郵箱: mlu@sinh.ac.cn
電話: +86-21-54923270
所屬部門: 腫瘤與微環(huán)境重點(diǎn)實(shí)驗(yàn)室
2021-至 今：中國(guó)科學(xué)院上海營(yíng)養(yǎng)與健康研究所 研究員
2018-2020年：美國(guó)杰克遜實(shí)驗(yàn)室 訪問學(xué)者
2014-2021年：復(fù)旦大學(xué)附屬華山醫(yī)院普外科/復(fù)旦大學(xué)腫瘤轉(zhuǎn)移研究所 助理/副研究員
2011-2014年：中國(guó)科學(xué)院上海生命科學(xué)研究院生化與細(xì)胞所 博士后
2004-2010年：中國(guó)科學(xué)院上海生命科學(xué)研究院生化與細(xì)胞所 博士
2000-2004年：四川大學(xué)，生命科學(xué)學(xué)院 學(xué)士
脂質(zhì)代謝物感知與腫瘤轉(zhuǎn)移
代謝是生命的基本特征之一。脂質(zhì)是一類復(fù)雜多樣的重要代謝物。它們不僅是細(xì)胞能量和物質(zhì)合成的重要來源，特定脂質(zhì)代謝物還可作為細(xì)胞膜的關(guān)鍵組分和代謝物信號(hào)發(fā)揮關(guān)鍵的調(diào)控作用。我們關(guān)注脂質(zhì)代謝物的變化是如何被細(xì)胞感知及其異常相關(guān)疾病的調(diào)控機(jī)理，主要開展兩方面的研究：
1. 脂質(zhì)代謝異常調(diào)控腫瘤轉(zhuǎn)移機(jī)理及干預(yù)。轉(zhuǎn)移是惡性腫瘤致死的最主要原因。腫瘤轉(zhuǎn)移是一個(gè)復(fù)雜多步驟的過程， 至少包括高侵襲性腫瘤細(xì)胞脫離原發(fā)灶、通過免疫逃逸沿血管或淋巴轉(zhuǎn)移形成循環(huán)腫瘤細(xì)胞和在轉(zhuǎn)移靶器官定植生長(zhǎng)形成遠(yuǎn)端轉(zhuǎn)移灶三個(gè)步驟。其中遠(yuǎn)端轉(zhuǎn)移靶器官的定植生長(zhǎng)是腫瘤轉(zhuǎn)移的關(guān)鍵限速步驟。腫瘤細(xì)胞在轉(zhuǎn)移靶器官的微環(huán)境中面臨營(yíng)養(yǎng)物質(zhì)匱乏的嚴(yán)苛條件，轉(zhuǎn)移微環(huán)境中的特定代謝物特別是脂質(zhì)代謝物是腫瘤細(xì)胞存活和定植生長(zhǎng)的關(guān)鍵因素。我們通過代謝質(zhì)譜成像、空間轉(zhuǎn)錄組學(xué)等技術(shù)研究腫瘤細(xì)胞與轉(zhuǎn)移微環(huán)境中的間質(zhì)細(xì)胞（包括炎癥免疫細(xì)胞和基質(zhì)細(xì)胞等）在脂質(zhì)代謝水平的相互作用，揭示代謝微環(huán)境在腫瘤定植生長(zhǎng)中的功能及作用機(jī)制，探索靶向代謝微環(huán)境的腫瘤轉(zhuǎn)移干預(yù)新策略。
2. 脂質(zhì)代謝物的細(xì)胞感知機(jī)制及其異常相關(guān)疾病。近年來的前沿性進(jìn)展表明，脂質(zhì)代謝物不僅可為細(xì)胞提供能量物質(zhì)，特定脂質(zhì)代謝物的變化還可以引起細(xì)胞表型（增殖、遷移和干性等）的改變，然而具體機(jī)制還亟待深入研究。我們主要研究脂質(zhì)代謝物（重點(diǎn)關(guān)注固醇和脂肪酸）的變化是如何被細(xì)胞感知并轉(zhuǎn)化為細(xì)胞表型改變的分子機(jī)制，進(jìn)一步揭示這些感知機(jī)制在癌轉(zhuǎn)移、細(xì)胞氧化還原狀態(tài)和組織器官穩(wěn)態(tài)維持中的功能作用。
1. Shen L#, Wang SH#, Gao C#, Li Q, Feng SY, Sun WY, Liu X, Ba YY, Chu YH, Zhou Y, Pan JJ, Xu H, Zhang X, Zhu WW*, Qin LX*, Lu M*. Tumour-associated macrophages serve as an acetate reservoir to drive hepatocellular carcinoma metastasis. Nat Metab 2025;7(11):2268-2283.
