Education and Appointment:
Honors & Awards
Research Field of Interest:
Responding to the surrounding environment is one of the vital traits of a living organism. In particular sensing light is a most important perception and way of gathering information for most organisms. Dr. XUE’s lab is hence interested in understanding physiological characteristics and signaling mechanisms of photo-sensation, revealing neural circuits involved in this process and exploring methods for vision restoration after photoreceptor degeneration. “Light” does not only convey image information (image-forming vision), but also has impact on a number of physiological functions, such as light-entrainment of circadian rhythm, mood regulation, sleep, negative masking, pupillary light reflex, melatonin secretion etc. – functions referred to collectively as non-image vision (NIV). Only until recently, we realized that NIV is mediated by a special group of light-responsive cells in the retina: intrinsically photo-sensitive retinal ganglion cells (ipRGCs).
1. Neuronal Circuitry Involved in NIV
As compared to classic image-forming vision, we have very limited knowledge regarding the neuronal circuits involved in NIV. On-going projects in Dr. Xue’s lab focus on the mesoscopic structure and function of NIV-associated neuronal circuitry, using techniques such as trans-synaptic viral tracing, electrophysiology, optogenetics, and in vivo deep-brain calcium imaging.
2. Vision Rescue
Perception of light is of great importance, thus restoration of damaged photoreception (especially blindness caused by degeneration of rods and cones) is of high clinical value. One direction of Dr.XUE’s lab is to explore the possibilities in vision repair and rescue with a combinatorial approach employing stem cell regeneration, gene editing, and bio-informatics.
It is still not fully clear how ipRGCs control the unique kinetics of its light response through photo-transduction mechanisms, and what physiological significance this has for neuronal coding of NIV. We aim to investigate molecular targets that may affect the kinetics of ipRGC-mediated photo-responses, with the aid of transgenic mice, AAV-RNAi, patch-clamp and optogenetic techniques. We will further combine in vivo optogenetics with behavioral tests to reveal the coding pattern of ipRGC-mediated information, and its impact on NIV-associated physiological processes. This will expand our understanding about the strategy used by neural systems to code environmental stimuli for different physiological needs.
1.Ma Y#, Bao J#*, Zhang Y#, Li Z, Zhou Z, Zhou X, Wan C, Huang L, Zhao Y, Han G*, XueT*. Injectable, Self-powered Retinal Nanoantennae for the Creation of Mammalian Near-infrared Image Vision. Cell, 177, 1-13, 2019 (*co-corresponding authors lead contact)
2.Cai Y#, Cheng T#, Yao Y#, Li X, Ma Y, Li L, Zhao H, Bao J, Zhang M*, Qiu Z*, Xue T*In vivo genome editing rescues photoreceptor degeneration via a Cas9/RecA-mediated homology-directed repair pathway. Science Advances, Accepted (*co-corresponding authors lead contact)
3. Yu N, Huang L, Zhou Y*,Xue T*, Chen Z*, and Han G* (2019). Near-Infrared-Light Activatable Nanoparticles for Deep-Tissue-Penetrating Wireless Optogenetics.Adv Healthc Mater, e1801132. (*co-corresponding authors)
4.Zhu H#;Wang N#;Yao L; Chen Q; Zhang R; Qian J; Hou Y; Guo W; Fan S;Liu S; Zhao Q; Du F; Zuo X; Guo Y; Xu Y; Li J; Xue T; Zhong K; Song X; Huang G*;Xiong W*. Moderate UV exposure enhances learning and memory by promoting a novel glutamate biosynthetic pathway in the brain. Cell 173, 1716-1727 e1717. (2018)
5.Ye F, Huang Y, Li J, Ma Y, Xie C, Liu Z, Deng X, Wan J, Xue T, Liu W, Zhang M(2018). An unexpected INAD PDZ tandem-mediated plcbeta binding in Drosophila photo receptors. Elife 7.
6.Deng K, Shen J, Wang W, Li M, Li H, Chen C, Zhao H, Zhang M, Xue T, Liu Q, Lui VWY, Hong B, Lin W. Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small cell lung cancer. Cancer Biol Ther. 2018 Sep 5:1-13.
7.Deng WL, Gao ML, Lei XL, Lv JN, Zhao H, He KW, Xia XX, Li LY, Chen YC, Li YP, Pan D, Xue T, Jin, Z. B. Gene Correction Reverses Ciliopathy and Photoreceptor Loss in iPSC-Derived Retinal Organoids from Retinitis Pigmentosa Patients. Stem Cell Reports 2018, 10(4):1267-1281.
8.Tang J, Qin N, Chong Y, Diao Y, Yiliguma, Wang Z, Xue T, Jiang M, Zhang J,Zheng G: Nanowire arrays restore vision in blind mice. Nat Commun 2018, 9(1):786.
