Endocrine Responsiveness and Cellular Stress. We have identified novel signaling through the unfolded protein response (UPR) that is inifiated by an endocrine therapy-induced endoplasmic reficulum stress, with signaling further integrated through the mitochondria and nucleus. Dr. Clarke and his team will model the effects of this signaling on the function of these organelles and their respecfive roles in determining cell fate as affected by ER acfion. We will use a panel of novel cell lines, many of which we isolated [8-10,35- 42]. Inifial seed genes, e.g., API [10], BCL2 [32,33], BCL3 [49], BCLW (and other BCL2 family members), CAV1 [50], ERa [51], ERRy [10], IRF1 [27,31,52], NFKB [27,33], NPM1 [27-29], and XBP1 [27,32] will be used to initiate computational modeling of endocrine-related cell stress signals. We will extend this signaling network by including other genes known to affect endoplasmic reticulum and mitochondrial funcfion, incorporafing new targets as implicated by the functional genomics in Project 2 and the rodent studies in Project 3.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA149147-05
Application #
8627140
Study Section
Special Emphasis Panel (ZCA1-SRLB-C)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
$805,497
Indirect Cost
$321,205
Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
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Beck, Tim N; Smith, Chad H; Flieder, Douglas B et al. (2017) Head and neck squamous cell carcinoma: Ambiguous human papillomavirus status, elevated p16, and deleted retinoblastoma 1. Head Neck 39:E34-E39
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Chen, Xi; Jung, Jin-Gyoung; Shajahan-Haq, Ayesha N et al. (2016) ChIP-BIT: Bayesian inference of target genes using a novel joint probabilistic model of ChIP-seq profiles. Nucleic Acids Res 44:e65
Cook, Katherine L; Schwartz-Roberts, Jessica L; Baumann, William T et al. (2016) Linking autophagy with inflammation through IRF1 signaling in ER+ breast cancer. Mol Cell Oncol 3:e1023928
Beck, Tim N; Golemis, Erica A (2016) Genomic insights into head and neck cancer. Cancers Head Neck 1:

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