Recent/Current
Research Funding

American Heart
Association

National Institute
of Health

Health System
Research Award

Graduate Group Affiliations

Molecular, Cellular and
Integrative Physiology

Pharmacology and
Toxicology Graduate

Research Interests

For more information, visit the Jie Zheng Laboratory website.

Molecular mechanisms of ion channel function. Using novel fluorescence techniques in the combination with electrophysiology, molecular biology, and biochemistry to better understand ion channel structure and its dynamic rearrangements the underlie channel function in cellular signal transduction.

Ion channels form the basis of electrical excitability of neurons and muscle cells. In response to specific electrical or chemical stimuli, these membrane proteins open a pathway across the cell membrane for selected ions, causing changes in membrane potential or intracellular levels of calcium. Activation of an ion channel is under extremely precise control that allows highly specialized processes, e.g., photoreceptor cells to detect the presence of a single photon. Research in my laboratory focuses on the protein structures critical for channel organization, activation, and modulation. The moving parts of the channel are labeled with fluorophores that serve as a molecular sensor for local conformational rearrangements. Recording the fluorescence emission let us directly observe channel structural changes in real time under physiological conditions. The same population of channels is simultaneously monitored with patch-clamp recordings so that we can correlate structure changes to the channel's function states. In particular, we use Fluorescence Resonance Energy Transfer (FRET) to measure atomic distances between channel structures.

 

Representative Publications

Lei, L., X. Cao, F. Yang, D.-J. Shi, Y.-Q. Tang, J. Zheng¶ and K.W. Wang¶ (2013) A TRPV4 Channel C-Terminal Segment Plays a Critical Role in Protein Folding and Trafficking, Journal of Biological Chemistry (in press) (¶ corresponding authors)

Zheng, J. (2013) Molecular mechanism of TRP channels, Comprehensive Physiology, 3:221-242

Jin, B., H. Wulff, J. Widdicombe, J. Zheng, D. Bers, and J. Puglisi (2012) A Simple Device to Illustrate the Einthoven Triangle, Advances in Physiology Education, 36:319-324

Cheng, W., J. Liu, C. Sun, and J. Zheng (2012) Temperature-Sensitive TRP Ion Channels as Drug Targets for Neuropathic Pain, Progress in Physiological Sciences, 43(2): 125-130

Cao, X., F. Yang, J. Zheng¶, and K.W. Wang¶ (2012) Intracellular proton-mediated activation of TRPV3 channels accounts for exfoliation effect of alpha hydroxyl acids on keratinocytes, Journal of Biological Chemistry, 287(31): 25905-25916   (¶ corresponding authors)

Cui, Y., F. Yang, X. Cao, V. Yarov-Yarovoy, K.W. Wang, J. Zheng (2012) Selective disruption of high-sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations, Journal of General Physiology, 139 (4)273-283. Featured on the cover

Cheng, W., F. Yang, S. Liu, C.K. Colton, C. Wang, Y. Cui, X. Cao, M.X. Zhu, C. Sun, K.W. Wang, and J. Zheng (2012) Heteromeric Heat-Sensitive TRP Channels Exhibit Distinct Temperature and Chemical Response, Journal of Biological Chemistry, 287(10): 7279-7288

Zhang, F., S. Liu, F. Yang, J. Zheng, K.W. Wang (2011) Identification of a tetrameric assembly domain in the C-terminus of heat-activated TRPV1 channels, Journal of Biological Chemistry, 286(17):15308-15316 (corresponding authors)

Ma, L., G.Y. Rychkov, E.A. Bykova, J. Zheng, and A.H. Bretag (2011) Lateral displacement of hCLC-1 carboxyl termini during common gating and limits on their cytoplasmic location, Biochemical Journal, 436:415-428

Yang, F., and J. Zheng (2011) Fluorescence microscopy in thermoTRP channel research, in: TRP Channels, CRC Press, Taylor & Francis Group: Boca Raton

Dong, B., W. Cheng, W. Li, D. Wu, J. Zheng, F. Matsumura, C.F.A. Vogel (2011) FRET analysis of protein tyrosine kinase c-Src activation mediated via aryl hydrocarbon receptor, Biochimica et Biophysica Acta, 1810:427-451

Cheng, W., C. Sun, and J. Zheng (2010) Heteromerization of TRP channel subunits: Extending functional diversity, Protein & Cell, 1(9):802-810

Yang, F., Y. Cui, K.W. Wang, and J. Zheng (2010) Thermosensitive TRP channel outer pore is part of the temperature activation pathway, Proceedings of the National Academy of Sciences, 107:7083-7088.
Highlighted in Cell (2010) 141:377 and Faculty 1000 Biology

Praporski, S., S.M. Ng, A.D. Nguyen, C. Corbin, A. Mechler, J. Zheng, A. Conley, and L. Martin (2009) Organization of enzymes involved in sex steroid synthesis: protein-protein interactions in lipid membranes, Journal of Biological Chemistry, 284:33224-33232.