9.Cheng J, Huang X, Liang Y, Xue T, Wang L, Bao J: Plasticity of Light-induced concurrent Glutamatergic and GABAergic Quantal Events in the Suprachiasmatic Nucleus. J Biol Rhythms 2018, 33(1):65-75.
10.Li Q, Cui M, Yang F, Li N, Jiang B, Yu Z, Zhang D, Wang Y, Zhu X, Hu H, Li PS, Ning SL, Wang S, Qi H, Song H, He D, Lin A, Zhang J, Liu F, Zhao J, Gao L, Yi F, Xue T, Sun JP, Gong Y, Yu X. (2017) A cullin 4B-RING E3 ligase complex fine-tunes pancreatic δ cell paracrine interactions. J Clin Invest. 127(7):2631-2646.
11.Wang Q, Yue WWS, Jiang Z, Xue T, Kang SH, Bergles DE, Mikoshiba K, Offermanns S, Yau KW. (2017) Synergistic Signaling by Light and Acetylcholine in Mouse Iris Sphincter Muscle. Curr Biol. 27(12):1791-1800.
12.Zhao H, Ma YQ, An K, Hu JX, Cai Y, Bao J, Xue T. (2017) Phototransduction and brain circuitry of non-image-forming vision.Sci Sin Vitae, 2017, 47: 69–77.(review)
13.Liu CH, Gong Z, Liang ZL, Liu ZX, Yang F, Sun YJ, Ma ML, Wang YJ, Ji CR, Wang YH, Wang MJ, Cui FA, Lin A, Zheng WS, He DF, Qu C, Xiao P, Liu CY, Thomsen ARB, Joseph Cahill T, Kahsai AW, Yi F, Xiao KH, Xue T, Zhou Z, Yu X, Sun JP. (2017) Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling. Nat Communications 8:14335.
14.Wen M, Guo X, Sun P, Xiao L, Li J, Xiong Y, Bao J, Xue T, Zhang L, Tian C (2015) Site-specific fluorescence spectrum detection and characterization of hASIC1a channels upon toxin mambalgin-1 binding in live mammalian cells. Chem Commun (Camb)51(38):8153-6.
15.Hu QX, Dong JH, Du HB, Zhang DL, Ren HZ, Ma ML, Cai Y, Zhao TC, Yin XL, Yu X, Xue T, Xu ZG, Sun JP. (2014) Constitutive Gαi Coupling Activity of VLGR1 and its Regulation by PDZD7. J Biol Chem 289(35):24215-2
16.Zhong X, Gutierrez C, Xue T, Hampton C, Vergara MN, Park T, Zambidis E, Meyer J, Gamm MD, Yau KW, Canto-Soler MV (2014). Generation of three dimensional retinal tissue with functional photoreceptors from human iPSCs. Nature Communications5:4047.
17.Welsbie DS, Yang Z, Ge Y, Mitchell KL, Zhou X, Martin SE, Berlinicke CA, Hackler L Jr, Fuller J, Fu J, Cao LH, Han B, Auld D, Xue T, Hirai SI, Germain L, Simard-Bisson C, Blouin R, Nguyen JV, Davis CH, Enke RA, Boye SL, Merbs SL, Marsh-Armstrong N, Hauswirth WW, Diantonio A, Nickells RW, Inglese J, Hanes J, Yau KW, Quigley HA, Zack DJ. (2013). Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death. Proc Natl Acad Sci U S A. 110(10):4045-50.
18.Pearson RA, Barber AC, Rizzi M, Hippert C, Xue T, West EL, Duran Y, Smith AJ, Chuang JZ, Azam SA, Luhmann UFO, Benucci A, Sung CH, Carandini M, Yau KW, Sowden JC, Ali RR. (2012). Restoration of vision after transplantation of photoreceptors. Nature. 485(7396):99-103.
19.Xue T¶, Do MT, Riccio A, Jiang Z, Hsieh J, Wang HC, Merbs SL, Welsbie DS, Yoshioka T, Weissgerber P, Stolz S, Flockerzi V, Freichel M, Simon MI, Clapham DE, Yau KW¶. (2011). Melanopsin Signaling in Mammalian Iris and Retina. Nature. 479(7371):67-73. (Research Article) (¶ co-corresponding authors); Faculty of 1000:f1000.com/13360986.
20.Do MT, Kang SH, Xue T, Zhong H, Liao HW, Bergles DE, Yau KW. (2009) Photon capture and signalling by melanopsin retinal ganglion cells. Nature.457(7227):281-7. (Research Article); Faculty of 1000:f1000.com/1144855.
