Center PI

Zeping Hu

Emailzeping_hu@.tsinghua.edu.cn

TEL:+86-10-62799839Lab

Webpage: https://www.sps.tsinghua.edu.cn/info/1011/1427.htm

Research Area

Our lab has long been dedicated to studying metabolic reprogramming and translational medicine in major diseases such as cancer, as well as developing innovative metabolomics and multi-omics technologies.

Many major diseases—including cancer and cardiovascular disorders—are closely linked to metabolic abnormalities. Therefore, elucidating the functional roles and regulatory mechanisms underlying these metabolic changes not only advances our understanding of fundamental metabolic biology but also helps identify key pathways or nodes that could serve as potential drug targets.

In recent years, our research has increasingly focused on the emerging field of cancer neuroscience, exploring metabolic interactions among various cell types (including tumor, neuronal, immune, and fibroblast cells) within cells and the tissue microenvironment. We study single-cell metabolic heterogeneity and how these processes influence tumor progression and drug resistance. In particular, we are interested in the roles and regulatory mechanisms of neurotransmitters and neuropeptides in mediating metabolic interactions and heterogeneity among tumor, neural, and immune cells in the tumor microenvironment.

At the same time, our lab actively develops novel technologies to meet the technical demands of disease metabolism research. These include ultrasensitive micro-metabolomics, single-cell metabolomics, and AI-assisted multi-omics integration technologies. Through these efforts, we aim to identify potential drug targets and biomarkers, providing scientific foundations for new drug discovery and precision medicine.

Selected Publications

Research Articles

1.Chen Y#, Wang B#, Zhao Y#, Shao X#, Wang M#, Ma F#, Yang L, Nie M, Jing P, Yao K, Song H, Lou S, Wang H, Yang T, Tian Y*, Han P*, Hu ZP*. Metabolomic 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.  

3.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

4.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.  

5.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

6.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.

7.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.

8.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.

9.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.

10.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.

11.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.

12.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.

13.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.

Invited Opinions/Reviews/Viewpoints

14.Xu Y, Jiang X, Hu ZP*. Synergizing metabolomics and artificial intelligence for advancing precision oncology. Trends in Molecular Medicine. 2025:S1471-4914(25)00016-4.

15.Nie M, Hu ZP. Metabolic orchestration of drug-tolerant persister cells in cancer. Life Medicine. 2024;3(6):lnae040.

16.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.

17.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.

18.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.

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

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

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

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