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He Lab@USTC: 动态发育生物学实验室

利用活细胞成像、细胞及分子生物学工具解析干细胞发育及稳态

 

研究项目

真正理解生物系统,需要掌握特定分子在何时、何地、如何发挥作用的精确信息。过去的研究已经发现了大量调控不同生命过程的基因,但由于缺乏时空动态信息,这些"分子零件"与静态"表型"之间仍存在认知鸿沟。本实验室以模式生物(主要采用黑腹果蝇、小鼠)为研究对象,通过定量方法解析生物信号的时空动态特征,并揭示其在生理与病理状态下的生物学功能。

当前研究项目

干细胞生物学
干细胞在组织再生与肿瘤发生过程中起着核心作用。我们以果蝇肠道干细胞及胃肠道肿瘤为模型,研究干细胞感知与处理内源及外源信号的分子机制,并探索其与癌症发生的内在关联。利用果蝇系统,我们发现肠道干细胞可以通过机械敏感性离子通道Piezo直接响应机械刺激(Nature, 2018),该机制后被其他实验室证明在哺乳动物肠道干细胞中同样存在(Cell Stem Cell, 2023; Science, 2024)。 利用该系统,我们还发现一种新型蛋白质能通过形成独特的线粒体膜微域调控线粒体动力学与线粒体DNA稳态(Nat. Cell Biol., 2025),以及一个KCNK家族的钾离子通道特异性地在成体干细胞和肿瘤细胞中发挥关键作用(JGG,2025)。
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动态过程可视化
“一图胜千言”,活细胞成像技术让我们得以窥探瞬息万变的生命体中各类信号的实时变化。此前,我们成功构建了一种将时间信息编码为颜色比例的转录计时器(eLife, 2019)。该工具助力发现了多个在果蝇肠道干细胞亚群中表达的新基因,其中包括机械敏感通道蛋白Piezo(Nature, 2018)。运用果蝇活体钙离子动态成像技术,我们发现了氨基酸摄取如何通过脑-脂肪组织通讯机制调控脂质代谢(Nat. Commun. 2025)。
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代谢感知的分子机制
生物系统通过与外界持续交换化学代谢物以实现自身发育和稳态。然而动物具体通过何种细胞和分子机制感知这些化合物还未得到有效解析。我们综合活细胞成像和分子技术,发现了果蝇感知特定氨基酸的机制及其下游信号(Nat. Commun. 2005, CMLS, 2024),目前我们正在探索在哺乳动物中是否存在类似机制。
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合成生物学技术
“What I cannot create, I do not understand.“ 我们致力于设计用于发育生物学的分子工具,使人们能够替换、检测并操控动物内的相关信号通路,从而解析生命系统的运行机制。我们此前参与设计了首个合成Notch受体(Dev. Cell,2015),并将其应用于检测动物体内的细胞竞争(PNAS,2017)。该方法被研究哺乳动物的课题组采纳并验证有效(Science,2023)。
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实验室成员

何立, 博士

教授

lihe19@ustc.edu.cn

简历

何昆)

实验室管理

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简历

夏月琴

研究生

sa008191@mail.ustc.edu.cn

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吴尚

研究生

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王欣辉

研究生

--@mail.ustc.edu.cn

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徐璐琳

研究生

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马哲贤

研究生

--@mail.ustc.edu.cn

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张瑞功

研究生

---@mail.ustc.edu.cn

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肖刘艺

研究生

----@mail.ustc.edu.cn

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陈洁琼

研究生

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钟慧娴

研究生

----@mail.ustc.edu.cn

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汪雨千

研究生

----@mail.ustc.edu.cn

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杨昺豪

研究生

----@mail.ustc.edu.cn

简历

实验室往届成员

许桐:医药公司; 刘梦: 蚌埠医科大学;郑晨、夏思桢:政府公务员夏雨晨:复旦大学博士研究生

实验室图片

基本实验技术和方法

实验室论文

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2025

Yue Zhang; Yuchen Xia; Xinhui Wang; Yueqin Xia; Shang Wu; Jianshuang Li; Xuan Guo#; Qinghua Zhou#; Li He#. MISO regulates mitochondrial dynamics and mtDNA homeostasis by establishing membrane subdomains, Nature Cell Biology, Dec. 2025 [pdf]

