戈鹉平

大脑的代谢

大脑内主要有八大细胞类型：神经元、四类胶质细胞和三类血管细胞 。不同种类的细胞纵横交错形成一个复杂的“生态”系统。代谢物 (metabolite)，是代谢的中间产物或者代谢的终产物，特指分子量小于900道尔顿以下的小分子。迄今发现，一个细胞已知的代谢物有2000–6000种，包含20种常见氨基酸及其众多衍生物。那么，大脑中的八大类细胞如何相互供给代谢物来行驶其功能？在过去几十年中因受到技术限制，针对这个基本问题，在大脑中研究比较清楚的代谢物屈指可数（如谷氨酸、谷氨酰胺、乳酸）。

我们实验室试图回答这几个问题：

(1) 体内各器官产生的各种代谢物，进入血液循环系统后，哪些被大脑吸收并消耗？ 它们为哪一类特定脑细胞所利用？如何利用？

(2) 八类细胞各自产生哪些特定的代谢物？这些代谢物如何在细胞间传递并被利用？它们如何参与各种脑细胞的生长、发育、活动并影响脑的功能？

(3) 如何干预特定的代谢物，来实现脑相关疾病（比如老年痴呆或者脑肿瘤）的早期诊断、分型或者治疗？

“神经元－胶质细胞－血管网络”构建、坍塌与修复

脑内八大类细胞交错形成一个非常复杂而精美的“神经元－胶质细胞－血管网络”（Neurovascular unit/network）。我们非常好奇这个网络在发育中是如何形成？通过各种颜色的荧光蛋白标记脑中特定细胞类型来实现多类细胞同时成像，并在活体下直接观察脑微血管循环如何和神经元，神经胶质细胞构建成一个完整的网络。另外，脑在病理情况下（比如卒中），整个网络是如何坍塌的？是否可以部分修复其功能？我们期望通过对这些问题的研究来更好的理解大脑发育或者为大脑修复提供新的治疗思路与策略。

神经胶质细胞的发育和功能

大脑中神经元负责信息的产生、处理和传输。神经胶质细胞为神经元提供支持、保护和营养等作用。 脑外很多器官也存在大量的神经胶质细胞（比如心脏的胶质细胞），但我们对其功能大多一无所知。 我们利用各种新的技术手段探讨外周各器官的胶质细胞的起源、发育、分化及其功能。

技术与方法的创新

本实验室期望通过质谱、细胞活体成像、全器官透明、全器官扫描成像、电生理技术、遗传学、分子生物学及生物信息分析等手段，来探讨上述一系列极具挑战的科学问题。 一个领域的发展和突破，往往受限于技术，开创全新技术、方法和计算手段并引入到上述研究也是我们实验室的重点。

我们和众多实验室合作，已经开发的和正在建立的新技术／方法包括：

1. SIMPLE （利用磁力可逆控制脑微血管循环）

2. CARVE: 肿瘤的动脉-静脉血液组分比对分析肿瘤代谢

3. 动静脉血液组学比对介导的疾病诊断 （更新中）

4. PEGASOS全身透明成像技术 (协助赵瑚教授实验室)

所有发表的文章

https://pubmed.ncbi.nlm.nih.gov/?term=%22woo-ping+ge%22+OR+%22wooping+ge%22&sort=date&size=100

实验室相关工作报道：

Cell Reports | 物以类聚： 癌细胞有选择性地和特定类型的非癌细胞“交流”

https://wemp.app/posts/6ec76017-baf4-4ec8-b7ab-3b264c1f03ac

Researcher wins first Dan Adams Award grant for brain study

https://newsarchive.heart.org/researcher-wins-first-dan-adams-award-grant-for-brain-study/

2007   国际人类前沿科学计划长期资助(LTF)奖

2007   2006中国基础研究十大新闻

2008   中国百篇优秀博士论文

2009   上海自然科学奖一等奖 (第二完成人)

2010   国家自然科学奖二等奖 (第二完成人)

2011   美国国立卫生研究院迈向独立奖 (K99/R00)

2017   美国心脏协会鲍尔－丹.亚当斯创新思维奖(唯一获奖人)

1. Ai D, Qiu B, Chen XJ, Li F, Yao D, Mi H, Li JL, Zhou B, Zuo J, Wang Y, Ge WP, Sun W. Inhibition of microglial Slc2a5 attenuates ischemic brain injury. Metabolism. 2025 Nov 6;175:156429. Epub ahead of print. PMID: 41205649.

