崔宗杰    博士 

Zong Jie Cui, PhD (Cantab.), Professor

Beijing Normal University, Beijing 100875, China

教授、博士生导师

联系方式：010-58809162 (Tel)

电子邮件：zjcui@bnu.edu.cn

个人主页：http://cls.bnu.edu.cn/cls_old/...

客座教授：Michael Xi Zhu, Ph.D., Professor, The University of Texas Health Science Center at Houston, Dept. Integr Biol Pharmacol (http://ibp.med.uth.tmc.edu/faculty/bio-zhu-michael.html)      

个人简介

1989年获得英国剑桥大学博士学位，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教授、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》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。共同主讲国家精品课程《人体与动物生理学》。

实验室研究方向与内容

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、迷你单)，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。

招生目录： 071009 细胞生物学专业 –  分泌细胞的信号转导

代表性论文

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 

Jiang HN, Li Y, Cui ZJ (2017) Photodynamic physiology - photonanomanipulations in cellular physiologywith protein photosensitisers. Front Physiol 8: 191.  https://www.frontiersin.org/articles/10.3389/fphys.2017.00191/full 

Li ZY, Jiang WY, Cui ZJ (2015) An essential role for NAD(P)H oxidase 2 inUVA-induced calcium oscillations in mast cells. Photochem Photobiol Sci 14: 414-428.

Liang HY, Song ZM, Cui ZJ (2013) Lasting inhibition of receptor-mediated calcium oscillations in pancreaticacini by neutrophil respiratory burst - a novel mechanism for secretoryblockade in acute pancreatitis? BiochemBiophys Res Commun 437: 361-367.

Cui ZJ, Han ZQ, Li ZY (2012)  Modulating protein activity and cellular function by methionine residue oxidation. Amino Acids 43: 505-517.

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. (Yan Dong Zhou: 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.

Wang BJ & Cui ZJ (2007) How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans. Am J Physiol 292: R666-R678.

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.  (Rui Xiao: 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.

Publications List on 11 Feb. 2019

ZJCui Publications List 2019.pdf

国家自然科学基金委项目:

1/      2010-2012, 大鼠肥大细胞胞浆钙振荡。

2/      2013-2016, 中性白细胞活动调节胰腺腺泡细胞钙信号。

3/      2017-2020, 蛋白质光敏剂光动力调控G蛋白偶联受体。

国家科技部项目:

4/ 2011-2015, 细胞钙信号的时空特异性调控。

Zong Jie Cui, PhD (Cantab.) (1989)(Year of Birth, 1964) 

Professor and Founding Director,

Inst Cell Biol, Beijing Normal University, Beijing 100875, China

Tel:86 10 5880 9162

E-mail：zjcui@bnu.edu.cn

Webpage：http://cls.bnu.edu.cn/cls_old/...

Guest Professor：Michael Xi Zhu, Ph.D., Professor, The University of Texas Health Science Center at Houston, Dept. Integr Biol Pharmacol (http://ibp.med.uth.tmc.edu/faculty/bio-zhu-michael.html)

Biography

M.Phil. and Ph.D. in pharmacology, University of Cambridge, 1986, 1989;

Postdoctoral positions, Dept. Pharmacology, Yale Univ. School of Medicine, and Dept. of Surgery, Harvard Medical School and Beth Isreal Hospital, 1990-1994;

Associate Professor, National Laboratory of Biotechnology, China Agricultural Univ, 1994-1998;

Professor in Cell Biology, Beijing Normal University, 1998- present.

A Short-Term Fellowship from The HFSP, 1996.

The China Ministry of Education Trans-Century Talent Programme, 1998.

Young Scientist Merrit Award, NSFC, 1998.

A Special Stipend from The Chinese State Council, 1999.

Editorial boards: Prog Physiol Sci, Biophysics Reports (Associate Editor), Pancreapedia.

Formerly Council Member, Chinese Society for Cell Biology, Chinese Biophysical Society.

Past President, Chinese Commission for Photobiology (a section of The Chinese Biophysical Society).

Undergraduate course (Nationally Acclaimed Course): Human and Animal Physiology.