Muhammad Ahmad; Shang Wu; Shengyao Luo; Wenjia Shi; Xuan Guo; Yuansheng Cao#; Norbert Perrimon#; Li He#. Dietary amino acids promote glucagon-like hormone release to generate global calcium waves in adipose tissues in Drosophila, Nature Communications, Jan. 2025 [pdf]

Chen Zheng; Jiadong Zheng; Xin Wang; Yue Zhang; Xianjue Ma#; Li He#. Two-pore-domain potassium channel Sandman regulates intestinal stem cell homeostasis and tumorigenesis in Drosophila melanogaster, Journal of Genetics and Genomics, May. 2025 [pdf]

Du Kong, Xiaoqin Li, Sihua Zhao, Chenliang Wang, Zixin Cai, Sha Song, Yifan Guo, Xiaoyu Kuang, Xianping Wang, Wenhan Liu, Peng Liu, Xiaowei Guo, Wenyan Xu, Yirong Wang, Bin Zhao, Bin Jin#, Li He#, Xianjue Ma#. Adipose tissue-secreted Spz5 promotes distal tumor progression via Toll-6-mediated Hh pathway activation in Drosophila, EMBO Journal, Jun. 2025 [pdf]

Yuxuan Sun, Boxi Sun, Xiang Cui, Weihua Li, Yue Zhang, Li He, Shutong Nong, Zhengqing Zhu, Jiyang Wu, Dongxiao Li, Xingxiang Li, Shiwu Zhang, Xiangyang Li & Mujun Li. Addressable and perceptible dynamic reprogram of ferromagnetic soft machines, Nature Communications, Mar. 2025 [pdf]

2024

Meng Liu; Li He#. Dietary cysteine and methionine promote peroxisome elevation and fat loss by induction of CG33474 expression in Drosophila adipose tissue, Cellular and Molecular Life Sciences, Dec. 2023 [pdf]

2023

He, L; Perrimon, N. Synthetic Notch receptors and their applications to study cell-cell contacts in vivo, Developmental Cell (News and Views) , Feb, 2023 [pdf]

Yuchen Xia; Yue Zhang; Yuwei Sun; Li He#. CCDC127 regulates lipid droplet homeostasis by enhancing mitochondria-ER contacts, Biochemical and Biophysical Research Communications, Nov. 2023 [pdf]

Song Song, Bomsoo Cho, Alexis T Weiner, Silas Boye Nissen, Irene Ojeda Naharros, Pablo Sanchez Bosch, Kaye Suyama, Yanhui Hu, Li He, Tanya Svinkina, Namrata D Udeshi, Steven A Carr, Norbert Perrimon & Jeffrey D Axelrod. Protein phosphatase 1 regulates core PCP signaling, EMBO reports, Dec. 2023 [pdf]

2020

Ahmad, M, He, L, Perrimon, N. Regulation of insulin and adipokinetic hormone/glucagon production in flies. Wiley Interdiscip Rev Dev Biol. 2019 [pdf]

2019

He, L*#, Binari R, Huang J, Falo-Sanjuan J, Perrimon N#. In vivo study of gene expression with an enhanced dual-color fluorescent transcriptional timer. Elife. 2019 May 29 [pdf]

Hunter, G. L., He, L., Perrimon, N., Charras, G., Giniger, E., and Baum, B. A role for actomyosin contractility in Notch signaling. BMC Biology. November 2019.[pdf]

2018

He, L.*#, Si, G., Huang, J., Samuel, A., and Perrimon, N#. Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel. Nature, 07 Feb. 2018. [pdf]

Parasram, K, Bernardon, N, Hammoud, M, Chang, H, He, L, Perrimon, N, Karpowicz, P. Intestinal Stem Cells Exhibit Conditional Circadian Clock Function. Stem Cell Reports. 2018 Nov 13.[pdf]

He, L., Ahmad, M., Perrimon, N., Mechanosensitive channels and their functions in stem cell differentiation. Experimental Cell Research [pdf]

2017

He, L., Huang, J., and Perrimon, N. (2017) Development of an optimized synthetic Notch receptor as an in vivo cell-cell contact sensor. Proceedings of the National Academy of Sciences 5467-5472[pdf]

Xu, C., Luo, J., He, L., Montell, C., and Perrimon, N. (2017) Oxidative stress induces stem cell proliferation via TRPA1/RyR-mediated Ca2+ signaling in the Drosophila midgut. eLife. [pdf]