2. Yue C, Wang N, Zhai H, Yuan Z, Cui Y, Quan J, Zhou Y, Fan X, Wang H, Wu Z, Mi H, Ge WP, Li Y, Wang X, Luo M. Adenosine signalling drives antidepressant actions of ketamine and ECT. Nature. 2025 Nov 5. Epub ahead of print. PMID: 41193806.

3. Li JL, Bi Z, Chen XJ, Ming T, Qiu B, Li F, Feng Z, Ai D, Zhang T, Wang J, Lin S, Lu Y, Wang Z, Huang J, Zhao F, Zhao H, Wang Y, Sun W, Ge WP. rAAV-miniBEND: A targeted vector for brain endothelial cell gene delivery and cerebrovascular malformation modeling.  Nature Biomedical Engineering. 2025 Oct 29. Epub ahead of print. PMID: 41162685.

4. He W, Gao S, Du L, Han T, Yao D, Wu H, Li Q, Li F, Ge WP, Wang Y. Cisternostomy Facilitates Clearance of Metabolic Waste from Cerebrospinal Fluid in Patients with Severe Brain Injury. Aging Dis. 2025 Oct 27.

5. Zhang Z, Pilch J, Lundt S, Zhang N, Chang Y, Singer T, Śladowski D, Hu XL, Zheng L, Ge WP, Zhang H, Li DP, Han X, Ploski R, Ding S. A sensory and motor neuropathy caused by a genetic variant of NAMPT. Sci Adv. 2025 Sep 26;11(39):eadx2407.

6. Gao X, Chen X, Li JL, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J, Yi Y, Zhang S, Shi Y, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu YM, Yang SB, Adams RF, Lindner V, Huang F, Wu LJ, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Korbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Sun W, Bachoo RM, Ge WP. Reduction of neuronal activity mediated by blood-vessel regression in the brain. Nature Communications. 2025 Jul 1;16(1):5840.

7. Wang Y, Zhou L, Wang N, Qiu B, Yao D, Yu J, Li T, He M, Xie Y, Yu X, Bi Z, Sun X, Ji X, Li Z, Mo D, Ge WP. Comprehensive characterization of metabolic consumption and production by the human brain. Neuron. 2025;113(11):1708-1722.

8. Ai D, Ming T, Li X, Wang S, Bi Z, Zuo J, Cheng Z, Sun W, Xie M, Li F, Wang X, Qi X, Luan G, Ge WP, Guan Y. Transcriptomic Profiling Unveils EDN3+ Meningeal Fibroblasts as Key Players in Sturge-Weber Syndrome Pathogenesis. Adv Sci (Weinh). 2025 Feb 8:e2408888.

9. Cheng X, Zhao M, Chen L, Huang C, Xu Q, Shao J, Wang HT, Zhang Y, Li X, Xu X, Yao XP, Lin KJ, Xue H, Wang H, Chen Q, Zhu YC, Zhou JW, Ge WP, Zhu SJ, Liu JY, Chen WJ, Xiong ZQ. Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1. Neuron. 2024 Sep 25;112(18):3126-3142.

