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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA104838-09
Application #
8382061
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
9
Fiscal Year
2012
Total Cost
$131,333
Indirect Cost
$48,265
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Xu, Zhenhua; Bu, Yiwen; Chitnis, Nilesh et al. (2016) miR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis. Nat Commun 7:11422
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Gade, Terence P F; Hunt, Stephen J; Harrison, Neil et al. (2015) Segmental Transarterial Embolization in a Translational Rat Model of Hepatocellular Carcinoma. J Vasc Interv Radiol 26:1229-37
Qiu, Bo; Ackerman, Daniel; Sanchez, Danielle J et al. (2015) HIF2α-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma. Cancer Discov 5:652-67
Ye, Jiangbin; Palm, Wilhelm; Peng, Min et al. (2015) GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev 29:2331-6
Mucaj, V; Lee, S S; Skuli, N et al. (2015) MicroRNA-124 expression counteracts pro-survival stress responses in glioblastoma. Oncogene 34:2204-14

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