熊志奇博士简介

生物谷

Zhi-Qi Xiong, Ph.D.

Room 426, ION Building
Institute of Neuroscience
Chinese Academy of Sciences
Shanghai 200031
China
Phone: 86-21-54921716
Email: xiongzhiqi@ ion.ac.cn

1987年－1992年华西医科大学药学专业，学士
1992年－1995年中国科学院上海药物所神经药理学专业，硕士
1995年－2000年美国贝勒医学院药理学和神经科学专业，博士
2000年－2003年美国杜克大学医学中心Dr. James O. McNamara实验室，博后研究
2003年－美国杜克大学神经生物学系，客座助理教授
2003年－中国科学院神经科学研究所，研究员

神经系统疾病例如癫痫、中风、Alzheimer 症、 Rett综合症和Rasmussen脑炎等,正威胁着成千上万不同年龄阶段人们的健康和生命，不但引发了很多社会经济问题,还给医学界提出了严重的挑战。目前，人们已经积累了大量关于神经系统疾病的临床，病理，生化和药理学方面的知识，并且广泛应用了针对疾病临床症状的治疗手段。但是，对于神经系统疾病的发病机制，人们还知之甚少，同时我们也非常缺乏针对发病机制的预防和治疗手段。本实验室将运用细胞分子生物学，生物化学方法，同时结合转基因及基因敲除小鼠技术、神经电生理学、神经影像学技术，逐步揭示神经系统疾病在细胞水平和分子水平的发病机制，同时还将针对性地探讨疾病的预防、诊断和治疗手段。

神经退行性疾病小鼠模型的建立
神经退行性疾病的显著特征是特定神经元群体的选择性死亡，例如在Alzheimer症、Parkinson症、Huntington症和肌萎缩性(脊髓) 侧索硬化症中都会发生神经元群体的继发性死亡。目前对于单基因突变引起的一系列家族性遗传病的鉴定和致病基因的克隆，为神经退行性疾病的分子机制研究奠定了牢固的基础。我们实验室的兴趣在于神经退行性疾病小鼠模型的建立和转基因小鼠发病机制的研究。
在特定的转基因小鼠中，突变基因可以在中枢神经系统的特定神经元中被时间特异性的调控表达。我们将利用这一特性探究神经退行性疾病的发病机制和确定发病过程的初始事件。我们用绿色荧光蛋白标记特异的神经元,并将观察转基因小鼠中突变基因在单个标记神经元中的表达情况。上述转基因小鼠模型和标记技术的应用，将为进一步探索突变蛋白对神经元发育和功能的影响提供强有力的手段和证据。

脑损伤后神经兴奋性和可塑性的研究：
人们研究表明，严重的大脑损伤会导致急性的神经元死亡,从而引起长时间的神经系统功能丧失。我们对该现象的分子机制非常感兴趣，特别关注于诸如中风，高烧惊厥，脑膜炎，脑炎等脑损伤导致的癫痫发生机制。在中国,癫痫病困扰着近900万不同年龄阶段的患者。本实验室试图通过mRNA assay和功能蛋白质组分析来建立脑损伤和癫痫发生的分子联系,从而研究和阐明发病机制,这将会为癫痫的临床预防和治疗提供有效的药物作用靶点。

Dr. Zhi-Qi Xiong received his Bachelor's degree in Pharmacy in 1992 from West China University of Medical Sciences (Sichuan University), MS in 1995 from Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Ph.D. in 2000 from Baylor College of Medicine. He was a postdoctoral research associate in the laboratory of Dr. James O. McNamara at Duke University Medical Center from 2000 to 2003. He is currently an Investigator and the head of the lab of neurobiology of disease at ION.

Research Interests
	Diseases of the nervous system, ranging from epilepsy, stroke, and Alzheimer's disease, which affect millions, to rare ones such as Rett's syndrome and Rasmussen's Encephalitis, have devastating consequences for individuals of all ages and represent increasing medical and socioeconomic problems. Although symptomatic treatments are available in some diseases, mechanism-based therapies to prevent or cure these diseases are lacking. Our goal is to understand neurological diseases in cellular and molecular terms and to develop rational treatments.

	Ongoing Projects
	Modeling human neurodegenerative diseases in mice Progressive loss of discrete populations of neurons is the hallmark of human neurodegenerative diseases such as Alzheimer¡¯s disease, Parkinson¡¯s disease, Huntington¡¯s disease, amyotrophic lateral sclerosis and others. The identification of causative single-gene mutations in a subset of families with inherited disorders has provided a powerful strategy to define the molecular mechanisms of neurodegeneration. We are interested in generating transgenic mice in which the mutant proteins can be selectively expressed in CNS neurons in a temporally controlled manner. These mice will be potentially valuable for investigating the pathogenic triggers and for identifying the initiating events in the neurodegenerative process. We are also interested in generating transgenic mice that will allow us to express the mutant proteins in single neurons and label the same neurons with green fluorescent protein. These mice will be extremely useful for investigating the early impacts of these mutant proteins on neuronal development and function. Neuronal excitability and plasticity following brain injury In addition to acute neuronal cell loss, serious injuries to the brain can cause long-term neurological deficits. We are interested in the molecular mechanisms by which acute brain injuries cause long-term neurological deficits. In particular, we are interested in the mechanisms of epileptogenesis following brain injuries. Epilepsy, which affects approximately nine million Chinese of all ages, may develop after common brain insults, including stroke, trauma, febrile seizures, meningitis and encephalitis. We seek to identify the molecules that link brain injuries to epileptogenesis, using mRNA display and functional proteomics technologies. Identification of such molecules will provide novel targets for therapeutic intervention to prevent or cure epilepsy.

	Publications
	Xiong, Z., Qian, W., Suzuki, K., and McNamara, J. (2003) Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration. J. Neurosci. 23: 955-960 Xiong, Z., and McNamara, J. (2002) Fleeting activation of ionotropic glutamate receptors sensitizes cortical neurons to complement attack. Neuron, 36: 363-374 Xiong, Z., and McNamara, J. (2002) Fas(t) balls and Lou Gehrig disease: a clue to selective vulnerability of motor neurons? Neuron, 35: 1011-1013 (preview) Xiong, Z., and Stringer, J. (2001) Effects of postsynaptic GABAB receptor activation on epileptiform activity in hippocampal slices. Neuropharmacology, 40: 131-138 Xiong, Z., Saggau, P., and Stringer, J. (2000) Activity-dependent intracellular acidification correlates with the duration of seizure activity. J. Neurosci., 20: 1290-1296 Xiong, Z., and Stringer, J. (2000) Extracellular pH responses in CA1 and the dentate gyrus during electrical stimulation, seizure discharges, and spreading depression. J. Neurophysiol., 83: 3519-3524 Schweitzer, J., Wang, H., Xiong, Z., and Stringer, J. (2000) pH sensitivity of non-synaptic field bursts in the dentate gyrus. J. Neurophysiol., 84: 927-933 Xiong, Z., and Stringer, J. (2000) Sodium pump activity, not glial spatial buffering, clears potassium after epileptiform activity induced in the dentate gyrus. J. Neurophysiol., 83: 1443-1451 Xiong, Z., and Stringer, J. (1999) Cesium induces spontaneous epileptiform activity without changing extracellular potassium regulation in rat hippocampus. J. Neurophysiol., 82: 3339-3346 Xiong, Z., and Stringer, J. (1997) Effects of felbamate, gabapentin and lamotrigine on seizure parameters and excitability in the rat hippocampus. Epilepsy Res., 27: 187-194