Research Interests

Cytosolic calcium oscillations:

Among the earliest responses after cellular stimulation is increase in cytosolic calcium concentration. Such calcium increases in individual cells are often in the form of oscillations - periodic increases in cytoslic calcium concentrtion. Oscillation confers two forms of modultion of the calcium signal: amplitude modultion (AM), and frequency modultion (FM), therefore multiple calcium signals could be encoded, to modulate specific cellular functions. Our laboratory investigates in secretory and other cell types the molecular mechanisms of calcium oscillations, such as a role for NCX, ER calcium channels in the pace-making process of calcium oscillations.

Molecular basis of exocytosis:

Secretory cells are pivotal in the body. Secretory cells such as pancreatic acinar cells, pancreatic islet beta cells, anterior pituitary cells, mamary gland acinar cells, after stimulation by neurotransmitters or hormones all have their secretory granules in the cytosol to dock at, and fuse with, the plasma membrane, subsequently to release the granule content into the extracellular space. Our laboratory investigates how after stimulation, secretory cells have their secretory granules dock at, and fuse with plasma membrane, to complete the process of exocytosis and cell secretion, with an emphasis on SNARE and related proteins.

Singlet oxygen as a signaling molecule:

Many chromophores (photon-absorbing groups) in nature could absorb photons of certain wavelength. When such molecules after absorption of photons transfer their photon energy to molecular oxygen, the excited delta singlet oxygen is produced. Since singlet oxygen has very high chemical energy (94 kJ/mole), and a very short lifetime in cellular environment (１μs), it has very limited distance of effective reaction (< 10 nm). Therefore singlet oxygen generated during a Type II photodynamic action could subcellular specifically modulate cellular functions. Our laboratory investigates molecular targets of photodynamic action in alive cells, and the resultant chemical modifications of biologically important signalling macromolecules.  We also investigate the molecular basis of singlet oxygen action as an endogenous signalling molecule. The genetically encoded protein photosenstisers (KillerRed, miniSOG) were subcellular organelle specifically or cell type specifically expressed to generate highly spatially defined molecular singlet oxygen. We found that the plasma membrane-localized G protein-coupled receptor cholecystokinin 1 (CCK1) receptor is permanently activated by singlet oxygen (ABSO), we therefore named CCK1 receptor a GPCR-ABSO. 

Contact regulation between neighbouring cell types:

To investigate regulation by neutrophil respiratory burst, pancreatic stellate cell activation on pancreatic acinar calcium signalling. We found that neutrophils can quench CCK- and ACh-induced calcium oscillations in rat pancreatic acinar cells. Further, rat pancreatic stellate cells were found to serve as a brake mechanism on pancreatic acinar cell calcium signaling.

Modulation of synaptic transmission by toosendanin:

To examine the cellular and molecular effects of toosendanin on synaptic transmission. We found that toosendanin elicits calcium increases and exocytosis in rat sensory neurons (nodose ganglion neurons).

Recruitments for MPhil and PhD students:

071009 Cell Biology – Signalling in secretory cells

FOR OVERSEAS STUDENTS:

PLEASE SEND

1/ OFFICIAL TRANSCRIPTS OF UNDERGRADUATE AND GRADUATE ACADEMIC SCORES,

2/ OFFICIAL REFERENCES FOR BOTH UNDERGRADUATE AND POSTGRDUATE EDUCATION,

3/ CERTIFICATE FOR ENGLISH PROFICIENCY.

Representative Publications 

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.

Guo HY, Cui ZJ (2019) Extracellular histones activate TLR9 to induce calcium oscillations in rat pancreatic acinar tumor cell AR4-2J. Cells 8: 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. 

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.  

Jiang HN, Li Y, Cui ZJ (2017) Photodynamic physiology - photonanomanipulations in cellular physiologywith protein photosensitisers. Front Physiol 8: 191.

Li ZY, Jiang WY, Cui ZJ (2015) An essential role forNAD(P)H oxidase 2 inUVA-induced calcium oscillations in mast cells. Photochem Photobiol Sci 14: 414-428.

