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个人简介

1989年获得英国剑桥大学博士学位(Ph.D. in Pharmacology),1990-1994在美国耶鲁大学、哈佛大学做博士后研究。1994-1998在中国农业大学生物学院/农业生物技术国家重点实验室任副教授。1998年至今任北京师范大学细胞生物学教授(Professor in Pancreatic Acinar Cell Physiology)、首任所长、博导。1996年获HFSP资助,1998年入选教育部跨世纪人才计划,同年获国家杰出青年科学基金。1999年获国务院政府特殊津贴。现为《Biophysics Reports》副主编,《生理科学进展》、《The Pancreapedia》、《BioCell》、《J Biol Reg Homeost Ags》等编委。曾任中国细胞生物学会理事,中国生物物理学会理事兼光生物物理学专业委员会主任委员。自2011年至今为本科生共同主讲国家精品课程《人体与动物生理学》。 国家自然科学基金委项目 2013-2016 中性白(粒)细胞活动调节胰腺腺泡细胞钙信号 2017-2020 利用亚细胞定位表达的蛋白质光敏剂光动力调控G蛋白偶联受体 2020-2023 “嘎嘣脆”受体(GPCR-ABSO)基因编码光动力激活的基本特性研究 2023-2026 NAD(P)H氧化酶5的光驱激活及其机制研究

研究领域

胞浆钙振荡发生机制(generation of calcium oscillations):体内所有细胞受到生理性刺激后,所产生的最早的反应之一是胞浆中钙离子浓度的升高。钙离子浓度的升高在单个细胞水平是以振荡的形式出现的,即钙离子浓度随着时间的变化出现很规则的钙峰。钙振荡的出现使得胞浆钙离子浓度可以同时进行两种方式的调制,即振幅调制(AM)、频率调制(FM)。因而通过振荡的方式胞浆钙离子浓度变化可以编码成复杂多样的信号,使得钙离子可以特异性调控细胞的多种功能。本实验室的一个主要方向是研究在各种不同的分泌细胞和其它细胞中钙振荡发生的机制,如Na+/Ca2+交换蛋白、ER钙离子通道与振荡起博的关系。 细胞分泌的分子基础(molecular basis of exocytosis):分泌细胞在体内占据有重要位置。如胰腺腺泡细胞、胰腺内分泌细胞、垂体前叶细胞、乳腺上皮细胞等在细胞水平都具有一定的共同点,即细胞受到刺激后,细胞胞浆中的分泌颗粒与细胞质膜搭联、融合,将分泌颗粒的内容物排出胞外。本实验室重点研究分泌细胞受到刺激后是如何使得分泌颗粒与细胞质膜搭联、融合,产生胞吐,完成细胞分泌过程的,如SNARE蛋白及相关蛋白的作用。 单线态氧在细胞信号转导中的作用(singlet oxygen as a signaling molecule):在自然界中存在有多种可以特异性吸收一定波长光子的化合物。某些化合物吸收一定波长的光子后可以将所吸收的光能转移给分子氧,产生单线态氧分子。因为单线态氧分子具有极高的化学势能(94 kJ/mole),在细胞内寿命极短(1μs),因而其有效反应距离局限在< 10 nm。所以光动力作用过程中所产生的单线态氧分子可以亚细胞特异性地调控细胞功能。本实验室重点研究光动力作用在胞内的分子靶点及其对具有重要生命意义的信号转导分子靶点的化学修饰,并探讨单线态氧分子作为内源性信使发生的分子基础。使用基因编码的蛋白质光敏剂(毒杀红KillerRed、迷你单miniSOG),产生亚细胞器特异性定位、细胞类型特异性定位、中枢或外周神经核团特异性定位的单线态氧分子。发现目前唯一的一个可被单线态氧分子永久性激活的G蛋白偶联受体(GPCR-ABSO,对应中文名词初步表征为“嘎嘣脆”受体)。 细胞之间的接触性相互作用(cell contact interactions):研究中性粒细胞呼吸爆发、胰腺星形细胞激活,对胰腺腺泡细胞功能的调节作用。发现中性粒细胞对胰腺腺泡细胞胞浆钙振荡的湮灭作用,以及胰腺星形细胞对胰腺腺泡细胞胞浆钙振荡的刹车作用。 川楝素与突触传递(toosendanin on synapse):研究川楝素对突触传递调控的细胞与分子基础。研究了川楝素对感觉神经元(结节神经元)钙信号和胞吐过程的刺激作用。