2016

Hunter, G. L., Hadjivasiliou, Z., Bonin, H., He, L., Perrimon, N., harras, G., and Baum, B. (2016) Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning. Development 2305-2310. [pdf]

2015

Prasad, M., Wang, X., He, L., Cai, D., and Montell, D. J. (2015) Border cell migration: a model system for live imaging and genetic analysis of collective cell movement. Drosophila Oogenesis. Methods in Molecular Biology, vol 1328.[pdf]

Chen, C.-L., Hu, Y., Udeshi, N. D., Lau, T. Y., Wirtz-Peitz, F., He, L., Ting, A. Y., Carr, S. A., and Perrimon, N. (2015) Proteomic mapping in live Drosophila tissues using an engineered ascorbate peroxidase. Proceedings of the National Academy of Sciences 112.[pdf]

Gordon, W. R., Zimmerman, B., He, L., Miles, L. J., Huang, J., Tiyanont, K., McArthur, D. G., Aster, J. C., Perrimon, N., Loparo, J. J., and Blacklow, S. C. (2015) Mechanical allostery: evidence for a force requirement in the proteolytic activation of Notch. Developmental Cell.[pdf]

2014

Koride, S., He, L., Xiong, L.-P., Lan, G., Montell, D. J., and Sun, S. X. (2014) Mechanochemical regulation of oscillatory follicle cell dynamics in the developing Drosophila egg chamber. Molecular Biology of the Cell.[pdf]

Cai, D., Chen, S.-C., Prasad, M., He, L., Wang, X., Choesmel-Cadamuro, V., Sawyer, J. K., Danuser, G., and Montell, D. J. (2014) Mechanical feedback through Ecadherin promotes direction sensing during collective cell migration. Cell [pdf]

2012

He, L. and Montell, D. (2012) A cellular sense of touch. Nature Cell Biology (News and Views) 14, 902-903.[pdf]

2011

He, L., Wang, X., and Montell, D. J. (2011) Shining light on Drosophila oogenesis: live imaging of egg development. Current Opinion in Genetics & Development 612-619. [pdf]

Sawyer, J. K., Choi, W.*, Jung, K.-C.*, He, L.*, Harris, N. J., and Peifer, M. (2011) A contractile actomyosin network linked to adherens junctions by Canoe/afadin helps drive convergent extension. Molecular Biology of the Cell 22, 2491-2508. [pdf]

Wu, Y. I., Wang, X., He, L., Montell, D., and Hahn, K. M. (2011) Spatiotemporal control of small GTPases with light using the LOV domain. Methods in Enzymology 497, 393-407. [pdf]

Prasad, M., Wang, X., He, L., and Montell, D. J. (2011) Border cell migration: a model system for live imaging and genetic analysis of collective cell movement. Cell Migration. Methods in Molecular Biology (Methods and Protocols) [pdf]

2010

He, L.*, Wang, X.*, Tang, H. L., and Montell, D. J. (2010) Tissue elongation requires oscillating contractions of a basal actomyosin network. Nature Cell Biology 12, 1133-1142 [pdf]

Wang, X.*, He, L.*, Wu, Y. I., Hahn, K. M., and Montell, D. J. (2010) Light mediated activation reveals a key role for Rac in collective guidance of cell movement in vivo. Nature Cell Biology 12, 591-597 [pdf]

 

实验室新闻

诚聘实验室成员 博士后研究员:我们诚邀对以下研究方向感兴趣的候选人加入——线粒体生物学、功能性活细胞成像、肠道干细胞、细胞力学。请将个人简历及简要研究意向说明发送至邮箱(lihe19@ustc.edu.cn)。

研究生:我们正在寻找对生物系统体内动态特性的可视化与调控研究充满热情、积极主动的科研人才。

本科生:本科生将获得独立研究课题,学习分子生物学、果蝇遗传学及活细胞成像等技术。

请将个人简历发送至邮箱(lihe19@ustc.edu.cn)。



联系方式:

Email: lihe19@ustc.edu.cn

Phone: 086-0551-63606857

Mailing:

Li He, Ph.D.

Rm 107, Life Science Bldg. USTC
#443 Huangshan Street, Hefei, Anhui, 230027 P.R.China.

 

何立

中国科学技术大学西校区 生命科学楼 107

安徽省 合肥市 蜀山区 黄山路 443

邮编 230027

Our Lab Location: