药物新靶点的发现与确证是原创药物研发的关键。近年的研究表明，癌症、心力衰竭、免疫性疾病等重大疾病均与代谢异常密切相关。此外，肿瘤微环境（TME）中不同细胞（包括癌细胞、免疫细胞、神经元、成纤维细胞、内皮细胞等）之间存在复杂的相互调控关系，包括代谢相互作用。特别是越来越多的证据提示，神经系统是显著调节癌症发生发展、转移和耐药的关键调节者；而反过来，癌症也会重塑和劫持神经系统的结构和功能因此，深入探究TME中代谢重塑的功能与调控机制，特别是神经系统与癌细胞、免疫细胞等之间的代谢互作，有望精准、高效地发现具有治疗潜力的关键通路或分子，从而为转化医学和药物研发提供潜在新药靶点。

胡泽平实验室通过开发新型代谢组学和多组学整合技术，结合生物信息和AI技术，利用细胞、分子和代谢生物学等方法，深入探究肿瘤和心血管疾病的微环境代谢互作与调控机制，为其治疗提供新思路和潜在新药靶点。主要研究方向包括：

·TME中不同细胞间的代谢互作与单细胞代谢异质性：利用前沿微量代谢组学和单细胞多组学技术，系统解析TME中不同类型细胞的代谢重塑、功能及其相互作用机制，并揭示代谢异质性及其生物学功能与调控机制。

·TME中神经元与癌细胞或免疫细胞间的代谢互作：系统探究肺癌和胰腺癌TME中，神经元与癌细胞、免疫细胞之间的相互作用机制及关键调控分子，特别是神经递质/神经肽对TME不同细胞的作用，鉴定可作为潜在治疗靶点的代谢互作机制。

·抗癌治疗耐受性（drug tolerant persister, DTP）的代谢调控：从时空尺度探究抗癌治疗响应期、药物耐受状态（DTP）及获得性耐药过程中的代谢演变和动态变化，解析DTP细胞与TME中不同类型细胞间的代谢互作与调控机制。

·心血管微环境的代谢重塑和调控机制：探索心血管疾病微环境中不同类型细胞间的代谢互作和调控，阐释其在心衰发生发展中的功能与机制。

·跨尺度代谢组学和AI辅助多组学大数据分析技术：研发基于质谱的高精准、超灵敏、单细胞跨尺度代谢组学/代谢流技术，揭示组织微环境的代谢重塑规律，并阐释其分子调控机制；开发AI辅助的多组学大数据整合分析技术，从多维度分子层面揭示代谢重塑规律与机制。

- 2017年 拜耳学者奖（Bayer Investigator Award）

- 2019年 第十四届全国医药卫生青年科技论坛二等奖

- 2019年 年度优秀委员，中国抗癌协会肿瘤代谢专委会

- 2019年 优秀教学奖，清华大学药学院

- 2020年 拜耳学者奖（Bayer Investigator Award）

- 2022年 清华大学优秀博士论文导师

- 2022年 教育部“长江学者”特聘教授

参编教材

- 《高等药物分析学》副主编，2021年，人民卫生出版社，全国高校药学类研究生规划教材

（按时间倒序，*通讯作者；#第一作者）

研究论文（通讯作者）

1. Chen Y^#, Wang B^#, Zhao Y^#, Shao X^#, Wang M^#, Ma F^#, Yang L, Nie M, Jin P, Yao K, Song H, Lou S, Wang H, Yang T, Tian Y*, Han P*, Hu ZP*. Metabolomics machine learning predictor of diagnosis and prognosis of gastric cancer. Nature Communications. 2024;15(1):1657.

2. Fan H^#, Xu Z^#, Yao K^#, Zheng B, Zhang Y, Wang X, Zhang T, Li X, Hu H, Yue B*, Hu ZP*, Zheng H*. Osteoclast cancer cell metabolic cross-talk confers PARP inhibitor resistance in bone metastatic breast cancer. Cancer Research. 2024;84(3):449-467. 被选为同期Featured Article.

3. Liu Y^#, Fan X^#, Pang H^#, Liu S^#, Wang B, Wang C, Yan Q, Song W, Hu ZP*, Liu Q*, Shi Y*. Metabolomics identifies a panel of diagnostic biomarkers for early human embryonic development arrest. Journal of Proteome Research. 2023;22(4):1280-1286.

4. Nie M^#, Chen N^#, Pang H^#, Jiang T^#, Jiang W, Tian P, Yao L, Chen Y, DeBerardinis RJ, Li W, Yu Q, Zhou C, Hu ZP*. Targeting acetylcholine signaling modulates persistent drug tolerance in EGFR-mutant lung cancer and impedes tumor relapse. Journal of Clinical Investigation. 2022;132(20):e160152.

5. Yuan M^#, Tu B^#, Li H^#, Pang H^#, Zhang N, Bai J, Shu Z, Christopher C, Huo S, Zhai J, Yao K, Wang L, Ying H, Zhu WG, Fu D, Hu ZP*, Zhao Y*. Cancer associated fibroblasts employ NUFIP1-dependent autophagy to secrete nucleosides and support pancreatic tumor growth. Nature Cancer. 2022;3(8):945-960. 被Nature Cancer 的News & Views评论 (Tumor Microenvironment: NUFIP1+ stroma keeps PDAC fed, https://www.nature.com/articles/s43018-022-00421-x)

6. Wang W^#, Wang J^#,*, Yao K^#, Wang S^#, Nie M, Xu J, Wu G, Lu M, Pei H, Luo X, Li D, Yang T, Li P, Song L*, Hu ZP*. Metabolic characterization of hypertrophic cardiomyopathy in human hearts. Nature Cardiovascular Research. 2022;1:445–461.

7. Jiang Y*^,#, Deng Y^#, Pang H^#, Ma T, Ye Q, Chen Q, Chen H, Hu ZP*, Qin CF*, Xu Z*. Treatment of SARS-CoV-2 induced pneumonia with NAD⁺ and NMN in two mouse models. Cell Discovery. 2022;8(1):38.

8. Cheng W^#, Pang H^#, Campen MJ, Zhang J, Li Y, Gao J, Ren D, Ji X, Rothman N, Lan Q, Zheng Y, Leng S*, Hu ZP*, Tang J*. Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically. Particle and Fibre Toxicology. 2022;19(1):20.

9. Nie M^#, Yao K^#, Zhu X^#, Chen N, Xiao N, Wang Y, Peng B, Yao LA, Li P, Zhang P*, Hu ZP*. Evolutionary metabolic landscape from preneoplasia to invasive lung adenocarcinoma with therapeutic implications. Nature Communications. 2021;12(1):6479. 被Nature Reviews Cancer 选为Research Highlights (Metabolic Transitions, https://www.nature.com/articles/s41568-021-00438-x)

10. Zhao J^#, Yao K^#, Yu H^#, Zhang L^#, Xu Y^#, Chen L, Sun Z, Zhu Y, Zhang C, Qian Y, Ji S, Pang H, Zhang M, Chen J, Correia C, Weiskittel T, Lin DW, Zhao Y, Chandrasekaran S, Fu X, Zhang D, Fan HY, Xie W, Li H, Hu ZP*, Zhang J*. Metabolic remodeling during early murine embryo development. Nature Metabolism. 2021;3(10):1372-1384.被选为封面文章(https://www.nature.com/natmetab/volumes/3/issues/10)；被Science选为Editor’s Pick (Translational Metabolism, https://www.science.org/doi/10.1126/science.acx9416)

11. Pang H^#, Jiang Y^#, Li J^#, Wang Y^#, Nie M^#, Xiao N, Wang S, Song Z, Ji F, Chang Y, Zheng Y, Yao K, Yao L, Li S, Song L*, Lan X*, Xu Z*, Hu ZP*. Aberrant NAD⁺ metabolism underlies ZIKA virus-induced microcephaly. Nature Metabolism. 2021;3(8):1109-1124.

12. Xiao N^#, Nie M^#, Pang H^#, Wang B^#, Hu J^#, Meng X, Li K, Ran X, Long Q, Deng H, Chen N, Li S, Tang N*, Huang A*, Hu ZP*. Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications. Nature Communications. 2021;12(1):1618.

13. Meng X^#, Pang H^#, Sun F, Jin X, Wang B, Yao K, Yao L, Wang L, Hu ZP*. Simultaneous 3-nitrophenylhydrazine derivatization strategy of carbonyl, carboxyl and phosphoryl submetabolome for LC-MS/MS-based targeted metabolomics with improved sensitivity and coverage. Analytical Chemistry. 2021;93(29):10075-10083.

14. Shi Z^#, Xu S^#, Xing S, Yao K, Zhang L, Xue L, Zhou P, Wang M, Yan G, Yang P, Liu J, Hu ZP*, Lan F*. Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes. The FASEB Journal. 2019;33(11):13040-13050.

