Zeping Hu
Email：zeping_hu@.tsinghua.edu.cn
TEL：＋86-10-62799839（Lab）
Webpage: https://www.sps.tsinghua.edu.cn/info/1011/1427.htm
Research Area
Our laboratory is dedicated to exploring the patterns, functions, and regulatory mechanisms of metabolic reprogramming in diseases especially cancer and cardiovascular diseases, discovering new drug targets, and developing new metabolomics/multi-omics technologies. The identification of new drug targets is a critical bottleneck severely restricting current drug development efforts. Many major diseases, including cancer, cardiovascular diseases, and diabetes, are closely related to metabolic abnormalities. Therefore, in-depth research into the functional and regulatory mechanisms of disease-related metabolic abnormalities can not only answer fundamental questions in basic metabolic biology but also holds the promise of identifying key pathways or nodes as potential new drug targets.
Our lab focuses on exploring the metabolic interactions among different types of cells (including tumor, neuronal, immune, fibroblast, etc.) within the cells and the tissue microenvironment, as well as the heterogeneity of single-cell metabolism, and their roles in the development and drug resistance of tumors and cardiovascular diseases. Through these studies, we aim to uncover potential therapeutic targets and biomarkers, providing a scientific foundation and basis for the development of new precision diagnosis and treatment strategies. We pay special attention to the role and regulatory mechanisms of neurotransmitters/neuropeptides in promoting metabolic interactions and single-cell metabolic heterogeneity among tumor, neuronal, and immune cells within the tumor microenvironment. Meanwhile, our laboratory also focuses on the technical needs for disease metabolic reprogramming, developing state-of-the-art ultra-sensitive micro metabolomics, single-cell metabolomics technologies, and artificial intelligence (AI)-facilitated integration of multi-omics technologies.
Selected Publications
Research articles
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.
Selected as Featured Article.
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.
Highlighted in Nature Cancer as News & Views (Tumor Microenvironment: NUFIP1+ stroma keeps PDAC fed, https://www.nature.com/articles/s43018-022-00421-x)
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(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.
Highlighted in Nature Reviews Cancer as Research Highlights (Metabolic Transitions, https://www.nature.com/articles/s41568-021-00438-x)
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. Nature Metabolism. 2021;3(10):1372-1384.
Featured as the cover story (https://www.nature.com/natmetab/volumes/3/issues/10)；Highlighted in Science as Editor’s Pick (Translational Metabolism, https://www.science.org/doi/10.1126/science.acx9416)
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.e5.
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.
Featured as the cover story (https://www.science.org/toc/stm/10/459)
Reviews and Viewpoints
14. 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. (Invited Review)
15. 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.
16. 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. (Invited Review)
17. Wang B#, Yao K#, Hu ZP*. Advances in mass spectrometry-based single-cell metabolite analysis. TrAC Trends in Analytical Chemistry. 2023;163:117075. (Invited Review)
18. Liang L, Sun F, Wang H, Hu ZP*. Metabolomics, metabolic flux analysis and cancer pharmacology. Pharmacology & Therapeutics. 2021;224:107827. (Invited Review)
19. Pang H, Jia W*, Hu ZP*. Emerging applications of metabolomics in clinical pharmacology. Clinical Pharmacology & Therapeutics. 2019;106(3):544-556. (Invited Review)