To understand how neoplastic cells adapt to stresses commonly encountered in solid and hematopoietic malignancies, it is critical to establish how cells alter their metabolism in order to survive these stresses. The purpose of the Metabolism Core is to provide support to the Project Leaders for analyses of cellular metabolism under specific stresses that reflect the unique features of tumor environments: specifically, growth factor withdrawal, nutrient and/or oxygen depletion. The core will provide advice, training, and access to equipment and reagents essential to these inquiries. The core will provide assistance with assays for glucose uptake, glycolysis, NADH and NADPH production, oxygen consumption, and mitochondrial function. Many of the proposed experiments also depend on the use of customized work stations and CO2 incubators for cell culture under hypoxic and/ or anoxic conditions. Furthermore, sucrose gradient centrifugation for polysome profiling will be supervised by a research technician within the core. Therefore, the core will maintain and support the following equipment: A. oxymeter, B. fluorometer, C. hypoxia hoods and specialized hypoxia C02 incubators, D. gradient makers and rotors for sucrose gradient centrifugation. Funds for a second oxymeter, and an anoxia workstation capable of achieving O2 levels_<0.01 % O2, are also requested. The core director, Dr. Brian Keith, will supervise a research specialist in these endeavors. Both core personnel have multiple publications in the areas of cellular bioenergetics, hypoxia and metabolism. The goal of this core is to provide equipment shared by all three research programs and train research associates, postdoctoral fellows, graduate students, and technicians in the techniques described.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Li, Bo; Qiu, Bo; Lee, David S M et al. (2014) Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature 513:251-5
Mathew, Lijoy K; Skuli, Nicolas; Mucaj, Vera et al. (2014) miR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma. Proc Natl Acad Sci U S A 111:291-6
Maas, Nancy L; Singh, Nickpreet; Diehl, J Alan (2014) Generation and characterization of an analog-sensitive PERK allele. Cancer Biol Ther 15:1106-11
Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J et al. (2014) Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510:298-302
Mathew, Lijoy K; Lee, Samuel S; Skuli, Nicolas et al. (2014) Restricted expression of miR-30c-2-3p and miR-30a-3p in clear cell renal cell carcinomas enhances HIF2* activity. Cancer Discov 4:53-60
Cheong, Heesun; Wu, Junmin; Gonzales, Linda K et al. (2014) Analysis of a lung defect in autophagy-deficient mouse strains. Autophagy 10:45-56
Ye, Jiangbin; Fan, Jing; Venneti, Sriram et al. (2014) Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov 4:1406-17
Ackerman, Daniel; Simon, M Celeste (2014) Hypoxia, lipids, and cancer: surviving the harsh tumor microenvironment. Trends Cell Biol 24:472-8
Chitnis, Nilesh; Pytel, Dariusz; Diehl, J Alan (2013) UPR-inducible miRNAs contribute to stressful situations. Trends Biochem Sci 38:447-52
Wong, Waihay J; Qiu, Bo; Nakazawa, Michael S et al. (2013) MYC degradation under low O2 tension promotes survival by evading hypoxia-induced cell death. Mol Cell Biol 33:3494-504

Showing the most recent 10 out of 52 publications