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 #
5U54CA149147-04
Application #
8517446
Study Section
Special Emphasis Panel (ZCA1-SRLB-C)
Project Start
Project End
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$852,528
Indirect Cost
$412,652
Name
Georgetown University
Department
Type
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Cook, Katherine L; Soto-Pantoja, David R; Clarke, Pamela A G et al. (2016) Endoplasmic Reticulum Stress Protein GRP78 Modulates Lipid Metabolism to Control Drug Sensitivity and Antitumor Immunity in Breast Cancer. Cancer Res 76:5657-5670
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
Bhuvaneshwar, Krithika; Belouali, Anas; Singh, Varun et al. (2016) G-DOC Plus - an integrative bioinformatics platform for precision medicine. BMC Bioinformatics 17:193
(2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12:1-222
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
Beck, Tim N; Korobeynikov, Vladislav A; Kudinov, Alexander E et al. (2016) Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer. Cell Rep 16:657-71
Zhang, Y-W; Nasto, R E; Varghese, R et al. (2016) Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation. Oncogene 35:1643-56
Bhuvaneshwar, Krithika; Sulakhe, Dinanath; Gauba, Robinder et al. (2015) A case study for cloud based high throughput analysis of NGS data using the globus genomics system. Comput Struct Biotechnol J 13:64-74
Shi, Xu; Barnes, Robert O; Chen, Li et al. (2015) BMRF-Net: a software tool for identification of protein interaction subnetworks by a bagging Markov random field-based method. Bioinformatics 31:2412-4
Dabydeen, Sarah A; Kang, Keunsoo; Díaz-Cruz, Edgar S et al. (2015) Comparison of tamoxifen and letrozole response in mammary preneoplasia of ER and aromatase overexpressing mice defines an immune-associated gene signature linked to tamoxifen resistance. Carcinogenesis 36:122-32

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