近期论文

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Research articles Li Y, Cui ZJ (2022) Transmembrane domain 3 (TM3) is a transplantable pharmacophore in the photodynamic activation of cholecystokinin 1 receptor. ACS Pharmacol Transl Sci 5: 539-547. https://doi.org/10.1021/acsptsci.2c00031 Li Y, Cui ZJ (2022) Photodynamic activation of the cholecystokinin 1 receptor with tagged genetically encoded protein photosensitizers: Optimizing the tagging patterns. Photochem Photobiol 98. www.doi.org/10.1111/php.13611 Zhang SJ, Li ZH, Zhang YD, Chen J, Li Y, Wu FQ, Wang W, Cui ZJ, Chen GQ (2021) Ketone body 3-hydroxybutyrate ameliorates atherosclerosis via receptor Gpr109a-mediated calcium influx. Adv Sci 2021: 2003410. Li Y, Cui ZJ (2020) NanoLuc bioluminescence-driven photodynamic activation of cholecystokinin 1 receptor with genetically encoded protein photosensitiser miniSOG. Intl J Mol Sci 21: 3763. https://www.mdpi.com/1422-0067/21/11/3763 Tang WZ, Cui ZJ (2020) Permanent photodynamic activation of the cholecystokinin 2 receptor. Biomolecules 10: 236. https://www.mdpi.com/2218-273X/10/2/236 Liu JS & Cui ZJ (2019) Pancreatic stellate cells serve as a brake mechanism on pancreatic acinar cell calcium signaling modulated by methionine sulfoxide reductase expression. Cells 8: 109. https://www.mdpi.com/2073-4409/8/2/109 Guo HY & Cui ZJ (2019) Extracellular histones activate TLR9 to induce calcium oscillations in rat pancreatic acinar tumor cell AR4-2J. Cells 8: 3. https://www.mdpi.com/2073-4409/8/1/3 Jiang WY, Li Y, Li ZY & Cui ZJ (2018) Permanent photodynamic cholecystokinin 1 receptor activation-dimer-to-monomer conversion. Cell Mol Neurobiol 38: 1283-1292. https://link.springer.com/article/10.1007%2Fs10571-018-0596-3 Jiang HN, Li Y, Jiang WY & Cui ZJ (2018) Cholecystokinin 1 receptor-a unique G protein-coupled receptor activated by singlet oxygen (GPCR-ABSO). Front Physiol 9: 497. https://www.frontiersin.org/articles/10.3389/fphys.2018.00497/full Liang HY, Song ZM & Cui ZJ (2013) Lasting inhibition of receptor-mediated calcium oscillations in pancreaticacini by neutrophil respiratory burst - a novel mechanism for secretory blockade in acute pancreatitis? BiochemBiophys Res Commun 437: 361-367. Jia YH & Cui ZJ (2011) Tri-phasic modulation of ACh- and NE-maintained calcium plateau by high potassium in isolated mouse submandibular granular convoluted tubular cells. Arch Oral Biol 56: 1347-1355. Fang XF & Cui ZJ (2011) The anti-botulism triterpenoid toosendanin elicits calcium increase and exocytosis in rat sensory neurons. Cell Mol Neurobiol 31: 1151-1162. Duan YJ, Liang HY, Jin WJ, Cui ZJ (2011) Substance P conjugated to CdTe quantum dot triggers cytosolic calcium oscillations and induces QD internalization in the pancreatic carcinoma cell line AR4-2J. Analyt Bioanalyt Chem 400: 2995-3003. Chen BD, Guan DD, Cui ZJ, Wang X & Shen X (2010) Thioredoxin 1 downregulates MCP-1 secretion and expression in human endothelial cells by suppressing nuclear translocation of activator protein 1 and redox factor-1. Am J Physiol Cell Physiol 298: C1170-C1179. Wang BJ, Liang HY & Cui ZJ (2009) Duck pancreatic acinar cell as a unique model for independent cholinergic stimulation-secretion coupling. Cell Mol Neurobiol 29: 747-756. Zhou YD, Fang XF & Cui ZJ (2009) UVA induced calcium oscillations in rat mast cells. Cell Calcium 45: 18-28. (Zhou YD: https://profiles.psu.edu/profiles/display/73800983) Hu F, Sun WW, Zhao XT, Cui ZJ & Yang WX (2008) TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry-dependent ROS production and mitochondrial depolarization. Biochem Biophys Res Commun 369: 989-993. Ma CY & Cui ZJ (2004) Selective use of a reserved mechanism for inducing calcium oscillations. Cell Signal 16: 1435-1440. Xiao R & Cui ZJ (2004) Mutual dependence of VIP/PACAP and CCK receptor signaling for a physiological role in duck exocrine pancreatic secretion. Am J Physiol 286: R189-R198. (Xiao R: http://aging.ufl.edu/profile/rui-xiao-ph-d/) Cui ZJ, Zhou YD, Satoh Y & Habara Y (2003) A physiological role for protoporphyrin IX photodynamic action in the rat Harderian gland? Act Physiol Scand 179: 149-154. An YP, Xiao R, Cui H & Cui ZJ (2003) Selective activation by photodynamic action of cholecystokinin receptor in the freshly isolated rat pancreatic acini. Br J Pharmacol 139: 872-880. Reviews Jiang HN, Li Y & Cui ZJ (2017) Photodynamic physiology-photonanomanipulations in cellular physiology with protein photosensitisers. Front Physiol 8: 191. https://www.frontiersin.org/articles/10.3389/fphys.2017.00191/full Cui ZJ, Han ZQ & Li ZY (2012) Modulating protein activity and cellular function by methionine residue oxidation. Amino Acids 43: 505-517. Wang BJ & Cui ZJ (2007) How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans. Am J Physiol 292: R666-R678.

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