Liang HY, Song ZM, Cui ZJ (2013) Lasting inhibition of receptor-mediated calcium oscillations in pancreaticacini by neutrophil respiratory burst - a novel mechanism for secretoryblockade in acute pancreatitis? BiochemBiophys Res Commun 437: 361-367.

Cui ZJ, Han ZQ, Li ZY (2012) Modulating protein acvitity and cellular function by methionine residue oxidation. Amino Acids 43: 505-517.

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. (Yan Dong Zhou: 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.

Wang BJ & Cui ZJ (2007) How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans. Am J Physiol 292: R666-R678.

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.  (Rui Xiao: 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.

Publications List on 11 Feb. 2019

ZJCui Publications List 2019.pdf

Research Grants from NSFC:

1/      2010-2012, Cytosolic calcium oscillations in rat mast cells.

2/      2013-2016, Neutrophil regulation of calcium signalling in pancreatic acini.

3/      2017-2020, Protein photosensitizer photodynamic regulation of GPCR.

Research Grant from MOST:

4/ 2011-2015, Spatial and Temporal Regulation of Cell Calcium Signal.

Major professional contributions:

1/ Confirmed cholecystokinin (CCK) as a physiological secretagogue in exocrine pancreatic secretion in birds (chickens, ducks)

Physiological concentrations of CCK had significant effects on duck pancreatic acianr cell secretion only after activation of cAMP-mobilizing VIP/PACAP receptor. [From: 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: R189-198.]

Activation of the cAMP-mobilizing VIP/PACAP receptor shifts CCK dose-response curve to the left, but has no effect on ACh dose-response curve in duck pancreatic acinar cells. [From: 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.]

2/ Discovered singlet oxygen-induced permanent activation of CCK1 receptors in rodent pancreatic acinar cells and associated cytosolic calcium oscillations 

Singlet oxygen produced during type II photodynamic action triggered permanent cytosolic calcium oscillations in freshly isolated rat pancreatic acini. [From: Cui ZJ & Kanno T (1997) Selective activation by photodynamic action of cholecystokinin receptor in the freshly isolated rat pancreatic acini. J Physiol (Lond) 504: 47-55.]

Singlet oxygen triggered cytosolic calcium oscillations during photodynamic action were due to selective but permanent activation of CCK1 receptors in freshly isolated rat pancreatic acinar cell. [From: 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.]

Singlet oxygen resulted in the permanent activation of CCK1 receptors in freshly isolated rat pancreatic acinar cells, but had no effect on M3 muscaranic receptor activation or cytosolic calcium oscillations induced by ACh. [From: 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.]

3/ Discovered the very 1st G protein-coupled receptor permanently activated by singlet oxygen (GPCR-pABSO)

CCK1R either in AR4-2J cells, or ectopically expressed could all be permanently activated by singlet oxygen generated by photodynamic action with either chemical photosensitiser SALPC or genetically encoded protein photosensitiser KillerRed or miniSOG. Further, CCK1R fusion expressed with either KillerRed or miniSOG are also permanently activated after light irradiation. 

From: 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.

CCK1R protein extracted from isolated rat pancreatic acini, are quantitatively converted from dimer to monomers by SALPC photodynamic action. 

From:  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.

Although no such conversion is observed after CCK stimualtion, subthreshold photodynamic action plus CCK revealed a "Bell-Shaped" CCK dose response curve which is very similar to CCK-stimulated amylase release from isolated rat pancreatic acini.

From:  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.

4/ Discovered the basal plasma membrane TLR9 coupling to the calcium signaling pathway

From: Guo HY, Cui ZJ (2019) Extracellular histones activate TLR9 to induce calcium oscillations in rat pancreatic acinar tumor cell AR4-2J. Cells 8: 3.

5/ Pancreatic stellate cells brake on the pancreatic acinae cell calcium signaling

From: Liu JS, Cui ZJ (2019) Pancreatic stellate cells serve as a brake mechanism on pancreaticnacinar cell calcium signaling modulated by methionine sulfoxide reductase expression. Cells 8: 109.