2. Pan JJ#, Xie SZ#, Zheng X, Xu JF, Xu H, Yin RQ, Luo YL, Shen L, Chen ZR, Chen YR, Yu SZ, Lu L, Zhu WW*, Lu M*, Qin LX*. Acetyl-CoA metabolic accumulation promotes hepatocellular carcinoma metastasis via enhancing CXCL1-dependent infiltration of tumor-associated neutrophils. Cancer Letters 2024;592:216903.
3. Shao WQ#, Zhu WW#, Luo MJ, Fan MH, Li Q, Wang SH, Lin ZF, Zhao Jing, Zheng Yan, Dong QZ, Lu L, Jia HL, Zhang JB, Lu M*, Chen JH*, Qin LX*. Cholesterol suppresses GOLM1-dependent selective autophagy of RTKs in hepatocellular carcinoma. Cell Rep 2022;39(3):110712.
4. Zhang KL#, Zhu WW#, Wang SH#, Gao C, Pan JJ, Du ZG, Lu L, Jia HL, Dong QZ, Chen JH*, Lu M*, Qin LX*. Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer. Theranostics 2021;11(13):6560-6572.
5. Wei R#, Zhu WW#, Yu GY#, Wang X, Gao C, Zhou X, Lin ZF, Shao WQ, Wang SH, Lu M*, Qin LX*. S100A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma. Int J Cancer 2021;148(5):1233-1244.
6. Li PS#, Lu M#, Shi JY, Gong Z, Hua L, Li Q, Leonard S, Ren GW*. Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis. Nat Immunol 2020;21(11):1444-1455.
7. Li PS#, Lu M#, Shi JY, Hua L, Gong Z, Li Q, Leonard S, Ren GW*. Dual roles of neutrophils in metastatic colonization are governed by the host NK cell status. Nat Commun 2020;11(1):4387.
8. Zhu WW#, Lu M#, Wang XY#, Zhou X, Gao C, Qin LX*. The fuel and engine: the roles of reprogrammed metabolism in metastasis of primary liver cancer. Genes Dis 2020;7(3):299-307.
9. Shao WQ#, Zhu WW#, Lin J#, Luo M, Lin ZF, Lu L, Jia HL, Qin LX*, Lu M*, Chen JH*. Liver X Receptor Agonism Sensitizes a Subset of Hepatocellular Carcinoma to Sorafenib by Dual-Inhibiting MET and EGFR. Neoplasia 2020;22(1):1-9.
10. Lu M#*, Zhu WW#, Wang X, Tang JJ, Zhang KL, Yu GY, Shao WQ, Lin ZF, Wang SH, Lu L, Zhou J, Wang LX, Jia HL, Dong QZ, Chen JH, Lu JQ, Qin LX*. ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition. Cell Metab 2019;29(4):886-900.
11. Lu M#, Lu L#, Dong QZ, Yu GY, Chen JH, Qin LX, Wang LX*, Zhu WW*, Jia HL*. Elevated G6PD expression contributes to migration and invasion of hepatocellular carcinoma cells by inducing epithelial-mesenchymal transition. Acta Biochim Biophys Sin (Shanghai) 2018;50(4):370–380.
12. Wang YJ, Bian Y, Luo J, Lu M, Xiong Y, Guo SY, Yin HY, Lin X, Li Q, Chang CCY, Chang TY, Li BL*, Song BL*. Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation. Nat Cell Biol 2017;19(7):808-819.
13. Ye QH#, Zhu WW#, Zhang JB#, Qin Y#, Lu M#, Lin GL, Guo L, Zhang B, Lin ZH, Roessler S, Forgues M, Jia HL, Lu L, Zhang XF, Lian BF, Xie L, Dong QZ, Tang ZY, Wang XW*, Qin LX*. GOLM1 Modulates EGFR/RTK Cell-Surface Recycling to Drive Hepatocellular Carcinoma Metastasis. Cancer cell 2016;30(3):444-458.
14. Lu M#, Hu XH#, Li Q, Xiong Y, Hu GJ, Xu JJ, Zhao XN, Wei XX, Chang CC, Liu YK, Nan FJ, Li J, Chang TY, Song BL*, Li BL*. A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth. J Mol Cell Biol 2013;5(6):404-415.
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