科学研究

Principal Investigators

Woo-Ping Ge Ph.D.

E-mail: woopingge@@cibr.ac.cn(remove one@ when use it)

Phone:

Lab Homepage: https://www.woopinglab.org/

Education

2000    B.S., Biochemistry,East China Normal University, China

2005    Ph.D., Neurobiology Institute of Neuroscience, Chinese Academy of Sciences, China


Professional Experience

2006-2011            Post-doc, Developmental Neurobiology, University of California, San Francisco/HHMI, USA

2005-2006            Research Associate, Lab of Shumin Duan, Institute of Neuroscience, Chinese Academy of Sciences

2006                      Research Associate, Lab of Zuoren Wang, Institute of Neuroscience, Chinese Academy of Sciences

2006                      Visiting Scholar, Lab of Chi-Keung Chan, Institute of Physics Academia Sinica, Taiwan

2011-2013            Associate specialist, Lab of Lily Jan, University of California, San Francisco/HHMI

2013.9-2019.3       Assistant Professor (tenure-track), Children's Research Institute, Department of Pediatrics 

                              Department of Neuroscience, Department of Neurology & Neurotherapeutics

                              University of Texas Southwestern Medical Center

2019/12-now        Associate Investigator, Chinese Institute for Brain Research, Beijing


Honors-Awards

2007    Human Frontier Science Program Long-term Fellowship Award 

2007    China's Top 10 Advances in Basic Research in 2006 

2008    100 Excellent Ph.D. theses of China

2010    The State Natural Science Award (2nd Contributor)

2011    NINDS Pathway to Independence Award (K99/R00)

2017    Bugher-AHA Dan Adams Thinking Outside the Box Award

            (The Henrietta B. and Frederick H. Bugher Foundation)


Research Description

Neurological disorders, such as stroke and brain tumors, affect up to one billion people worldwide. Finding new treatments and understanding how these neurological disorders develop requires a better understanding of the complex interactions that occur in the brain. Our lab’s primary interest is studying interactions between brain vasculature (blood vessels) and the nervous system (glial cells and neurons). By combining electrophysiology and in vivo imaging with genetic methods, we hope to determine how the brain builds the gliovascular and neurovascular network during development and how this network can be damaged as a result of a stroke and then repaired.

Current treatment methods for patients with gliomas are hampered by a poor understanding of underlying biology. Glial cells are critical for brain metabolism, neuronal protection, and cell-cell communication. As a group with long-term experience in studying the function and development of astrocytes and NG2 glia, we are interested in how gliomas interact with adjacent normal glial cells and how glial cells create a microenvironment that influences glioma cell survival, proliferation, and invasion.

Neuron/Glia-Pericyte Interactions

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Although pericytes are located along vessels in both the central nervous system and other organs, astrocytic endfeet cover only the vasculature in the central nervous system. It remains unclear whether there are subtypes of pericytes in blood vessels and, if so, what their functions are in the brain. There is also little information available about how different subtypes of pericytes interact with glial cells or neurons in the brain.To answer these questions, we will introduce techniques including electrophysiology and in vivo imaging into the study of brain pericytes. The goal is to isolate pericytes from several sources (arterioles, precapillaries, capillaries, postcapillaries and venules) to characterize the molecular and cellular profile of pericytes from these different locations. We have already established an electrophysiological technique to record individual pericytes within different segments of blood vessels in acutely isolated brain slices.

Formation of Gliovascular Interface

Glial cells constitute approximately half of the cells in the human brain. As the largest population of glial cells, astrocytes are crucial for the survival and function of neurons. Together with brain vasculature, astrocytic endfeet form an intricate structure called the gliovascular interface. This interface is critical for the transport of glucose from the blood to neurons, the regulation of cerebral blood flow and the maintenance of the blood-brain barrier. Detachment of astrocytic endfeet from the vascular membrane is responsible for brain edema and results in neurodegeneration. Restoring this function after stroke is critical to improving functional brain recovery in patients.How the gliovascular interface forms and develops is unclear. We are studying the cellular and molecular mechanisms for interactions between brain vasculature and astrocytes with genetic manipulation and time-lapse slice or in vivo imaging.

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Glia-Glioma Interactions 

The brain consists of multiple cell types that form a complex neuron-glia-blood vasculature network. During glioma (brain tumor) development, tumor cells infiltrate normal brain tissue and interact with adjacent stromal cells in this network . The network provides glioma cells with an appropriate environment for colonization, growth and infiltration. However, the role of normal glial cells, which constitute 50 percent of cells in the human brain and are critical for a number of functions (brain metabolism, neuronal protection and cell-cell communication), in glioma progression is poorly understood. Improving our understanding of glia-glioma interactions and discovering the underlying mechanisms are critical for the diagnosis, prognosis and treatment of pediatric glioma and necessary to identify new therapeutic targets.

