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  Wenji Dong, Ph.D.

Assistant Professor

McCoy South S203E

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

Brouillette, C. G., Dong, W. J., Yang, Z. W., Ray, M. J., Protasevich, II, Cheung, H. C., and Engler, J. A. (2005) Forster resonance energy transfer measurements are consistent with a helical bundle model for lipid-free apolipoprotein A-I. Biochemistry 44, 16413-25.

Robinson JM. Dong WJ. Xing J. Cheung HC. Switching of Troponin I: Ca2+ and Myosin Induced Activation of the Heart. Journal of Molecular Biolog. 340 295-305, 2004.

Kobayashi T. Dong, WJ. Burkart EM. Cheung HC. 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.

Dong WJ. Robinson JM. Xing J. Cheung HC. FRET-sensed kinetics of conformational transitions in cardiac troponin induced by Ca2+ dissociation. Journal of Biological Chemistry. 278 42394-402, 2003.

Dong WJ. Robinson JM. Stagg S. Xing J. Cheung HC. Ca2+-induced conformational transition in the inhibitory and regulatory regions of cardiac troponin I. Journal of Biological Chemistry. 278 8686-92, 2003

Sheldahl C. Xing J. Dong WJ. Harvey SC. Cheung HC. The Calcium-Saturated cTnI/cTnC Complex: Structure of the Inhibitory Region of cTnI. Biophysical Journal. 84 1057-64, 2003.

Robinson JM. Dong WJ. Cheung HC. 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

Burghardt TP. Park S. Dong WJ. Xing J. Cheung HC. Ajtai K. Energy transduction optical sensor in skeletal myosin. Biochemistry. 42 5877-84, 2003

Heller WT, Finley NL, Dong WJ, Timmins P, Cheung HC, Rosevear PR, Trewhella J.  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.

Wen-Ji Dong, Jun Xing, John R. Robinson and Herbert C. Cheung. Ca2+ Induced An Extended Conformation of the Inhibitory Region of Troponin I in Cardiac Muscle Troponin. Journal of Molecular Biology. 314,51-61, 2001.

M. Bret Abbott, Wen-Ji Dong, Alex Dvoresky, Beverly DaGrue, Richard Caprioli, Herbert C. Cheung and Paul R. Rosevear. Modulation of Cardiac Troponin C-Cardiac Troponin I Regulatory Interactions By N-terminus of Cardiac Troponin I. Biochemistry. 40 5992-6001, 2001.

 

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