骨干人才

薛 天
薛天,男,1977年出生,博士,中国科学技术大学人力资源部部长,生命科学与医学部执行部长,生命科学学院教授、博导、执行院长,微尺度物质科学国家研究中心“神经环路与脑认知部”主任。长期从事光感受神经生物学的光信号转导、神经环路以及视觉再生修复等方面研究。至今共发表SCI论文40余篇,多篇通讯作者论文发表在Nature、Cell、Nature Neuroscience等学术期刊,被引用3500余次, h-index 24。工作入选2019年度“中国生命科学十大进展”,Cell杂志2019年最佳论文。获国家自然科学基金委杰出青年基金(2019)、优秀青年基金 (2013),科技部国家重大科学研究计划青年973项目首席科学家(2013),中科院脑科学卓越中心骨干(2014),获国际研究资助组织Human Frontier Science Program (HFSP) Young Investigator Grants(2014)。担任教育部高等学校生物技术与生物工程类专业教学指导委员会委员、中国生理学会常务理事、中国神经科学学会、中国细胞生物学学会理事、中国生物物理学会组织建设工作委员会主任等学术任职。
主要研究方向及内容
感知外界环境作出相应反应是生命体的最基本特征。而对于光信号的感知是多数生命体最重要的感知功能和信息输入方式。因此本实验室致力于了解神经光感受的生理特性、信号转导机理、神经环路基础并探索修复受损视觉的方法。“光”不但能帮助我们获得图像感知(成像视觉Image vision)还控制一系列重要的生理功能,包括生物钟的光调节,情绪调节,睡眠,畏光,瞳孔光反射,褪黑素表达等,这些统称为“非成像视觉”功能(non-image-forming vision)。 直到近年来我们才逐渐认识到介导这些非成像视觉的感光细胞是在视网膜中的自感光视网膜神经节细胞 (ipRGC)。
1.非成像视觉感光机理和神经信号编码
我们一直不清楚ipRGCs是如何通过其光信号转导机制控制它独特的光反应动力特征的,以及这些感光特性对于非成像视觉神经信号编码的生理意义。我们将利用小鼠基因工程、细胞膜片钳结合光刺激、AAV介导RNAi等技术方法研究ipRGCs光信号转导中反应动力学相关的分子位点。进一步结合动物行为学和光遗传学等手段解析ipRGCs信息处理规律,及其神经编码方式对非成像感光生理功能的影响。 这些认知将有可能在更广泛的层次上帮助我们理解神经感受器官对于外界刺激根据不同生理功能需求而进行编码处理的策略。
2.非成像视觉神经环路
相对于经典的成像视觉环路,我们对于非成像视觉神经环路,特别是视网膜--下丘环路的结构和功能却知之甚少。我们希望通过特异荧光标记、跨突触病毒示踪、在体深部脑区功能钙成像、电生理、光遗传、高场小动物fMRI、行为学等手段,解析非成像视觉(特别是光控情绪)环路的介观环路结构以及其行使功能的工作模式。
3.视觉修复
光信号感知是如此重要,如何治疗光感受细胞受损(特别是成像视觉的视锥视杆退化导致的眼盲)就具有相当重要的意义。我们的另一个重要研究方向将是通过多能干细胞再生、在体转分化等手段探索再生和修复感光细胞用以治疗受损视觉的新方法。
代表性论文
An K#, Zhao H#*, Miao Y, Xu Q, Li YF, Ma YQ, Shi YM, Shen JW. Meng JJ, Chen JT, Bao J, and Xue T*? (2020). A Circadian Rhythm-gated Subcortical Visual Circuit for Nighttime Light Induced Depressive-like Behaviors, Nat. Neurosci. Accepted. (# equal contributions, *co-corresponding authors,?lead contact)
Lu Y#, Shiau F#, Yi W#, Lu S, Wu Q, Pearson J, Kallman A, Zhong S, Hoang T, Zuo Z, Zhao F, Zhang M, Tsai N, Zhuo Y, He S, Zhang J, Stein-O’Brien G, Sherman T, Duan X, Fertig D, Goff L, Zack J, Handa J, Xue T*, Bremner R*, Blackshaw S*,Wang X* and Clark B*? (2020). Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development. Dev. Cell. Accepted.
Xie H#, Zhang W#, Zhang M#*, Akhtar T, Li Y, Yi W, Sun X, Zuo Z, Wei M, Fang X, Yao Z, Dong K, Zhong S, Liu Q, Shen Y, Wu Q, Wang X, Zhao H, Bao J, Qu K*, Xue T*? (2020). Chromatin accessibility analysis reveals regulatory dynamics of developing human retina and hiPSC derived retinal organoids. Sci. Adv. 6, eaay5247.
Akhtar T, Xie H, Khan MI, Zhang M*, Xue T*? (2019). Accelerated photoreceptor differentiation of hiPSC-derived retinal organoids by contact co-culture with retinal pigment epithelium, Stem Cell Res., 39, 101491.
Ma Y#, Bao J#*, Zhang Y#, Li Z, Zhou Z, Zhou X, Wan C, Huang L, Zhao Y, Han G*, Xue T*? (2019). Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae. Cell 177, 243-255 e215. Cell Best of 2019, Cell press (9 Best Articles which published in Cell in 2019)
Cai Y#, Cheng T#, Yao Y#, Li X, Ma Y, Li L, Zhao H, Bao J, Zhang M*, Qiu Z*, Xue T*? (2019). In vivo genome editing rescues photoreceptor degeneration via a Cas9/RecA-mediated homology-directed repair pathway. Sci Adv 5, eaav3335.
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. (review)
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, 67-73. (Faculty of 1000: f1000.com/13360986).
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, 281-7. (Faculty of 1000: f1000.com/1144855).
Luo DG, Xue T, Yau KW (2008) How vision begins: An odyssey. PANS 105, 9855-62 (review)
Fu YB#, Kefalov V#, Luo DG#, Xue T#, Yau KW (2008). Quantal noise from human red cone pigment. Nat. Neurosci. 11, 565-71
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, 1839-1850.
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. Circulation 114, 1000-1011. Issue highlights, GROUND-BREAKING STUDY OF 2007 AHA.
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, 1526-34.
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 11, 111-20. Issue highlights, Best Paper Award, Circulation 2005
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, 2299-310.
Azene EM#, Xue T#, Li RA (2003). Molecular basis of the effects of potassium on heterologously-expressed pacemaker (HCN) channels. J. Physiol. 547, 349-356.
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, 46233-42.
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.
实验室网址:http://biox.ustc.edu.cn/szdw/zzbqnqrjh/201207/t20120710_137907.html
E-mail: xuetian@ustc.edu.cn
电话:0551-63600967