Summary of project PR000684
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 PR000684. The data can be accessed directly via it's Project DOI: 10.21228/M8868G This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR000684 |
| Project DOI: | doi: 10.21228/M8868G |
| Project Title: | Mayo Pilot and Feasibility: H3K27M cells and glutamine metabolomics quatitation studies |
| Project Summary: | In children, tumors affecting the brain and nervous system result in more cancer-related deaths than any other type of tumor. It is thus critical to identify new approaches for therapy. Among pediatric patients, one of the most devastating brain tumor types is Diffuse Intrinsic Pontine Gliomas (DIPG). Our understanding of this deadly disease has recently been advanced by important discoveries, including the discovery that the majority of DIPG tumors harbor the histone H3K27M mutation. This mutation results in global hypomethylation of H3K27 residues and is the pathological hallmark for this disease. Glutamine (Gln) addiction has been reported in many cancers including malignant adult gliomas. Glutamine likely promotes cancer cell proliferation and survival likely through generation of the TCA cycle intermediate alpha-ketoglutarate (α-KG). Importantly, α-KG is a critical co-factor for histone lysine demethylases including JMJD3, the enzyme responsible for removing the methyl groups from H3K27me3. Our preliminary data shows H3K27M tumor cells require Gln for survival, and if Gln is removed from the culture media, cells can be rescued by the addition of α-KG. Furthermore, Gln deprivation leads to an increase in H3K27 trimethylation similar to direct inhibition of JMJD3. It is for these reasons we hypothesize that H3K27M tumors are dependent on Gln derived α-KG both for feeding the TCA cycle and for further decreasing H3K27 trimethylation. Inhibition of Gln metabolism will likely uncover novel therapeutic targets for this deadly disease. In Aim 1 we will study Gln and glucose metabolism in H3K27M tumor cells and compare this to Wild Type (WT) tumors and Embryonic Stem Cells (ESCs). In Aim 2 we will validate the therapeutic validity of inhibiting Gln metabolism in H3K27M tumors. |
| Institute: | Mayo Clinic |
| Last Name: | Daniels |
| First Name: | David |
| Address: | 200 First Street SW Rochester, MN 55905 |
| Email: | daniels.david@mayo.edu |
| Phone: | 507-284-2511 |
Summary of all studies in project PR000684
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001023 | H3K27M cells and glutamine metabolomics 1 million cell test (part-I) | Homo sapiens | Mayo Clinic | MS | 2020-07-15 | 1 | 4 | Not available |
| ST001024 | TCA cycle metabolomics of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate (Part-II) | Homo sapiens | Mayo Clinic | MS | 2020-07-15 | 1 | 36 | Not available |
| ST001025 | TCA Isotopmer metabolomics of H3K27M Cells grown in regular media, glutamine enriched regular media, and glucose encriched regular media (Part-III) | Homo sapiens | Mayo Clinic | MS | 2020-07-15 | 1 | 114 | Not available |
| ST001026 | TCA cycle metabolomics of H3K27M Cell Nucleus Fraction and Cell Mitonchonrdial Fraction (Part-IV) | Homo sapiens | Mayo Clinic | MS | 2020-07-15 | 1 | 36 | Not available |
