
Tomoyoshi Kobayashi, Wen-Ji Dong, Eileen M. Burkart,
Herbert C Cheung, Solaro RJ. Effects of Protein Kinase C Dependent
Phosphorylation and a Familial Hypertrophic Cardiomyopathy-Related
Mutation of Cardiac Troponin I on Structural Transition of Troponin C
and Myofilament Activation. Biochemistry. 43 5996-6004, 2004
Wen-Ji Dong, John M. Robinson, Jun Xing and Herbert
C Cheung. FRET-sensed kinetics of conformational transitions in cardiac
troponin induced by Ca2+ dissociation. Journal of Biological Chemistry.
278, 42394-402, 2003
Wen-Ji Dong, John M. Robinson, S. Stagg, Jun Xing
and Herbert C Cheung. Ca2+-induced conformational transition in the
inhibitory and regulatory regions of cardiac troponin I. Journal of
Biological Chemistry. 278 8686-92, 2003
Christopher Sheldahl. Jun Xing, Wen-Ji Dong, Stephen
C. Harvey and Herbert C Cheung. The Calcium-Saturated cTnI/cTnC Complex:
Structure of the Inhibitory Region of cTnI. Biophysical Journal. 84,
1057-64, 2003
John M. Robinson, Wen-Ji Dong, Herbert C Cheung. Can
Forster resonance energy transfer measurements uniquely position
troponin residues on the actin filament? A case study in
multiple-acceptor FRET. Journal of Molecular Biology. 329, 371-80, 2003
Thomas P Burghardt, Sungjo Park, Wen-Ji Dong, Jun
Xing, Herbert C Cheung, and Katalin Ajtai Energy transduction optical
sensor in skeletal myosin. Biochemistry. 42, 5877-84, 2003
William T. Heller, Natosha L. Finley, Wen-Ji Dong,
Peter Timmins, Herbert C. Cheung, Paul R. Rosevear, and Jill Trewhella.
Small-angle neutron scattering with contrast variation reveals spatial
relationships between the three subunits in the ternary cardiac troponin
complex and the effects of troponin I phosphorylation. Biochemistry. 42,
7790-800, 2003
PubMed Publications (Note: Search for other links to publications
may produce additional "WJ Dong" authors)