We are currently investigating if and how different types of glial cells, especially astrocytes, create a microenvironment that promotes glioma cell survival, proliferation and invasion. This includes characterization of the fate and potential functional alterations of astrocytes adjacent to gliomas in vivo. We will perform longitudinal time-lapse imaging to characterize astrocyte properties (survival, proliferation and progeny) within and close to gliomas at different developmental stages. This will provide researchers with a functional paradigm for glioma growth from its initiation through the late stage.

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Development of New Tools

We are interested in establishing new tools and methods to study how gliovascular units behave during strokes and in brain tumor in vivo.Currently, it is difficult for researchers to take advantage of advanced live-imaging technologies in stroke studies, particularly in the developing mouse brain, due to vascular surgical challenges. We have developed a novel approach to induce focal ischemia with precise control of infarct size and occlusion duration in mice at any postnatal age (Jie et al., Nature Methods, 2016). We achieved the occlusion, which is reversible, via micromagnet-mediated aggregation of magnetic nanoparticles within a blood vessel. In combination with longitudinal live imaging, we will investigate underlying mechanisms of disruption and repair of neurovascular units in vivo under ischemic stroke.

Publications

1.Gao X, Zhang Z, Mashimo T, Shen B, Nyagilo J, Wang H, Wang Y, Liu Z, Mulgaonkar A, Hu XL, Piccirillo SGM, Eskiocak U, Davé DP, Qin S, Yang Y, Sun X, Fu YX, Zong H, Sun W, Bachoo RM, Ge WP. Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles. Cell Reports. 2020;30(8):2489-2500.e5.PDF

2.Li W, Chaudhari K, Shetty R, Winters A, Gao X, Hu Z, Ge WP, Sumien N, Forster M, Liu R, Shao-Hua Yang SH. Metformin Alters Locomotor and Cognitive Function and Brain Metabolism in Normoglycemic Mice.  Aging and Disease. (2019);10(5):949-963. doi: 10.14336/AD.2019.0120.

3.Luo W, Yi Y, Jing D, Zhang S, Men Y, Ge WP, Zhao H.  Investigation of Postnatal Craniofacial Bone Development with Tissue Clearing-Based Three-Dimensional Imaging. Stem Cells Dev. (2019) 28(19):1310-1321. doi: 10.1089/scd.2019.0104. 

4.Huang G, Zhao T, Wang C, Nham K, Xiong Y, Gao X, Wang Y, Hao G, Ge WP, Sun X, Sumer BD, Gao J. PET imaging of occult tumours by temporal integration of tumour-acidosis signals from pH-sensitive 64Cu-labelled polymers. Nature Biomedical Engineering  (2019). doi: 10.1038/s41551-019-0416-1.

5.Huang L, Chambliss KL, Gao X, Yuhanna IS, Behling-Kelly E, Bergaya S, Ahmed M, Michaely P, Luby-Phelps K, Darehshouri A, Xu L, Fisher EA, Ge WP, Mineo C, Shaul PW.  SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis. Nature. (2019);569(7757):565-569.

6.Xin Y, Gao X, Liu L, Ge WP, Jain MK, Cai H.Evaluation of L-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer.  Mol Imaging Biol. (2019). doi: 10.1007/s11307-019-01327-4.

7.Yi Y, Men Y, Jing D, Luo W, Zhang S, Feng JQ, Liu J, Ge WP, Wang J, Zhao H. 3-dimensional visualization of implant-tissue interface with the polyethylene glycol associated solvent system tissue clearing method.  Cell Prolif. (2019):e12578. doi: 10.1111/cpr.12578.

8.Jia JM, Peng C, Wang Y, Zheng J, Ge WP. Control of occlusion of middle cerebral artery in perinatal and neonatal mice with magnetic force. Mol Brain. (2018);11(1):47. doi: 10.1186/s13041-018-0389-0.

9.Jing D, Zhang S, Luo W, Gao X, Men Y, Ma C, Liu X, Yi Y, Bugde A, Zhou BO, Zhao Z, Yuan Q, Feng JQ, Gao L, Ge WP, Zhao H.Tissue clearing of both hard and soft tissue organs with the PEGASOS method. Cell Res. (2018) May 29. doi: 10.1038/s41422-018-0049-z. PDF

10.Celen C, Chuang JC, Luo X, Nijem N, Walker AK, Chen F, Zhang S, Chung AS, Nguyen LH, Nassour I, Budhipramono A, Sun X, Bok LA, McEntagart M, Gevers EF, Birnbaum SG, Eisch AJ, Powell CM, Ge WP, Santen GW, Chahrour M, Zhu H. Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment. Elife. (2017) 6. pii: e25730. doi: 10.7554/eLife.25730.

