研究领域
程序性细胞死亡（Programmed cell death）在多细胞生物生长发育，维持内环境稳定和平衡方面发挥着至关重要的作用。程序性细胞死亡的异常往往会导致癌症等一系列的疾病。本实验室将综合细胞生物学、生物化学、分子生物学、生物信息学和小鼠模型等实验技术围绕程序性细胞死亡及其相关的人类疾病开展研究。具体研究方向如下：
1．铁坏死（ferroptosis）的分子机制
铁坏死最初是由人工合成的小分子化合物erastin诱导的一种独特的细胞死亡形式。分子机制上，不同于细胞凋亡和RIPK3依赖的程序性细胞坏死，铁坏死依赖于细胞内的铁离子和活性氧（reactive oxygen species, ROS）。研究发现，erastin抑制细胞膜上的光氨酸/谷氨酸转运蛋白的活性，进而抑制细胞对光氨酸的吸收，致使细胞无法合成谷胱甘肽，进而导致细胞无法维持氧化还原水平的平衡，最终导致细胞死亡。尽管铁坏死与很多疾病都密切相关，但是我们对铁坏死分子机制和生物学功能还知之甚少。我们将主要集中于铁坏死的分子机制方面的研究，同时利用对铁坏死分子机制及其在疾病发生中的研究，探索相关疾病的新的治疗方案。
2．自嗜对程序性细胞死亡的调控
细胞自噬是一种进化上非常保守的降解途径。自噬作用可帮助细胞清除废物和异物，抑制细胞死亡的发生，促进细胞存活。但是，在某些情况下，自嗜也能够促进程序性细胞死亡的进程，我们最近发现自嗜能够通过调节铁代谢来促进铁坏死，但其机制还非常不清楚。我们将对这些问题进一步深入研究。
3．肿瘤细胞代谢调控
肿瘤细胞需要获得更多地营养来满足其细胞旺盛的分裂和生长能力，然而肿瘤细胞往往面临的营养缺乏的肿瘤微环境。肿瘤细胞通过改变其代谢途径来满足其高速分裂和生长所需要的营养和能量。我们主要关注肿瘤细胞氨基酸代谢的调控机制。
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Guidelines for the use and interpretation of assays for monitoring autophagy Klionsky DJ# et al, Gao M 期刊名称 Autophagy
LKB1-AMPK axis negatively regulates ferroptosis by inhibiting fatty acid synthesis Changzhi Li, Xuan Dong, Wenjing Du, Xin Shi, Kangjie Chen, Wei Zhang# and Minghui Gao# 2020.09.03 期刊名称 Signal Transduction and Targeted Therapy 期卷 (2020)5:187
Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling. Wu J*, Minikes AM*, Gao M, Bian H, Li Y, Stockwell BR, Chen ZN Jiang X. 2019 Aug 期刊名称 Nature 期卷 572(7769):402-406.
Role of Mitochondria in Ferroptosis Gao M*#, Yi J* Zhu J, Minikes A, Monian P, Thompson C, and Jiang X# 2019 期刊名称 Molecular Cell 期卷 73, 1–10, January 17, 2019
Unc-51-like kinase (ULK) complex-independent autophagy induced by hypoxia Feng Y*, Kang HH*, Wong PM, Gao M, Wang P, Jiang X 2018 期刊名称 Protein Cell 期卷 2018 Oct 29. doi: 10.1007/s13238-018-0584-x
To Eat or Not to Eat – The Metabolic Flavor of Ferroptosis. Gao M#, Jiang X#. 期刊名称 Current Opinion in Cell Biology 期卷 51:58-64
The NLR protein SUMM2 senses the disruption of an immune signaling MAP kinase cascade via CRCK3 Zhang Z, Liu Y, Huang H, Gao M, Wu D, Kong Q, Zhang Y 期刊名称 EMBO Rep. 期卷 18(2):292-302
Ferroptosis is an autophagic cell death process Gao M#, Monian P, Pan Q, Wei Zhang W, Xiang J, Jiang X# 期刊名称 Cell Research 期卷 26(9):1021-32
Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth Kim SE, Zhang L, Ma K, Riegman M, Chen F, Ingold I, Conrad M, Turker MZ, Gao M, Jiang X, Monette S, Pauliah M, Gonen M, Zanzonico P, Quinn T, Wiesner U,Bradbury MS, Overholtzer M. 期刊名称 Nat Nanotechnol 期卷 11(11):977-985
Metabolism and Iron Signaling in Ferroptotic Cell Death Gao M, Monian P, Jiang X. 期刊名称 Oncotarget 期卷 6(34):35145-6.
Glutaminolysis and Transferrin Regulate Ferroptosis. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X 期刊名称 Molecular Cell 期卷 59(2):298-308
Regulation of SOBIR1 accumulation and activation of defense responses in bir1-1 by specific components of ER quality control Sun T, Zhang Q, Gao M, Zhang Y. 期刊名称 The Plant Journal 期卷 77 (5):748-56
The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates immunity mediated by a mitogen-activated protein kinase kinase kinase in Arabidopsis. Kong Q*, Qu N*, Gao M, Zhang Z, Ding X, Yang F, Li Y, Dong OX, Chen S, Li X, Zhang Y. 期刊名称 Plant Cell 期卷 (5):2225-36
Disruption of PAMP-induced MAP kinase cascade by a Pseudomonas syringae effector activates plant immunity mediated by the NB-LRR protein SUMM2. Zhang Z, Wu Y, Gao M, Zhang J, Kong Q, Liu Y, Ba H, Zhou J, Zhang Y 期刊名称 Cell Host Microbe. 期卷 (3):253-63
Control of salicylic acid synthesis and systemic acquired resistance by two members of a plant-specific family of transcription factors Zhang, Y., Xu, S., Ding, P., Wang, D., Cheng, Y., He, J., Gao, M., Xu, F., Li, Y., Zhu, Z., Li, X., and Zhang, Y 期刊名称 Proceedings of the National Academy of Sciences 期卷 107(42):18220-18225
Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a Pseudomonas.syringae.effector. Zhang J, Li W, Xiang T, Liu Z, Laluk K, Ding X, Zou Y, Gao M, Zhang X, Chen S, Mengiste T, Zhang Y, Zhou JM 期刊名称 Cell Host &Microbe 期卷 (4):290-301
Two Prp19-Like U-Box Proteins in the MOS4-Associated Complex Play Redundant Roles in Plant Innate Immunity
Monaghan J, Xu F, Gao M, Zhao Q, Palma K, Long C, Chen S, Zhang Y, Li X. 期刊名称 PLoS Pathog 期卷 5(7): e1000526
Regulation of cell death and innate immunity by two receptor-like kinases in Arabidopsis. Gao M, Wang X, Wang D, Xu F, Ding X, Zhang Z, Bi D, Cheng YT, Chen S, Li X, Zhang Y 期刊名称 Cell Host & Microbe 期卷 6: 34-44
MEKK1, MKK1/MKK2 and MPK4 function together in a mitogen-activated protein kinase cascade to regulate innate immunity in plants Gao M*, Liu J*, Bi D, Zhang Z, Cheng F, Chen S, Zhang Y 期刊名称 Cell Research 期卷 18:1190–1198
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