The proposed work focuses on the development of advanced methods in nuclear magnetic resonance (NMR) spectroscopy for metabolomics-based studies. The rapidly expanding field of metabolomics provides new information on biological perturbations based on multiple changes in small molecule metabolite signals. New advances in NMR spectroscopy and their combination with mass spectrometry (MS) and multivariate statistical methods provide a promising approach for a number of biological applications including early disease diagnosis, treatment monitoring, drug development and basic investigations in systems biology. While the metabolome is known to provide an instantaneous snap-shot of health status, the identification and validation of potential biomarkers of health and disease is challenging due to the complexity of their overlapping signals in biological samples. Over the past several years, we have developed a new set of advanced NMR tools that can be brought to bear on this problem, with the promise that we can significantly increase the ability of NMR to dissect the complex samples and identify sensitive and specific metabolite biomarker candidates. In particular we propose three advanced NMR methods that are expected to improve the limit of detection of metabolites in biofluids by 10-fold and increase the number of NMR-detectible metabolites by a similar factor. This development would change the current paradigm in NMR-based metabolomics and provide an even stronger complement to current MS-based methods. Validation of these methods on a set of commercial serum samples and a comparison of these new approaches to current methods are also discussed. If this work is successful, we will have laid the foundation for much improved metabolomics studies for applications ranging from early disease detection and therapy monitoring to basic studies of systems biology.

Public Health Relevance

This project seeks to develop new and advanced methods for identifying biomarkers of disease in serum and urine samples. When fully developed these approaches could be used to detect small molecules in the blood or urine that indicate the onset of various diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Wehrle, Janna P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Purdue University
Schools of Arts and Sciences
West Lafayette
United States
Zip Code
Nagana Gowda, G A; Djukovic, Danijel; Bettcher, Lisa Fan et al. (2018) NMR-Guided Mass Spectrometry for Absolute Quantitation of Human Blood Metabolites. Anal Chem 90:2001-2009
Markley, John L; Br├╝schweiler, Rafael; Edison, Arthur S et al. (2017) The future of NMR-based metabolomics. Curr Opin Biotechnol 43:34-40
Nagana Gowda, G A; Raftery, Daniel (2017) Recent Advances in NMR-Based Metabolomics. Anal Chem 89:490-510
Parent, Brodie A; Seaton, Max; Djukovic, Danijel et al. (2017) Parenteral and enteral nutrition in surgical critical care: Plasma metabolomics demonstrates divergent effects on nitrogen, fatty-acid, ribonucleotide, and oxidative metabolism. J Trauma Acute Care Surg 82:704-713
Nagana Gowda, G A; Raftery, Daniel (2017) Whole Blood Metabolomics by 1H NMR Spectroscopy Provides a New Opportunity To Evaluate Coenzymes and Antioxidants. Anal Chem 89:4620-4627
Gu, Haiwei; Carroll, Patrick A; Du, Jianhai et al. (2016) Quantitative Method to Investigate the Balance between Metabolism and Proteome Biomass: Starting from Glycine. Angew Chem Int Ed Engl 55:15646-15650
Carnevale Neto, Fausto; Pilon, Alan C; Selegato, Denise M et al. (2016) Dereplication of Natural Products Using GC-TOF Mass Spectrometry: Improved Metabolite Identification by Spectral Deconvolution Ratio Analysis. Front Mol Biosci 3:59
Zhou, Xuanzhu; Zheng, Wei; Nagana Gowda, G A et al. (2016) 1,25-Dihydroxyvitamin D inhibits glutamine metabolism in Harvey-ras transformed MCF10A human breast epithelial cell. J Steroid Biochem Mol Biol 163:147-56
Parent, Brodie A; Seaton, Max; Sood, Ravi F et al. (2016) Use of Metabolomics to Trend Recovery and Therapy After Injury in Critically Ill Trauma Patients. JAMA Surg 151:e160853
Deng, Lingli; Gu, Haiwei; Zhu, Jiangjiang et al. (2016) Combining NMR and LC/MS Using Backward Variable Elimination: Metabolomics Analysis of Colorectal Cancer, Polyps, and Healthy Controls. Anal Chem 88:7975-83

Showing the most recent 10 out of 50 publications