15. Huang F, Ni M, Chalishazar MD, Huffman KE, Kim J, Cai L, Shi X, Cai F, Zacharias LG, Ireland AS, Li K, Gu W, Kaushik AK, Liu X, Gazdar AF, Oliver TG, Minna JD, Hu ZP*, DeBerardinis RJ*. Inosine monophosphate dehydrogenase dependence in a subset of small cell lung cancers. Cell Metabolism. 2018;28(3):369-382.

16. Li XK^#, Lu QB^#, Chen WW^#, Xu W^#, Liu R, Zhang SF, Du J, Li H, Yao K, Zhai D, Zhang PH, Xing B, Cui N, Yang ZD, Yuan C, Zhang XA, Xu Z, Cao WC*, Hu ZP*, Liu W*. Arginine deficiency is involved in thrombocytopenia and immunosuppression in Severe Fever with Thrombocytopenia Syndrome. Science Translational Medicine. 2018;10(459): eaat4162. 被选为封面文章(https://www.science.org/toc/stm/10/459)

综述论文（通讯作者）

17. Wang F^#, Fu K^#, Wang Y, Pan C, Wang X, Liu Z, Yang C, Zheng Y, Li X, Lu Y, To KKW, Xia C, Zhang J, Shi Z, Hu ZP*, Huang M*, Fu L*. Small-molecule agents for cancer immunotherapy. Acta Pharmaceutica Sinica B (APSB). 2024;14(3):905-952.

18. Thompson CB*, Vousden KH*, Johnson RS*, Koppenol WH*, Sies H*, Lu Z*, Finley LWS*, Frezza C*, Kim J*, Hu ZP*, Bartman CR*. A century of the Warburg effect. Nature Metabolism. 2023;5(11):1840-1843.

19. Pang H, Hu ZP*. Metabolomics in drug research and development: advances in technologies and applications. Acta Pharmaceutica Sinica B (APSB). 2023;13(8):3238-3251.

20. Wang B^#, Yao K^#, Hu ZP*. Advances in mass spectrometry-based single-cell metabolite analysis. TrAC Trends in Analytical Chemistry. 2023;163:117075.

21. Liang L, Sun F, Wang H, Hu ZP*. Metabolomics, metabolic flux analysis and cancer pharmacology. Pharmacology & Therapeutics. 2021;224:107827.

22. Pang H, Jia W*, Hu ZP*. Emerging applications of metabolomics in clinical pharmacology. Clinical Pharmacology & Therapeutics. 2019;106(3):544-556.

合作研究论文（部分）

23. Hu Y, Yang Y, Tan P, Zhang Y, Han M, Yu J, Zhang X, Jia Z, Wang D, Yao K, Pang H, Hu ZP, Li Y, Ma T, Liu K, Ding S. Induction of mouse totipotent stem cells by a defined chemical cocktail. Nature. 2023;617(7962):792-797.

24. Agathocleous M, Meacham C, Burgess RJ, Piskounova E, Bruner E, Cowin B, Crane GM, Murphy MM, Hu ZP, DeBerardinis RJ, Morrison SJ. Ascorbate regulates haematopoietic stem cell function and suppresses leukaemogenesis. Nature. 2017;549(7673):476-81.

25. Kim J, Hu ZP, Cai L, Choi E, Rodriguez-Canales J, Villalobos P, Lin YF, Ni M, Unsal-Kacmaz K, Peña CG, Castrillon DH, Chen BPC, Wistuba I, Minna JD, DeBerardinis RJ. CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. Nature. 2017;546(7656):168-72.

26. Nakada Y, Canseco DC, Thet S, Abdisalaam S, Asaithamby A, Santos CX, Shah A, Zhang H, Faber JE, Kinter MT, Szweda LI, Xing C, Hu ZP, Deberardinis RJ, Schiattarella G, Hill JA, Oz O, Lu Z, Zhang CC, Kimura W, Sadek HA. Hypoxia induces heart regeneration in adult mice. Nature. 2017;541(7636):222-7.

27. Liu X, Zhang Y, Ni M, Cao H, Signer RAJ, Li D, Li M, Gu Z, Hu ZP, Dickerson KE, Weinberg SE, Chandel NS, DeBerardinis RJ, Zhou F, Shao Z, Xu J. Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation. Nature Cell Biology. 2017;19(6):626-38.

28. Piskounova E, Agathocleous M, Murphy MM, Hu ZP, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ, Morrison SJ. Oxidative stress inhibits distant metastasis by human melanoma cells. Nature. 2015;527(7577):186-91.

29. DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu ZP, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, Wistuba II, Minna JD, DeBerardinis RJ, Cantley LC. NRF2 regul

ates serine biosynthesis in non-small cell lung cancer. Nature Genetics. 2015;47(12):1475-81.