Jie Zheng

Jie Zheng

Position Title

Department of Physiology and Membrane Biology, School of Medicine

4145 Tupper Hall

Research Interests

Ion channel gating mechanisms

Ion channels are membrane proteins that facilitate ion flux into or out of the cell or its organelles. They play critical roles in fundamental cellular functions such as neuronal signaling, muscle contraction, secretion, and fertilization. The long term goal of my research is to understand molecular mechanisms for opening (and closing) the ion permeation pathway in channels, and how this process is controlled by various physical and chemical stimuli. Malfunctions of ion channel activation due to genetic and pathological factors can lead to numerous human diseases, such as long QT syndrome, cystic fibrosis, epilepsy, schizophrenia and deficiency in learning and memory. Current research in my lab focuses on heat activation of some TRP channels that serve as biosensors for ambient temperature as well as noxious (painful) stimuli. We use multidisciplinary approaches to investigate the structural basis, functional properties, physiology as well as pathology of the highly temperature-dependent activation process.

Grad Group Affiliations

  • Molecular, Cellular and Integrative Physiology
  • Pharmacology and Toxicology

Specialties / Focus

  • Molecular Physiology


  • MCP 210A Advanced Physiology, Fall
  • HPH 400 Physiology, Fall
  • PTX 202 Principles of Pharmacology and Toxicology, Winter


  • Current Members:
    • Simon Vu (graduate student)
    • **postdoc/graduate student positions currently available
  • Previous lab members:
    • Chris Takanishi, PhD (UCD)
    • Katya Bykova, PhD ( Senior Scientist, SystImmune, Seattle, WA )
    • Wei Cheng, PhD (Associate Professor, Dalian University of Technology)
    • Ping Liang, PhD (Professor, Zhejiang University)
    • Yuanyuan Cui, PhD (Research Assistant Professor, Washington State University, Pullman )
    • Xu Cao, PhD (Postdoc., NIH)
    • Linlin Ma, PhD ( Faculty, Flinders University, Adelaide, Australia )
    • Yuan Zhao (Graduate Student, Yale)
    • Wei Yang, PhD (Professor and Vice Dean, Zhejiang University)
    • Shilong Yang, PhD (Investigator, Chinese Academy of Sciences, Kunming Zoology Institute)
    • Xian Xiao, PhD (Faculty, Westlake University)
    • Bo Hyun Lee, PhD (Postdoc., University of Washington, Seattle, WA)
    • Fan Yang, PhD (Professor, Zhejiang University)

Honors and Awards

  • Guanghua Scholarship, Beijing University, 1988
  • University Scholarship, Yale University, 1992-1995
  • Research Associate, Howard Hughes Medical Institute, 2000-2003
  • UCD Health System Research Award, 2008-2009
  • the Grass Foundation Travelling Scientist Award, 2009
  • Jewish National Fund Faculty Fellowship Award, 2018

    Professional Societies

    • Society for Neuroscience
    • Biophysical Society
    • Society of General Physiology
    • American Physiological Society
    • Chinese Neuroscience Society


    • 1998 PhD Physiology Yale University
    • 1991 MS Biophysics Peking University
    • 1988 BS Physiology and Biophysics Peking University


    Dong, Y., Y. Yin, S. Vu, F. Yang, V. Yarov-Yarovoy, Y. Tian, J. Zheng (2019) A distinct structural mechanism underlies TRPV1 activation by piperine, BBRC, (in press)

    Yin, Y., Y. Dong, S. Vu, F. Yang, V. Yarov-Yarovoy, Y. Tian, J. Zheng (2019) Structural Mechanism Underlying TRPV1 Activation by Pungent Compounds in Gingers, British Journal of Pharmacology, (in press)

    Luo, L., Y. Wang, B. Li, L. Xu, P.M. Kamau, J. Zheng¶, F. Yang¶, S. Yang¶, R. Lai¶ (2019) Molecular Basis for Heat Desensitization of TRPV1 Ion Channels, Nature Communications, 10:2134 (¶ corresponding authors)

    Wang, H., Z. Xu, B.H. Lee, S. Vu, L. Hu, M. Lee, D. Bu, X. Cao, S. Hwang, Y. Yang, J. Zheng¶, Z. Lin¶ (2019) Gain-of-function mutations in TRPM4 activation gate cause progressive symmetric erythrokeratoderma, Journal of Investigative Dermatology, 139:1089-1097 (¶ corresponding authors)

    Yang, F., X. Xiao, B.H. Lee, S. Vu, W. Yang, V. Yarov-Yarovoy, J. Zheng (2018) The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel, Nature Communications, 9:2879 | DOI: 10.1038/s41467-018-05339-6

    Han, Y., B. Li, T. Yin, C. Xu, R. Ombati, L. Luo, Y. Xia, L. Xu, J. Zheng, Y. Zhang, F. Yang, G. Wang, S. Yang, R. Lai (2018) Molecular mechanism of tree shrew’s insensitivity to pungency, PLoS Biology, 16(7): e2004921.

