The project seeks to understand the role of pyruvate kinase as regulator of cancer metabolism. Insight into glycolytic and TCA cycle flux from metabolic profiles of cancer cell lines will reveal new drug targets and generate new regimes for diagnosis and treatment of cancer patients.

Public Health Relevance

The impact of this study is extremely high;this work could entirely change the field of cancer metabolism. I will provide a platform to study the complex network of central carbon metabolism with the possibility to follow changes upon tumor progression or perturbation by interference with drugs or molecular biology tools. The work proposed brings mechanistic insights into a key regulator of the tumor metabolome and paves the way to diagnose and treat not only mammary gland but also numerous other carcinomas

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
4R00CA154887-03
Application #
8525754
Study Section
Special Emphasis Panel (NSS)
Program Officer
Spalholz, Barbara A
Project Start
2012-07-30
Project End
2015-07-31
Budget Start
2012-09-19
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$248,999
Indirect Cost
$16,185
Name
University of California Merced
Department
Type
Schools of Earth Sciences/Natur
DUNS #
113645084
City
Merced
State
CA
Country
United States
Zip Code
95343
Olmstead, Keedrian I; La Frano, Michael R; Fahrmann, Johannes et al. (2017) Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance. Metabolomics 13:
Singh, Simar J; Turner, William; Glaser, Drew E et al. (2017) Metabolic shift in density-dependent stem cell differentiation. Cell Commun Signal 15:44
Filipp, Fabian V (2017) Crosstalk between epigenetics and metabolism-Yin and Yang of histone demethylases and methyltransferases in cancer. Brief Funct Genomics 16:320-325
Filipp, Fabian V (2017) Precision medicine driven by cancer systems biology. Cancer Metastasis Rev 36:91-108
Lanning, Nathan J; Castle, Joshua P; Singh, Simar J et al. (2017) Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities. Cancer Metab 5:6
Wilson, Stephen; Fan, Lingling; Sahgal, Natasha et al. (2017) The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells. Oncotarget 8:30328-30343
Wilson, Stephen; Qi, Jianfei; Filipp, Fabian V (2016) Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines. Sci Rep 6:32611
Tiffen, Jessamy; Wilson, Stephen; Gallagher, Stuart J et al. (2016) Somatic Copy Number Amplification and Hyperactivating Somatic Mutations of EZH2 Correlate With DNA Methylation and Drive Epigenetic Silencing of Genes Involved in Tumor Suppression and Immune Responses in Melanoma. Neoplasia 18:121-32
Tiffen, Jessamy C; Gallagher, Stuart J; Tseng, Hsin-Yi et al. (2016) EZH2 as a mediator of treatment resistance in melanoma. Pigment Cell Melanoma Res 29:500-7
Edwards, Lauren; Gupta, Rohit; Filipp, Fabian Volker (2016) Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression. Mol Cancer Res 14:196-206

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