Jie Zheng, Ph.D.
4145 Tupper Hall
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.
2016 Yang, F., S. Vu, V. Yarov-Yarovoy, and J. Zheng (2016) Rational design and validation of a vanilloid-sensitive TRPV2 ion channel, Proceedings of the National Academy of Sciences, USA, (in press; available online)
2015 Simonov, A.N., J.K. Holien, J.C.I. Yeung, A.D. Nguyen, C.J. Corbin, J. Zheng, V.L. Kuznetsov, R.J. Auchus, A.J. Conley, A.M. Bond, M.W. Parker, R.J. Rodgers, L.L. Martin (2015) Mechanistic scrutiny identifies a kinetic role for cytochrome b5 regulation of human cytochrome P450c17, PLoS One, 10(11): e0141252
2015 Yang, S., F. Yang, N. Wei, J. Hong, B. Li, L. Luo, M. Rong, V. Yarov-Yarovoy, J. Zheng¶, K.W. Wang¶, R. Lai¶ (2015) A pain-inducing centipede toxin targets the heat activation machinery of nociceptor TRPV1, Nature Communication, 6:8297 (¶ corresponding authors)
2015 Lee, B.H., and J. Zheng (2015) Proton block of proton-activated TRPV1 current, Journal of General Physiology, 146(2):147-159
2015 Yang, F., X. Xiao, W. Cheng, W. Yang, P. Yu, Z. Song, V. Yarov-Yarovoy, J. Zheng (2015), Structural mechanism underlying capsaicin binding and activation of nociceptive TRPV1 ion channel, Nature Chemical Biology, 11:518–524.
2015 Jie Zheng and Matthew C. Trudeau (editors), Handbook of Ion Channels, CRC Press.
** Review by Richard Aldrich (2015) A new standard: a review of Handbook of Ion Channels, Journal of General Physiology, 146(2):119-121a,
** Review by David R. Harder (2015) Physiologist, 58(4):205-208
** Review by Bingcai Guan, Zuan Zhou, Hailin Zhang (2015) Acta Physiologica Sinica, 67(5)
2015 Clifton, H.L., B. Inceoglu, L. Ma, J. Zheng, S. Schaefer (2015) TRPV1 Channels are Involved in Niacin-induced Cutaneous Vasodilation in Mice, Journal of Cardiovascular Pharmacology, 65(2):184-191
2015 Ma, L., B.H. Lee, H. Clifton, S. Schaefer, and Jie Zheng (2015) Nicotinic acid is a common regulator of heat-sensing TRPV1-4 ion channels, Scientific Reports, 5:8906; DOI:10.1038/srep08906
2015 Zheng, J., X. Zeng, and S. Wang (2015) Calcium as cellular messenger, Science China Life Sciences, 58(1):1-5
2014 Zheng, J. and L. Ma (2014) Structure and Function of the ThermoTRP Channel Pore, in L. D. Islas, & F. Qin (Eds.), Thermal Sensors, 233-257
2014 Tang, Y.Q., J.H. Zhou, F. Yang, J. Zheng, and K.W. Wang (2014) The tetramerization domain potentiates Kv4 channel function by suppressing closed-state inactivation, Biophysical Journal, 107: 1090-1104
2014 Yang, F., and J. Zheng (2014) High temperature sensitivity is intrinsic to voltage-gated potassium channels, eLife, e03255
2014 Ma, L., B.H. Lee, R. Mao, A. Cai, Y. Jia, H. Clifton, S. Schaefer, L. Xu, and J. Zheng (2014) Nicotinic acid activates the capsaicin receptor TRPV1 - a potential mechanism for cutaneous flushing, Arteriosclerosis, Thrombosis, and Vascular Biology, 34:1273-1280 ** Editorial Highlight by Dr. Stefan Offermanns (2014) ATVB 34:1122-1123.
2014 Ma, L., F. Yang, and J. Zheng. Application of fluorescence resonance energy transfer in studies of biomolecules, Journal of Molecular Structure, 1077:87-100
2014 Yang, F., L. Ma, X. Cao, K.W. Wang, and J. Zheng. Divalent cations activate TRPV1 through promoting conformational change of the extracellular region, Journal of General Physiology, 143(1): 91-103
2014 Cao, X., F. Yang, L. Ma, K.W. Wang, and J. Zheng. Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold, Journal of General Physiology, 143(1): 75-90
