Summary of project PR000052
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000052. The data can be accessed directly via it's Project DOI: 10.21228/M8H01X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR000052 |
| Project DOI: | doi: 10.21228/M8H01X |
| Project Title: | Metabonomic profiling of kinase inhibitor response in leukemia |
| Project Type: | Effects of kinase inhibitors in acute myeloid leukemia to understand biohemical mechanisms of disease progression and drug resistance |
| Project Summary: | The goal of this pilot project is to develop the metabonomic parameters necessary to comprehensively profile and analyze large numbers of metabolites and their drug-induced responses in cell and animal models of leukemia. Our long-term objective of these studies is to investigate the effects of select kinase inhibitors in acute myeloid leukemia (AML) in an effort to better understand biochemical mechanisms of disease progression and drug resistance. Our focus will be on FLT3-ITD kinase positive models because this is one of the most aggressive and drug-resistant types of AML. Additionally, because of the central role of the MEK/Erk kinase pathway in regulating cell proliferation and survival in these cells, inhibitors of MEK and other kinases will be tested for their effects on human and mouse metabolic profiles. We have developed a unique model of drug-resistant AML and the metabolic response of these cells to kinase inhibitors will also be evaluated. Cells will be treated with kinase inhibitors for varied times, the cells isolated and the cellular metabolites identified and quantified by mass spectrometry and NMR-based analytical methods. Bioinformatics and statistics will be performed and a comprehensive metabonomic analysis of metabolite profiles will be accomplished. Metabonomic responses will be related to specific changes in cell signaling networks. A second major objective will be to perform metabonomic analyses in response to targeted kinase inhibitors in a mouse model of FLT3-ITD AML. We will measure metabonomic profiles in mouse biofluids before and after exposure to MEK inhibitors. The specific effects of MEK or other kinase inhibitors on individual metabolites will be quantified and analyzed by bioinformatics. We anticipate that these studies will lead to the identification of unique sites of intersection between cell signaling and cell metabolism and provide the foundation for future NIH-funded research projects. |
| Institute: | University of North Carolina at Chapel Hill |
| Department: | Department of Pharmacology |
| Laboratory: | Graves Laboratory |
| Last Name: | Graves |
| First Name: | Lee |
| Address: | Pharmacology, CB7365, 411 GMB Mason Farm Road, Chapel Hill, NC 27599 |
| Email: | LMG@med.unc.edu |
| Phone: | 919-966-0915 |
Summary of all studies in project PR000052
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST000055 | Effect of kinase inhibitors on FLT3-ITD AML cell metabolomes | Mus musculus | University of North Carolina | MS | 2015-06-01 | 1 | 24 | Uploaded data (1.2G)* |
