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 #
5R00CA154887-04
Application #
8548103
Study Section
Special Emphasis Panel (NSS)
Program Officer
Spalholz, Barbara A
Project Start
2012-07-30
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$234,059
Indirect Cost
$15,696
Name
University of California Merced
Department
Type
Schools of Earth Sciences/Natur
DUNS #
113645084
City
Merced
State
CA
Country
United States
Zip Code
95343
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
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
Edwards, Lauren; Gupta, Rohit; Filipp, Fabian Volker (2016) Hypermutation of DPYD Deregulates Pyrimidine Metabolism and Promotes Malignant Progression. Mol Cancer Res 14:196-206
Tiffen, Jessamy C; Gunatilake, Dilini; Gallagher, Stuart J et al. (2015) Targeting activating mutations of EZH2 leads to potent cell growth inhibition in human melanoma by derepression of tumor suppressor genes. Oncotarget 6:27023-36
Zielinski, Daniel C; Filipp, Fabian V; Bordbar, Aarash et al. (2015) Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis. Nat Commun 6:7101
Filipp, Fabian V (2013) A Gateway between Omics Data and Systems Biology. J Metabolomics Syst Biol 1:1
Filipp, Fabian V (2013) Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator. J Carcinog 12:14
Filipp, Fabian V; Scott, David A; Ronai, Ze'ev A et al. (2012) Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells. Pigment Cell Melanoma Res 25:375-83
Filipp, Fabian V; Ratnikov, Boris; De Ingeniis, Jessica et al. (2012) Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanoma. Pigment Cell Melanoma Res 25:732-9

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