The Gene and Linda Voiland School of

Chemical Engineering and Bioengineering

Faculty

Wenji Dong, Ph.D.

Assistant Professor

The Gene and Linda Voiland
School of Chemical Engineering and Bioengineering
Washington State University
118 Dana Hall Spokane St.
P.O. Box 642710
Pullman, WA 99164-2710



Office: McCoy North 207(Tel: 509 335-5798)
Lab: McCoy North 201(Tel: 509 335-5937)
wdong@vetmed.wsu.edu

Adjunct Faculty member of VCAPP

http://www.vetmed.wsu.edu/research_vcapp/dong_w.asp

Graduate Students

Yanling Qiao
Daniel Rieck
Zhiqun Zhang

Research Interests

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

Dr. Dong 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 the Gene and Linda Voiland School of Chemical Engineering and Bioengineering in 2006.

Selected Publications

(click on most recent titles for link to full articles)

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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.
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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

The Gene & Linda Voiland School of Chemical Engineering and Bioengineering, PO Box 642710, Washington State University, Pullman WA 99164-2710, 509-335-4332, Email ChEBE: chebe AT wsu DOT edu