21.Luo DG, Xue T, Yau KW. (2008) How vision begins: An odyssey. Proc Natl Acad Sci U S A.105(29): 9855-62(review)
22.Fu YB*, Kefalov V*, Luo DG*, Xue T*, Yau KW. (2008) Quantal noise from human red cone pigment. Nature Neuroscience. 11(5):565-71 (* equal contributions)
23.Xue T, Siu CW, Lieu DK, Lau CP, Tse HF, Li RA. (2007) Mechanistic role of I(f) revealed by induction of ventricular automaticity by somatic gene transfer of gating-engineered pacemaker (HCN) channels. Circulation. 115(14):1839-1850.
24.El-Kholy W, MacDonald PE, Fox JM, Bhattacharjee A, Xue T, Gao X, Zhang Y, Stieber J, Li RA, Tsushima RG, Wheeler MB. (2007) Hyperpolarization-activated cyclic nucleotide-gated channels in pancreatic beta-cells. Mol Endocrinol.21(3):753-764.
25.Tse HF, Xue T, Lau CP, Siu CW, Wang K, Zhang QY, Tomaselli GF, Akar FG, Li RA (2006).A bio-artificial sinus node constructed via in vivo gene transfer of an engineered pacemaker (HCN) channel reduces the dependence on electronic pacemaker in a sick sinus syndrome model.Circulation114: 1000-1011. Issue highlights, GROUND-BREAKING STUDY OF 2007 AHA.
26.Ardehali H, Xue T, Dong P, Machamer C (2005).Targeting of the mitochondrial membrane proteins to the cell surface for functional studies.Biochem Bioph Res Comm. 338(2):1143-51.
27A.braham MR, Henrikson CA, Tung L, Chang MG, Aon M, Xue T, Li RA, O'Rourke B, Marban E (2005).Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation.Circ Res. 97:159-67.
28.Moore JC, van Laake LW, Braam SR, Xue T, Tsang SY, Ward D, Passier R, Tertoolen LL, Li RA, Mummery CL (2005). Human embryonic stem cells: Genetic manipulation on the way to cardiac cell therapies. Reprod Toxicol. 20:377-91.
29.Azene EM, Xue T, Marban E, Tomaselli GF, Li RA (2005).Non-equilibrium behavior of HCN channels: Insights into the role of HCN channels in native and engineered pacemakers.Cardiovasc Res. 67:263-73.
30.Wang G*, Xue T*, Tsang SY, Wong J, Cheng L, Zhang J, Li GR, Lau CP, Li RA, Tse HF (2005).Electrophysiological properties of pluripotent human and mouse embryonic stem cells.Stem Cells. 23(10):1526-34. (* equal contributions)
31.Xue T*, Cho H*, Akar F*, Tsang SY, Jones S, Marbán E, Tomaselli GF, Li RA (2005).Functional Integration of Electrically Active Cardiac Derivatives from Genetically Engineered Human Embryonic Stem Cells with Quiescent Recipient Ventricular Cardiomyocytes. Insights into the Development of Cell-Based Pacemakers. Circulation. 111:11-20. issue highlights, (Best Paper Award, Circulation. 2005) (* equal contribution)
32.Xue T, Sato K, Kodama K, Ennis I, French RJ, Li RA (2003).Novel interactions identified between µ-conotoxin and the Na+ channel Domain I P-loop: Implications for toxin-pore binding geometry. Biophys. J.85(4):2299-310.
33.Azene EM*, Xue T*, Li RA (2003).Molecular basis of the effects of potassium on heterologously-expressed pacemaker (HCN) channels.J. Physiol. (London) 547(2):349-356. (* equal contributions )
34.Henrikson CA, Xue T, Dong P, Sang D, Marbán E, Li RA (2003).Identification of a surface charged residue in the S3-S4 linker of pacemaker (HCN) channel that influences activation gating.J. Biol. Chem. 278(16):13647-54.
35.Li RA, Ennis I, Xue T, Nguyen HM, Tomaselli GF, Goldin AL, Marbán E (2003).Molecular basis of isoform-specific µ-conotoxin block of cardiac, skeletal muscle and brain Na channels. J. Biol. Chem. 278(10):8717-24.
36.Xue T, Li RA (2002).An external determinant in the S5-P linker of the pacemaker (HCN) channel identified by sulfhydryl modification.J. Biol. Chem.277(48):46233-42.
37.Xue T, Marbán E, Li RA (2002).Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker currents by an engineered HCN1 construct: Insights into structure-function relationships and multimerization.Circ. Res.90:1267-1273.
38.Li RA, Sato K, Kodama K, Kohno T, Xue T, Tomaselli GF, Marban E. (2002). Charge conversion enables quantification of the proximity between a normally-neutral mu-conotoxin (GIIIA) site and the Na+ channel pore. FEBS Lett.511(1-3):159-164.
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