Developing Powerful MS Assays in Metabolomics
Mass spectrometry-based methods play an important role in metabolomics for detecting and quantifying metabolites and metabolic flux. The Gu Lab’s previous research lie predominantly in the following areas: 1) expanding the detectable metabolite coverage, 2) improving metabolite quantitation combining both NMR and MS, and 3) developing novel metabolic flux analysis approaches. Currently, the lab performs metabolic measurement of more than 2,500 small molecules (MW<2,000 Da) on a routine basis. Gu and his team have developed advanced targeted and untargeted metabolite profiling methods, for both metabolite level measurements and metabolic flux analysis.
- H. Gu, H. Chen, Z. Pan, A. U. Jackson, N. Talaty, B. Xi, C. Kissinger, C. Duda, D. Mann, D. Raftery, R. G. Cooks, “Monitoring Diet Effects from Biofluids and Their Implications for Metabolomics Studies”, Anal. Chem., 79, 89-97, 2007. PMID: 17194125
- H. Gu, P. Zhang, J. Zhang, D. Raftery, “Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage”, Anal. Chem., 87, 12355-12362, 2015. PMID: 26579731
- H. Gu, P. Carroll, J. Du, J. Zhu, F. Carnevale Neto, R. Eisenman, and D. Raftery, “Quantitative Method to Investigate the Balance between Metabolism and Proteome Biomass: Starting from Glycine”, Angew. Chem. Int. Ed., 55, 15646-15650, 2016. PMID: 27860107
- X. Shi, S. Wang, P. Jasbi, C. Turner, J. Hrovat, Y. Wei, J. Liu, and H. Gu, "Database Assisted Globally Optimized Targeted Mass Spectrometry (dGOT-MS): Broad and Reliable Metabolomics Analysis with Enhanced Identification", Anal. Chem., 21, 13737-13745, 2019, PMID: 31556994
Environmental contaminants, gut microbiome, and health
The Gu Lab uses multiple biological approaches to investigate to what extent environmental contaminants modulate gut microbiome, metabolism homeostasis, and eventually human health. The lab has shown that 1) there is a novel interaction between PBDEs and the endogenous BA-signaling through modification of the “gut-liver axis,” 2) PBDEs impact intermediary metabolism, including SCFAs, in an intestinal microbiome–dependent manner, suggesting that microbiome dysbiosis may contribute to PBDE-mediated toxicities that include metabolic syndromes, and 3) PXR and CAR activation downregulates BA-metabolizing bacteria in the intestine and modulates BA homeostasis in a gut microbiota-dependent manner.
- D. Scoville, C. Y. Li, D. Wang, J. L. Dempsey, D. Raftery, S. Mani, H. Gu, J. Y. Cui, “Polybrominated Diphenyl Ethers and Gut Microbiome Modulate Metabolic Syndrome-Related Aqueous Metabolites in Mice”, Drug Metab Dispos, 47, 928-940, 2019. PMID: 31123037
- J. Dempsey, D. Wang, G. Siginir, Q. Fei, D. Raftery, H. Gu, J. Y. Cui, “Pharmacological Activation of PXR and CAR Downregulates Distinct Bile Acid-Metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis”, Toxicol Sci., 168, 40-60, 2019. PMID: 30407581
- B. Zhu, H. Cao, G. Li, W. Du, G. Xu, J. Santo Domingo, H. Gu, N. Xu, S. Duan, J. Lu, "Biodiversity and dynamics of cyanobacterial communities during blooms in temperate lake (Harsha Lake, Ohio, USA)", J. Harmful Algae, 82, 9-18, 2019. PMID 30928013
- C. Li, J. L. Dempsey, D. Wang, S. Lee, K. M. Weigel, Q. Fei, D. K. Bhatt, B. Prasad, D. Raftery, H. Gu, J. Y. Cui, “PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice”, Drug Metab. Dispos., 46, 1226-1240, 2018. PMCID: PMC6053593
Metabolomics Applications in Biomarker Discovery and Systems Biology
The lab has spent intensive efforts applying metabolomics in biomarker discovery and systems biology research. Gu has found significant metabolite signatures associated with obesity among Mexican Americans, which can eventually reduce health disparities. Researchers have identified promising metabolite biomarker candidates in kidney, liver, colon, esophageal, ovarian, and breast cancers. The lab is currently validating these metabolites and models using additional samples obtained from other collection sites. In addition, the metabolomics approaches have been successfully used in a growing number of studies, including metabolic reprogramming during Myc-regulated tumorigenesis, cardiac metabolic shifts induced by rapamycin, metabolic characterization of mammalian skeletal muscles, metabolome regulation during naive-to-primed human embryonic stem cell transition, epigenetic-induced metabolic changes that can be targeted for novel therapeutic approaches.
- H. Sperber, J. Mathieu, Y. Wang, A. Ferreccio, J. Hesson, Z. Xu, K. A. Fischer, A. Devi, D. Detraux, H. Gu, S. L. Battle, M. Showalter, C. Valensisi, J. H. Bielas, N. G. Ericson, L. Margaretha, A. M. Robitaille, D. Margineantu, O. Fiehn, D. Hockenbery, C. A. Blau, D. Raftery, A. A. Margolin, R. D. Hawkins, R. T. Moon, C. B. Ware, H. Ruohola-Baker, “The Metabolome Regulates the Epigenetic Landscape During Naive-to-Primed Human Embryonic Stem Cell Transition”, Nat. Cell Bio., 17, 1523-1535, 2015. PMCID: PMC4662931
- P. Carroll, D. Diolaiti, L. McFerrin, H. Gu, D. Djukovic, J. Du, P. Cheng, S. Anderson, M. Ulrich, J. Hurley, D. Raftery, D. Ayer, R. Eisenman, “Deregulated Myc Requires MondoA/Mlx for Metabolic Reprogramming and Tumorigenesis”, Cancer Cell, 27, 271-285, 2015. PMCID: PMC4326605
- M. Buas, H. Gu, D. Djukovic, J. Zhu, L. Onstad, B. Reid, D. Raftery, T. Vaughan, “Candidate serum metabolite biomarkers for differentiating gastroesophageal reflux disease, Barrett's esophagus, and high-grade dysplasia/esophageal adenocarcinoma”, Metabolomics, 13, 23, 2017. PMCID: PMC5295138
- P. Jasbi, D. Wang, L. Cheng, Q. Fei, Y. Cui, L. Liu, Y. Wei, D. Raftery, H. Gu, “Breast cancer detection using targeted plasma metabolomics”, J. Chromatogr. B, 1105, 26-37, 2019. PMID: 30562627