2013 Zheng, J. Domain-domain interactions in ion channel, Journal of General Physiology, 142(4):347-350.
2013 Lei, L., X. Cao, F. Yang, D.-J. Shi, Y.-Q. Tang, J. Zheng¶ and K.W. Wang¶. A TRPV4 Channel C-Terminal Segment Plays a Critical Role in Protein Folding and Trafficking, Journal of Biological Chemistry, 288: 10427-10439 (¶ corresponding authors)
2013 Zheng, J. and F. Yang. Patch fluorometry (version 2), in: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester
2013 Zheng, J. Molecular mechanism of TRP channels, Comprehensive Physiology, 3:221-242
2012 Jin, B., H. Wulff, J. Widdicombe, J. Zheng, D. Bers, and J. Puglisi. A Simple Device to Illustrate the Einthoven Triangle, Advances in Physiology Education, 36:319-324
2012 Cheng, W., J. Liu, C. Sun, and J. Zheng. Temperature-Sensitive TRP Ion Channels as Drug Targets for Neuropathic Pain, Progress in Physiological Sciences, 43(2): 125-130
2012 Cao, X., F. Yang, J. Zheng¶, and K.W. Wang¶. 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)
2012 Cui, Y., F. Yang, X. Cao, V. Yarov-Yarovoy, K.W. Wang, J. Zheng. 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
2012 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. Heteromeric Heat-Sensitive TRP Channels Exhibit Distinct Temperature and Chemical Response, Journal of Biological Chemistry, 287(10): 7279-7288
2011 Zhang, F., S. Liu, F. Yang, J. Zheng, K.W. Wang. 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)
2011 Ma, L., G.Y. Rychkov, E.A. Bykova, J. Zheng, and A.H. Bretag. Lateral displacement of hCLC-1 carboxyl termini during common gating and limits on their cytoplasmic location, Biochemical Journal, 436:415-428
2011 Yang, F., and J. Zheng. Fluorescence microscopy in thermoTRP channel research, in: TRP Channels, CRC Press, Taylor & Francis Group: Boca Raton
2011 Dong, B., W. Cheng, W. Li, D. Wu, J. Zheng, F. Matsumura, C.F.A. Vogel. FRET analysis of protein tyrosine kinase c-Src activation mediated via aryl hydrocarbon receptor, Biochimica et Biophysica Acta, 1810:427-451
2010 Cheng, W., C. Sun, and J. Zheng. Heteromerization of TRP channel subunits: Extending functional diversity, Protein & Cell, 1(9):802-810
2010 Yang, F., Y. Cui, K.W. Wang, and J. Zheng. 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
2009 Praporski, S., S.M. Ng, A.D. Nguyen, C. Corbin, A. Mechler, J. Zheng, A. Conley, and L. Martin. Organization of enzymes involved in sex steroid synthesis: protein-protein interactions in lipid membranes, Journal of Biological Chemistry, 284:33224-33232.
2009 Qiu, S., X.-M. Zhang, J.-Y. Cao, W. Yang, Y.-G. Yan, L. Shan, J. Zheng, and J.-H. Luo. An ER retention signal located in the extracellular amino-terminal domain of NR2A subunit of NMDA receptors, Journal of Biological Chemistry, 284:20285-20298
2009 Qu, Z., W. Cheng, Y. Cui, Y. Cui, and J. Zheng. Human disease-causing mutations disrupt an N-C terminal interaction and channel function of bestrophin 1, Journal of Biological Chemistry, 284:16473-16481.
2009 Sun, P., J. Wang, W. Gu, W. Cheng, G.-Z. Jin, E. Friedman, J. Zheng, and X. Zhen. PSD-95 regulates D1 dopamine receptor resensitization, but not receptor-mediated Gs-protein activation, Cell Research, 19:612-624.
2009 Liang, S.-S., F. Yang, C. Zhou, Y. Wang, S. Li, C.K. Sun, J.L. Puglisi, D. Bers, C. Sun, and J. Zheng. Temperature-dependent activation of neurons by continuous near-infrared laser, Cell Biochemistry and Biophysics, 53(1), 33-42.
2009 Zheng, J., and K. Matulef. Cyclic nucleotide-gated ion channels, In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester.
2009 Zheng, J. FRET and its biological application as a molecular ruler, in Handbook of Modern Biophysics, Vol. 3: Biomedical Applications in Biophysics, Humana Press.
2009 Bykova, E.A. and J. Zheng. Spectra FRET, a fluorescence resonance energy transfer method in live cells, Annual Reviews in Fluorescence 2007, Chapter 4, Springer.
2008 Zheng, J. Patch fluorometry, In: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester.
2008 Chen, T.Y., Y.F. Lin, and J. Zheng. Electrophysiological measurements of membrane proteins, in Handbook on Biophysics, Vol. 1, Chapter 5, Humana Press.
2008 Vetter, I., W. Cheng, M. Peiris, B.D. Wyse, S.J. Roberts-Thomson, J. Zheng, G.R. Monteith, P.J. Cabot. Rapid, opioid-sensitive mechanisms involved in transient receptor potential vanilloid 1 sensitization, Journal of Biological Chemistry, 283, 19540-19550.
2007 Ying, G., S.S. Liu, S. Qiu, W. Cheng, J. Zheng, J.H. Luo. Fluorescence resonance energy transfer analysis of subunit assembly of the ASIC channel, Biochemical and Biophysical Research Communications, 359, 143-150.
2007 Cheng, W., F. Yang, C.L. Takanishi, and J. Zheng. 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.
2006 Zheng, J. Patch fluorometry: shedding new light on ion channels, Physiology, 21, 6-12.
2006 Cheng, W., and J. Zheng. Applying fluorescence resonance energy transfer (FRET) techniques in live cells studies, Trends in Neurosciences [Chinese], 4, 562-570.
2006 Zheng, J. Spectroscopy-based quantitative fluorescence resonance energy transfer analysis, Methods in Molecular Biology, 337, 65-78.
2006 Bykova, E.A., X.D. Zhang, T.Y. Chen, and J. Zheng. Large movement in the C terminus of CLC-0 chloride channel during slow gating, Nature Structural and Molecular Biology, 13, 1115-1119.
2006 Takanishi, C.L., E.A. Bykova, W. Cheng, and J. Zheng. Quantification of GFP-based FRET in live cells, Brain Research, 1091(1), 132-139.
2004 Zheng, J. and W.N. Zagotta. Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels, Neuron, 42, 411-421.
- The Grass Foundation Traveling Scientist Award. 2009
- 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
- American Heart Association
- National Institute of Health
- Health System Research Award