Education

Postdoctoral Fellow
State University of New York, 1999
Ph.D.
Peking University Health Science Center, China, 1998

Areas of Interest

Research Interests

TRP channel function in the nervous system

Research Information

TRP channel function in the nervous system

My research focuses on investigating the function and regulation of Transient Receptor Potential (TRP) channels in the nervous system.  These novel cation channels mediate both membrane depolarization and calcium influx into cells and are thought to play important roles in sensory transduction as well as synaptic transmission.  Using whole-cell patch clamp techniques on mouse brain slices, we have developed methods to directly study TRPC4 and TRPC5 channel function in neurons of lateral septal nucleus, hippocampal subicular nucleus and lateral amygdala nucleus and TRPC3 channel function in Purkinje neurons of the cerebellar cortex. In addition, we have well-established conditions for whole-cell path clamp recording of TRPV1 and TRPA1 channel functions in dissociated dorsal root ganglia (DRG) neurons as well as postsynaptic responses to the stimulation of these channels of spinal dorsal horn neurons in spinal cord slices.

Currently, we are studying the function and regulation of TRPC4 and TRPC5 channels in the central nervous system. Unlike voltage-gated ion channels and ligand-gated channels, TRPC channels are receptor-operated channels in that their activation is dependent on stimulation of metabotropic receptors and/or growth factor receptors. We have found that stimulation of a single receptor type is often insufficient to cause full activation of TRPC4/C5 channels while costimulation of multiple receptor types, e. g. those that activate Gq/11 and Gi/o protein pathways, results in maximal channel activation.  Therefore, it appears that TRPC4/C5 can integrate signal inputs from multiple receptor types expressed in the same neuron, through which they can modulate neuronal excitability and synaptic plasticity. This integration function is dependent on the spatial and temporal patterns of the receptor stimulation.  In order to test this hypothesis, we have studied TRPC4/C5 channel activities induced by agonists which simultaneously activate multiple G protein signaling pathways.  These experiments will establish TRPC4/C5 channels as coincident detectors of multiple cell signaling pathways.  In brain slice recordings, we found that fast inhibitory neurotransmission, if combined with other stimulations, targeting at a different G protein signaling pathway and intracellular calcium concentration rise in a highly temporal pattern, can be turned into a long-lasting depolarization via TRPC4/C5-like channels.  As a result, the excitability and the strength of synaptic output of the affected neuron will change dramatically depending on the inputs it receives and whether and to what degree these inputs can trigger TRPC4/C5 channel activation.

My future research will focus on: (1) TRPC channel function in the integration of signal inputs from different brain areas, (2) signal transduction pathways involved in the activation of TRPC channels in neurons and their importance in neurotransmission, (3) molecular mechanisms of regulation of TRP channels in general and their implications in neuronal signaling.

Publications

Publication Information

REFERENCES

  • Alexander JK, Cox GM, Tian JB, Zha AM, Wei P, Kigerl KA, Reddy MK, Dagia NM, Sielecki T, Zhu MX, Satoskar AR, McTigue DM, Whitacre CC, Popovich PG. (2012). Macrophage migration inhibitory factor (MIF) is essential for inflammatory and neuropathic pain and enhances pain in response to stress. Exp Neurol, 236, 351-362.
  • Hester ME, Murtha MJ, Song S, Rao M, Miranda CJ, Meyer K, Tian J, Boulting G, Schaffer DV, Zhu MX, Pfaff SL, Gage FH, Kaspar BK. (2011). Rapid and Efficient Generation of Functional Motor Neurons From Human Pluripotent Stem Cells Using Gene Delivered Transcription Factor Codes. Mol Ther, 19, 1905-1912.
  • Miller M, Shi J, Zhu Y, Kustov M, Tian JB, Stevens A, Wu M, Xu J, Long S, Yang P, Zholos AV, Salovich JM, Weaver CD, Hopkins CR, Lindsley CW, McManus O, Li M, Zhu MX. (2011) Identification of ML204: a novel potent antagonist that selectively modulates native TRPC4/C5 channels. J Biol Chem 286(38):33436-46.
  • Hu H*, Tian JB*, Zhu Y*, Wang C, Xiao R, Herz JM, Wood JD, Zhu MX. (2010) Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs. Pflugers Arch, 459(4):579-92. (*: Equally contributed authors)
  • Hill ER, Tian JB, Tilley MR, Zhu MX, Gu HH. (2009) Potencies of Cocaine Methiodide on Major Cocaine Targets in Mice. PLoS ONE, 4(10):e7578.
  • Iscru E, Serinagaoglu Y, Schilling K, Tian JB, Bowers-Kidder SL, Zhang R, Morgan JI, Devries AC, Nelson RJ, Zhu MX, Oberdick J. (2009) Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific G(i/o) modulator, Pcp2(L7). Mol Cell Neurosci, 40(1):62-75.
  • Tian JB, King JS, Bishop GA. (2008) Stimulation of the inferior olivary complex alters the distribution of the type 1 corticotropin releasing factor receptor in the adult rat cerebellar cortex. Neuroscience, 153(1):308-17.
  • Xiao R, Tang J, Wang C, Colton CK, Tian JB, Zhu MX. (2008) Calcium plays a central role in the sensitization of TRPV3 channel to repetitive stimulations. J Biol Chem 283(10):6162-74.
  • Xiao R*, Tian JB*, Tang J, Zhu, MX. (2008) The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active. Cell Calcium, 43(4):334-43. (*: Equally contributed authors)
  • Tian JB, Shan X, Bishop GA and King JS. (2006) Presynaptic localization of a truncated isoform of the type 2 corticotropin releasing factor receptor in the Cerebellum. Neuroscience, 138(2): 691-702.
  • Tian JB† and Bishop GA. (2003) Frequency-dependent expression of corticotropin releasing factor in the rat’s cerebellum. Neuroscience, 121(2): 363-377. (†: Corresponding author)
  • Tian JB† and Bishop GA. (2002) Stimulus-dependent activation of c-Fos in neurons and glia in the rat cerebellum. Journal of Chemical Neuroanatomy, 23: 157-170. (†: Corresponding author)
  • Wu LZ, Cui CL, Tian JB, Ji D, Han JS. (1999) Suppression of morphine withdrawal by electroacupuncture in rats: dynorphin and kappa-opioid receptor implicated. Brain Research, 851(1-2): 290-296.