    Yang, S., F. Yang, B. Zhang, B.H. Lee, B. Li, L. Luo, J. Zheng¶, and R. Lai¶ (2017) A novel bi-modal activation mechanism underlies scorpion toxin induced pain, Science Advances, 3: e1700810 (¶ corresponding authors)

    • Highlighted by Discover Magazine

    Yang, F., and J. Zheng (2017) Understand spiciness: mechanism of TRPV1 channel activation by capsaicin, Protein & Cell, 8(3):169-177

    He, X. C. Shen, Q. Lu, J. Li, Y. Wei, L. He, R. Bai, J. Zheng, N. Luan, Z. Zhang, M. Rong, R. Lai (2016) Prokineticin 2 Plays a Pivotal Role in Psoriasis, EBioMedicine,  DOI: 10.1016/j.ebiom.2016.10.022

    Ma, L., F. Yang, S. Vu, and J. Zheng (2016) Exploring functional roles of TRPV1 intracellular domains with unstructured peptide-insertion screening, Scientific Reports, 6:33827, DOI: 10.1038/srep33827

    Kim, S., D. Barry, X.Y. Liu, S. Yin, A. Munanairi, Q.T. Meng, W. Cheng, P. Mo, L. Wan, S.B. Liu, K. Ratnayake, Z. Q. Zhao, N. Gautam, J. Zheng, W.K.A. Karunarathne, and Z. F. Chen (2016) Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations, Science Signaling, 9(437): ra71

    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, E3657–E3666

    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

    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)

    Lee, B.H. and J. Zheng (2015), Proton Block of Proton-Activated TRPV1 Current, Journal of General Physiology, 146(2):147-159

    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

    Jie Zheng and Matthew C. Trudeau (editors), Handbook of Ion Channels, CRC Press, 2015

    ** Review by Richard Aldrich (2015) A new standard: a review of Handbook of Ion Channels, Journal of General Physiology, 146(2):119-121

    ** Review by David R. Harder (2015) Physiologist, 58(4):205-208

    ** Review by Bingcai Guan, Zuan Zhou, Hailin Zhang (2015) Handbook of Ion Channels——一部系统介绍离子通道的新作问世, Acta Physiologica Sinica, 67(5)

    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

    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

    Zheng, J., X. Zeng, and S. Wang (2015) Calcium as cellular messenger, Science China Life Sciences, 58(1):1-5

    Zheng, J. and L. Ma (2014) Structure and Function of the ThermoTRP Channel Pore, Current Topics in Membranes, 74:233-257

    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 

    Yang, F., and J. Zheng (2014) High temperature sensitivity is intrinsic to voltage-gated potassium channels, eLife, e03255

    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, 34:1272-1280

    ·       Editorial highlight by Dr. Stefan Offermanns (2014) ATVB 34:1122-1123

    Ma, L., F. Yang, and J. Zheng (2014) Application of fluorescence resonance energy transfer in studies of biomolecules, Journal of Molecular Structure, 1077:87-100

    Yang, F., L. Ma, X. Cao, K.W. Wang, and J. Zheng (2014) Divalent cations activate TRPV1 through promoting conformational change of the extracellular region, Journal of General Physiology, 143(1): 91-103

    Cao, X., F. Yang, L. Ma, K.W. Wang, and J. Zheng (2014) Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold, Journal of General Physiology, 143(1): 75-90

    Zheng, J. (2013) Domain-domain interactions in ion channel, Journal of General Physiology, 142(4): 347-350

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

    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 288: 10427-10439 (¶ corresponding authors)

    Zheng, J. and F. Yang (2013) Patch fluorometry (version 2), in: Encyclopedia of Life Sciences (ELS), John Wiley & Sons, Ltd: Chichester 

    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: M.X. Zhu (Ed.) 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

    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, USA, 107:7083-7088

    ·       Highlighted in Cell (2010)141:377 and Faculty 1000 Biology

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

    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

    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

    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

    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

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

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

    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

    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

    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 T. Jue (Ed.) Handbook of Biophysics, Vol. 1: Fundamental Concepts in Biophysics, Chapter 5, Humana Press

    Gao, Y., 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

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

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

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

    Zheng, J., and W.N. Zagotta (2003) Patch-clamp fluorometry recording of conformational rearrangements of ion channels, Science’s STKE, pl7

    Zheng, J., M.D. Varnum, and W.N. Zagotta (2003) Disruption of an intersubunit interaction underlies Ca2+-calmodulin modulation of cyclic nucleotide-gated channels, Journal of Neuroscience, 23(22): 8167-8175

    Zheng, J., M.C. Trudeau, and W.N. Zagotta (2002) Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit, Neuron, 36: 891-896

    ·       Commentary in Nature Review Neuroscience 4(1):10

    ·       Commentary in Neuron 36: 997-999

    Zheng, J., L. Venkataramanan, and F.J. Sigworth (2001) Hidden Markov model analysis of intermediate gating steps associated with the pore gate of Shaker potassium channels, Journal of General Physiology, 118: 547-562

    Zheng, J., and W.N. Zagotta (2000) Gating rearrangements in cyclic nucleotide-gated channels revealed by patch-clamp fluorometry, Neuron, 28: 369-374

    Zheng, J., and F.J. Sigworth (1998) Intermediate conductances during deactivation of heteromultimeric Shaker potassium channels, Journal of General Physiology, 112: 457-474

    Zheng, J., and F.J. Sigworth (1997) Selectivity changes during activation of mutant Shaker potassium channels, Journal of General Physiology, 110: 101-117 

    ·       Featured on the cover

    Mathur, R., J. Zheng, Y. Yan, and F.J. Sigworth (1997) Role of the S3-S4 linker in Shaker potassium channel activation, Journal of General Physiology, 109: 191-200

    Zhang, R.J., D.J. Zou, and J. Zheng (1995) Correlation of receptive field position of mechanosensory neurons and the strength of their connections to AP neurons in the CNS of the leech (Whitmania pigra), Invertebrate Neuroscience, 1: 249-254

    Zhang, R.J., D.J. Zou, J. Zheng, and W.H. Xiong (1992) Positional discrimination of the AP neuron synapses in the leech Whitmania pigra, Science in China, Series B, 12: 1287-1294

    Liu, K.Q., J. Zheng, Y.Q. Lu, Y.H. Zhang, and F. Liu (1991) Automatic analysis of single-channel records, Acta Biophysica Sinica, 7(3): 346-351