11.Peng C, Gao X, Xu J., Du B, Ning X, Tang S, Bachoo RM, Yu M, Ge WP*, Zheng J*, Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles. Nano Res. (2017). 10(4), 1366-1376.

12.Ge WP, Jia JM (2016) Local production of astrocytes in the cerebral cortex. Neuroscience 323:3-9.

13.Jia JM, Chowdary PD, Gao X, Ci B, Li W, Mulgaonkar A, Plautz EJ, Hassan G, Kumar A, Stowe AM, Yang SH, Zhou W, Sun X, Cui B*, Ge WP* (2016) Control of cerebral ischemia with magnetic nanoparticles. Nat Methods. 14(2):160-166. doi: 10.1038/nmeth.4105. PDF

14.Shen Y, Ge WP, Li Y, Hirano A, Lee HY, Rohlmann A, Missler M, Tsien RW, Jan LY, Fu YH, Ptáček LJ (2015) Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis. Proc Natl Acad Sci U S A. 112(10):2935-2941.

15.Yu D, Gustafson WC, Han C, Lafaye C, Noirclerc-Savoye M, Ge WP, Thayer DA, Huang H, Kornberg TB, Royant A, Jan LY, Jan YN, Weiss WA, Shu X. (2014) An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging. Nat Commun. 5:3626.

16.Ge WP, Miyawaki A, Gage FH, Jan YN, Jan LY. (2012) Local generation of glia is a major astrocyte source in postnatal cortex. Nature 484(7394); 376-380.PDF

17.Ultanir SK, Hertz NT, Li G, Ge WP, Burlingame AL, Pleasure SJ, Shokat KM, Jan LY, Jan YN. (2012) Chemical genetic identification of NDR1/2 kinase substrates AAK1 and Rabin8 uncovers their roles in dendrite arborization and spine development. Neuron 73(6): 1127-1142.

18.Lee HY, Ge WP, Huang W, He Y, Wang GX, Rowson-Baldwin A, Smith SJ, Jan YN, Jan LY. (2011) Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein. Neuron 72(4); 630-642

19.Ge WP, Zhou W, Luo Q, Jan LY, Jan YN Jan. (2009). Dividing glial cells maintain differentiated properties including complex morphology and functional synapses. Proc Natl Acad Sci U S A. 106(1):328-333.PDF

20.Chung HJ*, Ge WP*, Qian X, Wiser O, Jan YN, Jan LY. (2009). G protein-activated inwardly rectifying potassium channels mediate depotentiation of long-term potentiation. Proc Natl Acad Sci U S A. 106(2):635-640.

21.Zhou W, Ge WP*, Zeng S, Duan S, Luo Q. (2007). Identification and two-photon imaging of oligodendrocyte in CA1 region of hippocampal slices. Biochem Biophys Res Commun. 352(3):598-602.

22.Zhang W, Ge WP, Wang ZA. (2007). A toolbox for light control of Drosophila behaviors through Channelrhodopsin mediated photoactivation of targeted neurons. Eur J Neurosci. 26(9):2405-2416.

23.Ge WP, Duan S. (2007). Persistent enhancement of neuron-glia signaling mediated by increased extracellular Kaccompanying long-term synaptic potentiation. J Neurophysiol. 97(3):2564-2569. 

24.Ge WP*, Yang XJ*, Zhang Z, Wang HK, Shen W, Deng QD, Duan S. (2006). Long-term potentiation of neuron-glia synapses mediated by Ca2+-permeable AMPA receptors. Science. 312(5779):1533-1537.PDF

25.Jin W, Ge WP, Xu J, Cao M, Peng L, Yung W, Liao D, Duan S, Zhang M, Xia J. (2006). Lipid binding regulates synaptic targeting of PICK1, AMPA receptor trafficking, and synaptic plasticity. J Neurosci. 2006:26(9):2380-2390. 

26.Yang Y*, Ge WP*, Chen Y, Zhang Z, Shen W, Wu C, Poo M, Duan S. (2003). Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proc Natl Acad Sci U S A. 100(25):15194-15199.

27.Zhang JM, Wang HK, Ye CQ, Ge WP, Chen Y, Jiang ZL, Wu CP, Poo MM, Duan S. (2003). ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron. 40(5):971-982.