刘江怀实验室
实验室：025-58641556
研究所邮箱：liujianghuai@nicemice.cn
南大邮箱：liujianghuai@nju.edu.cn
研究方向：
实验室近年来开辟的重点方向为开发新型的遗传学工具（synthetic biology及基因改造技术的应用），精准重编细胞功能。得益于我们过去开展的一系列免疫调控研究，目前我们的工具建设首先围绕如何操纵免疫调控开展，并逐步扩展。我们展望，新型的基因操纵工具的建立会在生物医学及农业等领域有广泛应用前景。 实验室目前的主要工作介绍如下。 1.开发新型合成生物学工具及基因组操纵工具，实现功能重编：Synthetic biology是最近兴起的一门学科，其核心是人工构建能够驱动新的生物行为的合成基因工具，并暨此开展基础及应用型研究。譬如，基于CRISPR-转录因子（CRISPR-TF）技术体系（Du 2015），我们进一步着手建立了新型的“基因环路”。该工具可以检测细胞状态的多个参数，并仅仅在细胞满足多参数组合的条件后，精确地对这些特定细胞行使功能重编，诱导抗肿瘤免疫（Wang Y. 2022）。我们也致力于推动其他新型基因改造工具的建立及应用（Zhang G.2022 and Meng Q. – in press）。目前，我们与合作团队设计了新工具开发、小鼠模型中的测试、以及向动物重要经济性状推进等几个层次的持续规划；期望为新兴科学技术的实际转化作有益的尝试。 2.免疫系统的“转向”机制：近十年来肿瘤免疫治疗所取得的重大进展，确立了T细胞在机体对肿瘤的免疫抵抗中的核心地位。由于固有免疫系统与适应性免疫系统的互作是有效免疫应答的重要保障，如何精准刺激固有免疫来增进T细胞介导的抗肿瘤效应是领域内的热点问题。许多研究表明，响应核酸类物质的固有免疫通路的激活，可以通过诱导I型干扰素（IFN-I）及其他一些促炎性介质，有效增强肿瘤抗原特异性T细胞响应。而我们最近的研究发现：IFN-I可以通过一种非经典方式，强烈诱导部分肿瘤相关巨噬细胞（TAM）的免疫抑制性偏向（Tong 2019; Guo 2021），从很大程度上阻碍了抗肿瘤免疫的有效激活。整体看来,对免疫系统中“转向”机制的深入理解将对包括肿瘤、炎症及一系列慢性疾病的研究产生影响。
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1 Song Z†, Zhang G†, Huang S†, Liu Y, Li G, Zhou X, Sun J, Gao P, Chen Y, Huang X, Liu J* and Wang X*. PE-STOP: A versatile tool for installing nonsense substitutions amenable for precise reversion. J Biol Chem 2023, doi: 10.1016/j.jbc.2023.104942.
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2 Li X†, Zhang G†, Huang S†, Liu Y, Tang J, Zhong M, Wang X, Sun W, Yao Y, Ji Q, Wang X, Liu J*, Zhu S*, Huang X*. Development of a versatile nuclease prime editor with upgraded precision. Nat Commun 2023, 14(1):305.
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3 Yang L†, Guo P†, Wang P, Wang W*, and Liu J*.IL-6/ERK signaling pathway participates in type I IFN-programmed, unconventional M2-like macrophage polarization. Sci Rep 2023, 13(1):1827.
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4 Meng Q, Sun H* and Liu J*. Precise somatic genome editing for treatment of inborn errors of immunity. Front Immunol2022, 13:960348.
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5 - Zhang G†, Liu Y†, Huang S†, Qu S, Cheng D, Yao Y, Ji Q, Wang X*, Huang X*, and Liu J*. Enhancement of prime editing via xrRNA motif-joined pegRNA. Nat Commun 2022, 13(1):1856.
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6 - Wang Y†, Zhang G†, Meng Q†, Huang S, Guo P, Leng Q, Sun L, Liu G*, Huang X* and Liu J*. Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors. Nat Commun 2022, 13(1):1454.
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7 - Meng Q†, Yang H†, Zhang G, Ma P, Liu X, Dang L, Li G, Huang X, Wang X*, Liu J* and Leng Q*. CRISPR/Cas12a-assisted rapid identification of beer spoilage bacteria. Innov Food Sci Emerg Technol 2021, 74：102854.
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8 - Gup P†, Yang L†, Zhang M, Zhang Y, Tong Y, Cao Y and Liu J*. A monocyte-orchestrated IFN-I-to-IL-4 cytokine axis instigates pro-tumoral macrophages and thwarts poly(I:C) therapy. J Immunol 2021, 207:408-420.
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9 - Tao T, Sun J, Peng Y, Li Y, Wang P, Chen X, Zhao W, Zheng YY, Wei L, Wang W, Zhou Y, Liu J, Shi YS, Zhu MS. Golgi-resident TRIO regulates membrane trafficking during neurite outgrowth. J Biol Chem 2019, 294(28):10954-10968.
