Program Official

Principal Investigator

Leo L
Cheng
Awardee Organization

Massachusetts General Hospital
United States

Fiscal Year
2023
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Novel metabolomic contrast probes for human lung cancer characterization

Novel metabolomic contrast probes for human lung cancer characterization We identified preliminary proof-of-concept metabolomic markers for human LuCa from paired tissue and blood serum samples from pre-symptomatic LuCA patients. The markers can be used as imaging probes for Luca characterization. To validate the efficacy of the markers for classifying LuCa, we propose to evaluate and enhance their capability as probes for LuCa detection and ultimately advance LuCa early-detection using serum metabolomic markers. The project’s goal will be achieved through tasks in the following three specific aims: 1) To evaluate the efficacy of tissue-serum LuCa MRS metabolomic probes identified in a successful preliminary project, by comparison with an additional 200 pairs of tissue and serum specimens and 200 serum samples from matched healthy controls, 2) To measure tissue-serum LuCa MRS metabolomic probes with mass spectrometry (MS) and MS imaging (MSI) to associate the probes with LuCa pathologies and identify serum MS LuCa probes, and 3) To test LuCa metabolomics probes using 200 serum samples collected before LuCa detection and evaluate LuCa metabolomic probe health- and cost-effectiveness as compared to existing advanced tests. The project’s goal is to identify a novel serum contrast probe able to contribute to LuCa early disease detection at asymptomatic stages to overcome persistent challenges currently faced in the LuCa clinic.

Publications

  • Muti IH, Gonzalez Sanchez-Dahl M, Zhong AB, Weng J, Füzesi MV, Kivisäkk P, Hyman BT, Arnold SE, Feldman AS, Mercaldo ND, Cheng LL. Designing a quality assurance process for quality control of nuclear magnetic resonance metabolomics studies of human blood. NMR in biomedicine. 2023 Apr;36(4):e4868. Epub 2022 Dec 12. PMID: 36330660
  • Hasubek AL, Wang X, Zhang E, Kobus M, Chen J, Vandergrift LA, Kurreck A, Ehret F, Dinges S, Hohm A, Tilgner M, Buko A, Habbel P, Nowak J, Mercaldo ND, Gusev A, Feldman AS, Cheng LL. Differentiation of patients with and without prostate cancer using urine 1 H NMR metabolomics. Magnetic resonance in chemistry : MRC. 2023 Dec;61(12):740-747. Epub 2023 Sep 1. PMID: 37654196
  • Vandergrift LA, Wang N, Zhu M, Li B, Chen S, Habbel P, Nowak J, Mason RP, Grant A, Wang Y, Malloy C, Cheng LL. 13 C NMR quantification of polyamine syntheses in rat prostate. NMR in biomedicine. 2023 Aug;36(8):e4931. Epub 2023 Apr 23. PMID: 36939957
  • Broeckling CD, Beger RD, Cheng LL, Cumeras R, Cuthbertson DJ, Dasari S, Davis WC, Dunn WB, Evans AM, Fernández-Ochoa A, Gika H, Goodacre R, Goodman KD, Gouveia GJ, Hsu PC, Kirwan JA, Kodra D, Kuligowski J, Lan RS, Monge ME, Moussa LW, Nair SG, Reisdorph N, Sherrod SD, Ulmer Holland C, Vuckovic D, Yu LR, Zhang B, Theodoridis G, Mosley JD. Current Practices in LC-MS Untargeted Metabolomics: A Scoping Review on the Use of Pooled Quality Control Samples. Analytical chemistry. 2023 Dec 26;95(51):18645-18654. Epub 2023 Dec 6. PMID: 38055671
  • Pavao A, Zhang E, Monestier A, Peltier J, Dupuy B, Cheng L, Bry L. HRMAS 13C NMR and genome-scale metabolic modeling identify threonine as a preferred dual redox substrate for Clostridioides difficile. bioRxiv : the preprint server for biology. 2023 Sep 18. PMID: 37786668