Qiu, S., X.-M. Zhang, J.-Y. Cao, W. Yang, Y.-G. Yan, L. Shan, J. Zheng, and J.-H. Luo (2009) An ER retention signal located in the extracellular amino-terminal domain of NR2A subunit of NMDA receptors, Journal of Biological Chemistry, 284:20285-20298

Qu, Z., W. Cheng, Y. Cui, Y. Cui, and J. Zheng (2009) Human disease-causing mutations disrupt an N-C terminal interaction and channel function of bestrophin 1, Journal of Biological Chemistry, 284:16473-16481.

Sun, P., J. Wang, W. Gu, W. Cheng, G.-Z. Jin, E. Friedman, J. Zheng, and X. Zhen (2009) PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation, Cell Research 19:612-624.

Liang, S.-S., F. Yang, C. Zhou, Y. Wang, S. Li, C.K. Sun, J.L. Puglisi, D. Bers, C. Sun, and J. Zheng (2009) Temperature-dependent activation of neurons by continuous near-infrared laser, Cell Biochemistry and Biophysics, 53(1), 33-42.

Zheng, J., and K. Matulef (2009) Cyclic nucleotide-gated ion channels, In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester. 

Zheng, J. (2009) FRET and its biological application as a molecular ruler, in Handbook of Modern Biophysics, Vol. 3: Biomedical Applications in Biophysics, Humana Press.

Bykova, E.A. and J. Zheng (2009) Spectra FRET, a fluorescence resonance energy transfer method in live cells, Annual Reviews in Fluorescence 2007, Chapter 4, Springer.

Zheng, J. (2008) Patch fluorometry, In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester.

Chen, T.Y., Y.F. Lin, and J. Zheng (2008) Electrophysiological measurements of membrane proteins, in Handbook on Biophysics, Vol. 1, Chapter 5, Humana Press.

Vetter, I., W. Cheng, M. Peiris, B.D. Wyse, S.J. Roberts-Thomson, J. Zheng, G.R. Monteith, P.J. Cabot (2008) Rapid, opioid-sensitive mechanisms involved in transient receptor potential vanilloid 1 sensitization, Journal of Biological Chemistry, 283, 19540-19550.

Ying, G., S.S. Liu, S. Qiu, W. Cheng, J. Zheng, J.H. Luo (2007) Fluorescence resonance energy transfer analysis of subunit assembly of the ASIC channel, Biochemical and Biophysical Research Communications, 359, 143-150.

Cheng, W., F. Yang, C.L. Takanishi, and J. Zheng (2007) Thermosensitive TRPV Channel Subunits Co-assemble into Heteromeric Channels with Intermediate Conductance and Gating Properties, Journal of General Physiology, 129, 191-207.  Featured on the cover.

Zheng, J. (2006) Patch fluorometry: shedding new light on ion channels, Physiology, 21, 6-12.

Cheng, W., and J. Zheng (2006) Applying fluorescence resonance energy transfer (FRET) techniques in live cells studies, Trends in Neurosciences [Chinese], 4, 562-570.

Zheng, J. (2006) Spectroscopy-based quantitative fluorescence resonance energy transfer analysis, Methods in Molecular Biology, 337, 65-78.

Bykova, E.A., X.D. Zhang, T.Y. Chen, and J. Zheng (2006) Large movement in the C terminus of CLC-0 chloride channel during slow gating, Nature Structural and Molecular Biology, 13, 1115-1119.

Takanishi, C.L., E.A. Bykova, W. Cheng, and J. Zheng (2006) Quantification of GFP-based FRET in live cells, Brain Research, 1091(1), 132-139.

Zheng, J. and W.N. Zagotta (2004), Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels, Neuron, 42, 411-421.

 

Recent/Current Teaching

MCP210A, Advanced Physiology, Co-Instructor of Record
MCP210L, Lab Rotation, Co-Instructor of Record
PTX202, Principles of Pharmacology: Cellular and Molecular Basis of Drug Action
HPH400, Medical Human Physiology
MCP216, Neurophysiology
MCP209, Seminar on Frontiers in Neurobiology
HPH199, Special Study
HPH299, Research
MCP-BPH241, Membrane Biology
BPH200B, Techniques in Biophysics

 

Honors and Awards

• The Grass Foundation Traveling Scientist Award. 2009