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10 - Tong Y†, Zhou L†, Yang L, Cao Y, Qin FX and Liu J*. Concomitant Type I IFN and M-CSF signaling reprograms monocyte differentiation to drive pro-tumoral arginase production. EBioMedicine 2019, 39:132-44.
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11 - Jiang H†, Shi H†, Sun M, Wang Y, Meng Q, Guo P, Cao Y, Chen J, Gao X, Li E* and Liu J*. PFKFB3-driven macrophage glycolytic metabolism is a crucial component of innate antiviral defense. J Immunol 2016, 197(7):2080-90.
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12 - Dong Z, Huang M, Liu Z, Xie P, Dong Y, Wu X, Qu Z, Shen B, Huang X, Zhang T, Li J, Liu J, Yanase T, Zhou C, Xu Y. Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve. Cell Death Differ 2016, 23(10):1602-14.
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13 - Zhang Y, Wang Y, Zhang C, Wang J, Pan D, Liu J* and Feng F*. Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers. ACS Appl Mater Inter 2016, 8(6):3719-24.
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14 - Du Y†, Meng Q†, Zhang J, Sun M, Shen B, Jiang H, Kang Y, Gao J, Huang X* and Liu J*. Functional annotation of cis-regulatory elements in human cells by dCas9/sgRNA. Cell Res 2015, 25(7):877-80.
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15 - Tong Y†, Li F†, Lu Y, Cao Y, Gao J* and Liu J*, Rapamycin-sensitive mTORC1 signaling is involved in physiological primordial follicle activation in mouse ovary. Mol. Reprod. Dev. 2013, 80:1018–1034.
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16 - HuangFu WC, Qian J, Liu C, Liu J, Lokshin AE, Baker DP, Rui H, and Fuchs, S. Y. Inflammatory signaling compromises cell responses to interferon alpha. Oncogene 2012, 31(2):161-72.
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17 - Jiang H, Lu Y, Yuan L, and Liu J* Regulation of Interleukin-10 Receptor Ubiquitination and Stability by Beta-TrCP-Containing Ubiquitin E3 Ligase. PLoS ONE 2011, 6: e27464.
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18 - Liu J†, Carvalho LP†, Bhattacharya S†, Carbone CJ, Kumar KG, Leu NA, Yau PM, Donald RG, Weiss MJ, Baker DP, McLaughlin KJ, Scott P, Fuchs SY. Mammalian Casein Kinase 1a and Its Leishmanial Ortholog Regulate Stability of IFNAR1 and Type I Interferon Signaling. Mol Cell Biol 2009, 29:6401-12.
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19 - Liu J†, HuangFu WC†, Kumar KG, Qian J, Casey JP, Hamanaka RB, Grigoriadou C, Aldabe R, Diehl JA, Fuchs SY. Virus-induced unfolded protein response attenuates antiviral defenses via phosphorylation-dependent degradation of the type I interferon receptor. Cell Host Microbe 2009, 5:72-83.
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20 - Liu J, Plotnikov A, Banerjee A, Suresh Kumar KG, Ragimbeau J, Marijanovic Z, Baker DP, Pellegrini S, Fuchs SY. Ligand-independent pathway that controls stability of interferon alpha receptor. Biochem Biophys Res Commun 2008, 367:388-93.
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21 - HuangFu WC†, Liu J†, Harty RN, Fuchs SY. Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor. FEBS Lett 2008, 582:3206-10.
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22 - Liu J, Suresh Kumar KG, Yu D, Molton SA, McMahon M, Herlyn M, Thomas-Tikhonenko A, Fuchs SY. Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells. Oncogene 2007, 26:1954-8.
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23 - Liu J*, Fuchs SY. Cross-talk between APC/C and CBP/p300. Cancer Biol Ther 2006, 5:760-2.
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24 - Liu J, Rich CB, Buczek-Thomas JA, Nugent MA, Panchenko MP, Foster JA. Heparin-binding EGF-like growth factor regulates elastin and FGF-2 expression in pulmonary fibroblasts. Am J Physiol Lung Cell Mol Physiol 2003, 285:L1106-15.
| 基金种类 | 基金项目名称 |
|---|---|
| （2021-2026）国家重点研发计划项目 | 奶牛、羊优异新基因资源聚合、创制及评价（课题组长） |
| 国家自然科学基金 31471313 | RLR激活介导的代谢重编对抗病毒固有免疫的调节 |
| 国家自然科学基金 31771574 | 巨噬细胞能量代谢与肝脏损伤后修复的关联及其机制研究 |
| 国家重点研发计划 | 新型基因定点敲入和敲除技术开发（参与，课题骨干） |
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王佩 wangp@nicemice.cn
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庞昕玥
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张益男 zhangyinan@nicemice.cn
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陈平博
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张雨嫣
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张梦凡 zhangmf@nicemice.cn
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郭盼盼 guopp@nicemice.cn
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王亚峰 wangyaf@nicemice.cn
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杨利敏 yanglm@nicemice.cn
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张贵泉 zhanggq@nicemice.cn
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卢轶
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童园园
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孟庆洲
