Jie Zheng, Ph.D.
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.
Graduate Group Affiliations
An updated list of current publications: Google Scholar
Zhao, F., S. Wang, Y. Li, J. Wang, Y. Wang, C. Zhang, Y. Li, L. Huang, Y. Yu, B. Yu, J. Zheng, I. Pessah, Z. Cao (2021) Surfactant cocamide monoethanolamide causes eye irritation by activating nociceptor TRPV1, British Journal of Pharmacology, (in press)
Liu, C., R. Reese, S. Vu, L. Rougé, S. Shields, H. Chen, Y. Shi, T. Chernov-Rogan, K. Johnson, D.M.Z. Greiner, P.B. Kohli, D. Hackos, S. Kakiuchi-Kiyota, B. Brillantes, C. Tam, T. Li, J. Wang, S. Magnuson, M. Volgraf, J. Payandeh, J. Zheng, A. Rohou and J. Chen (2021) A non-covalent ligand reveals biased agonism at the TRPA1 ion channel, Neuron, 109(2):273-284.e4. doi: 10.1016/j.neuron.2020.10.014.
Vu, S., V. Singh, H. Wulff, V. Yarov-Yarovoy, J. Zheng (2020) New capsaicin analogs as molecular rulers to define the permissive conformation of the mouse TRPV1 ligand-binding pocket, eLife, 9:e62039. DOI: https://doi.org/10.7554/eLife.62039
Yang, F.¶, L. Xu, B.H. Lee, X. Xiao, V. Yarov-Yarovoy, J. Zheng¶ (2020) An unorthodox mechanism underlying voltage sensitivity of TRPV1 ion channel, Advanced Science, 2000575. DOI: 10.1002/advs.202000575
Du, G., Y. Tian, Z. Yao, S. Vu, J. Zheng, L. Chai, K. Wang, S. Yang (2020) A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds, Journal of Biological Chemistry, 295(28):9641-9649; DOI: 10.1074/jbc.RA120.013037
Zhu, A., A. Aierken, Z. Yao, S. Vu, Y. Tian¶, J. Zheng¶, S. Yang¶, F. Yang¶ (2020) A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel, Toxicon, 178:41-49; DOI:10.1016/j.toxicon.2020.02.016
Yao, Z., P.M. Kamau, Y. Han, J. Hu, A. Luo, L. Luo¶, J. Zheng¶, Y. Tian¶, R. Lai¶ (2019) The Latoia consocia caterpillar induces pain by targeting nociceptive ion channel TRPV1, Toxins, 11: 695; DOI:10.3390/toxins11120695
6. 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, Biochemical and Biophysical Research Communications, 516: 365-372 DOI: 10.1016/j.bbrc.2019.06.039
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, 176: 3364–3377. DOI: 10.1111/bph.14766
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¶ (2018) 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)
*** The paper by Yang, S., F. Yang, et al.(2017) is 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), (2015) 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)
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, in L. D. Islas, & F. Qin (Eds.), Thermal Sensors, 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, 34:1273-1280 ** 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.
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
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.
- 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
- The Grass Foundation Traveling Scientist Award. 2009