Metabolism is the fundament of physiology, and it has become increasingly apparent that many human diseases such as cancer and diabetes involve the perturbation of metabolism. Metabolomics is a relatively new field of systems biology that detects and quantifies metabolites and analyzes the activity of metabolic pathways. It is emerging to be a powerful technology in both biomedical and pharmaceutical research.  
 
Overall, our goals are to identify the metabolic disturbances in diseases using a variety of precise metabolic analytical techniques, understand the underlying molecular mechanisms, and design optimal therapeutic strategies. To achieve these, we aims   1) to develop cutting-edge mass spectrometry-based techniques for metabolic analysis, and use these tools   2) to elucidate the metabolic mechanisms of diseases and related drug responses (efficacy and toxicity);   3) to facilitate pharmaceutical research & development, such as the identification of novel therapeutic targets, and drug metabolism & pharmacokinetics and toxicity study of new drugs;   4) to develop new diagnostic and/or prognostic methods for monitoring disease pathogenesis/progression; and   5) to stratify patients by pharmacometabolomics phenotyping for enabling precision medicine to achieve optimal drug efficacy and toxicity.

2） We have applied the developed techniques to explore the metabolic perturbation in a number of diseases/pathologies, particularly cancer. These include the identification of new metabolic mechanisms in cancer cells, and the role of metabolism in the pathogenesis or metastasis of lung cancer and melanoma.  
3） We have investigated the effects and underlying mechanisms of coadministered St. John's wort or thalidomide (thalidomide) on the pharmacokinetics, drug metabolism, transport, and toxicity of CPT-11 (irinotecan). Meanwhile, we have completed the first preclinical pharmacokinetics study of recombinant human parathyroid hormone 1-34 in animals.

Steering Committee Member, AAPS Systems Pharmacology Focus Group, 2013 – present  
Postgraduate Fellowship, National University of Singapore, 2003-2008  
United Laboratories Medical Fellowship (Gold Prize), Shandong University, 1998

1.     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.  
2.     Zhang Y, Udayakumar D, Cai L,   Hu ZP, Kapur P, Kho EY, Pavía-Jiménez A, Fulkerson M, de Leon AD, Yuan Q, Dimitrov IE, Yokoo T, Ye J, Mitsche MA, Kim H, McDonald JG, Xi Y, Madhuranthakam AJ, Dwivedi DK, Lenkinski RE, Cadeddu JA, Margulis V, Brugarolas J, DeBerardinis RJ, Pedrosa I. Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI.   JCI Insight. 2017;2(15). pii: 94278.  
3.     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; 546:168-172  
4.     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. Under review   Nature Cell Biology. 2017;19:626–638  
5.     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, Hesham A. Sadek HA. Hypoxia induces heart regeneration in adult mice.   Nature. 2017; 541(7636):222-7.  
6.     Zeng M,    Hu ZP, Shi X, Li X, Zhan X, Li XD, Wang J, Choi JH, Wang KW, Purrington T, Tang M, Fina M, DeBerardinis RJ, Moresco EM, Pedersen G, McInerney GM, Karlsson Hedestam GB, Chen ZJ, Beutler B. MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses.    Science. 2014; 346(6216):1486-92.  
7.     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.  
8.     Curtis MM,    Hu ZP, Klimko C, Narayanan S, Deberardinis R, Sperandio V. The gut commensal    Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape.    Cell Host & Microbe. 2014; 16(6):759-69.  
9.     Mullen AR,    Hu ZP, Shi X, Jiang L, Boroughs LK, Kovacs Z, Boriack R, Rakheja D, Sullivan LB, Linehan WM, Chandel NS, DeBerardinis RJ. Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects.    Cell Reports. 2014; 7(5):1679-90.  
10.  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 regulates serine biosynthesis in non-small cell lung cancer.    Nature Genetics. 2015; 47(12):1475-81.  
11.  Srivastava N, Kollipara RK, Singh DK, Sudderth J,    Hu ZP, Nguyen H, Wang S, Humphries CG, Carstens R, Huffman KE, DeBerardinis RJ, Kittler R. Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.    Cell Metabolism. 2014; 20(4):650-61.  
12.    Hu ZP, Browne ER, Liu T, Angel TE, Ho PC, Chan EC. Metabonomic profiling of TASTPM transgenic Alzheimer's disease mouse model.    Journal of Proteome Research. 2012; 11(12):5903-13.  
13.    Hu ZP, Kim YM, Sowa MB, Robinson RJ, Gao X, Metz TO, Morgan WF, Zhang Q. Metabolomic response of human skin tissue to low dose ionizing radiation.    Molecular BioSystems. 2012; 8(7):1979-86.  
14.    Hu ZP   ^§, Yang XX   ^§, Chen X, Cao J, Chan E, Duan W, Huang M, Yu XQ, Wen JY, Zhou SF. A mechanistic study on altered pharmacokinetics of irinotecan by St. John's wort.    Current Drug Metabolism. 2007; 8(2):157-71. (   §, co-first author)  
15.    Hu ZP   ^§, Yang XX   ^§, Chan SY, Xu AL, Duan W, Zhu YZ, Sheu FS, Boelsterli UA, Chan E, Zhang Q, Wang JC, Ee PL, Koh HL, Huang M, Zhou SF. St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis.    Toxicology and Applied Pharmacology. 2006; 216(2):225-37. (   §, co-first author)  
16.  Yang XX   ^§,    Hu ZP   ^§, Xu AL, Duan W, Zhu YZ, Huang M, Sheu FS, Zhang Q, Bian JS, Chan E, Li X, Wang JC, Zhou SF. A mechanistic study on reduced toxicity of irinotecan by coadministered thalidomide, a tumor necrosis factor-alpha inhibitor.    Journal of Pharmacology and Experimental Therapeutics. 2006; 319(1):82-104. (   §, co-first author)  
17.    Hu ZP*, Niu H, Yang X, Li H, Sang G, Li B. Recombinant human parathyroid hormone 1-34: pharmacokinetics, tissue distribution and excretion in rats.    International Journal of Pharmaceutics. 2006; 317(2):144-54. (   *,    corresponding author)  
18.    Hu ZP, Yang X, Ho PC, Chan E, Chan SY, Xu C, Li X, Zhu YZ, Duan W, Chen X, Huang M, Yang H, Zhou S. St. John's Wort modulates the toxicities and pharmacokinetics of CPT-11 (irinotecan) in rats.    Pharmaceutical Research. 2005; 22(6):902-14.