10. Zhang TT, Ai DS, Wei PL, Xu Y, Bi ZY, Ma FF, Li FZ, Chen XJ, Zhang ZH, Zou XX, Guo ZP, Zhao Y, Li JL, Ye M, Feng ZY, Zhang XS, Zheng LJ, Yu J, Li CL, Tu TQ, Zeng HK, Lei JF, Zhang HQ, Hong T, Zhang L, Luo BY, Li Z, Xing C, Jia CX, Li LJ, Sun WZ, Ge WP.  The subcommissural organ regulates brain development via secreted peptides.  Nat Neurosci. 2024 Jun;27(6):1103-1115.

11. Yi Y, Li Y, Zhang S, Men Y, Wang Y, Jing D, Ding J, Zhu Q, Chen Z, Chen X, Li JL, Wang Y, Wang J, Peng H, Zhang L, Luo W, Feng JQ, He Y, Ge WP, Zhao H. Mapping of individual sensory nerve axons from digits to spinal cord with the transparent embedding solvent system.  Cell Research. 2024; 34(2): 124-139.

12. Zhang D, Ruan J, Peng S, Li J, Hu X, Zhang Y, Zhang T, Ge Y, Zhu Z, Xiao X, Zhu Y, Li X, Li T, Zhou L, Gao Q, Zheng G, Zhao B, Li X, Zhu Y, Wu J, Li W, Zhao J, Ge WP, Xu T, Jia JM. Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling. Nature Neuroscience. 2024; 27(2): 232-248.

13. Ren J, Huang Y, Ren Y, Tu T, Qiu B, Ai D, Bi Z, Bai X, Li F, Li JL, Chen XJ, Feng Z, Guo Z, Lei J, Tian A, Cui Z, Lindner V, Adams RH, Wang Y, Zhao F, Körbelin J, Sun W, Wang Y, Zhang H, Hong T, Ge WP. Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations. Brain. 2023; 146(9): 3634-3647.

14. Hu Y, Cao K, Wang F, Wu W, Mai W, Qiu L, Luo Y, Ge WP, Sun B, Shi L, Zhu J, Zhang J, Wu Z, Xie Y, Duan S, Gao Z. Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity. Nature Metabolism. 2022; 4(12): 1756-1774.

15. Gao X, Li JL, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J, Yi Y, Zhang S, Shi Y, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco DB, Lu YM, Yang SB, Adams RF, Lindner V, Huang F, Wu LJ, Zheng H, Han F, Hippenmeyer S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Korbelin J, Trepel M, Lu H, Zhou BO, Zhao H, Sun W, Bachoo RM, Ge WP . Reduction of neuronal activity mediated by blood-vessel regression in the brain. BioRxiv. (9/15/2020)

16.  Xiong N, Gao X, Zhao H, Cai F, Zhang FC, Yuan Y, Liu W, He F, Zacharias LG, Lin H, Vu HS, Xing C, Yao DX, Chen F, Luo B, Sun W, DeBerardinis DJ, Hao Xu H, Ge WP. Using arterial-venous analysis to characterize cancer metabolic consumption in patients. Nature Communications. 2020; 11(1): 3169.  

17. 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.

18. Huang G, Zhao T, Wang C, Nham K, Xiong YH, 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.  2020; 4: 314-324

19. 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.

20. 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 Research. 2018; 28: 803-818.  

21. 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: e25730.

22. 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. Control of cerebral ischemia with magnetic nanoparticles. Nature Methods. 2016; 14(2):160-166.  

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

24. 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. An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging. Nature Communications. 2014; 5: 3626.

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

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

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

28. Ge WP, Zhou W, Luo Q, Jan LY, Jan YN Jan. Dividing glial cells maintain differentiated properties including complex morphology and functional synapses. PNAS. 2009; 106(1): 328-333.                

29. Chung HJ, Ge WP, Qian X, Wiser O, Jan YN, Jan LY. G protein-activated inwardly rectifying potassium channels mediate depotentiation of long-term potentiation. PNAS. 2009; 106(2): 635-640.

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

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

32. Yang Y, Ge WP, Chen Y, Zhang Z, Shen W, Wu C, Poo M, Duan S. Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. PNAS. 2003; 100(25):15194-15199.

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