Abstract

Aim 1: Develop and Implement High-Throughput Kinase Assays for Monitoring the Signaling Response to DNA Damage.
Aim 2 : Monitor Kinase Localization, Cell Cycle Progression, and Apoptosis in Response to DNA Damage.
Aim 3 : Construct a Quantitative Predictive Systems Biology Model for Protein Kinase Network Responses During DNA Damage Signaling.
Aim 4. Utilize Knock-Out Mutant Analysis, shRNA Technologies, and Genetic Engineering in Cells and Mice to Test Hypotheses Generated from the Model and to Further Probe DNA Damage Signaling Networks.
Aim 5 - Discovery of New Kinase Substrates that Play Key Roles in the DNA Damage Response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA112967-03
Application #
7286769
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2006
Total Cost
$367,891
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Kulkarni, Madhura; Tan, Tuan Zea; Syed Sulaiman, Nurfarhanah Bte et al. (2018) RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer. Oncotarget 9:14175-14192
Miller, Miles A; Sullivan, Ryan J; Lauffenburger, Douglas A (2017) Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and Monitoring of Cancer. Clin Cancer Res 23:623-629
Nagel, Zachary D; Kitange, Gaspar J; Gupta, Shiv K et al. (2017) DNA Repair Capacity in Multiple Pathways Predicts Chemoresistance in Glioblastoma Multiforme. Cancer Res 77:198-206
Oudin, Madeleine J; Barbier, Lucie; Schäfer, Claudia et al. (2017) MENA Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer. Mol Cancer Ther 16:143-155
Bruno, Peter M; Liu, Yunpeng; Park, Ga Young et al. (2017) A subset of platinum-containing chemotherapeutic agents kills cells by inducing ribosome biogenesis stress. Nat Med 23:461-471
Werbin, Jeffrey L; Avendaño, Maier S; Becker, Verena et al. (2017) Multiplexed Exchange-PAINT imaging reveals ligand-dependent EGFR and Met interactions in the plasma membrane. Sci Rep 7:12150
White, Forest M; Wolf-Yadlin, Alejandro (2016) Methods for the Analysis of Protein Phosphorylation-Mediated Cellular Signaling Networks. Annu Rev Anal Chem (Palo Alto Calif) 9:295-315
Wilson, Jennifer L; Dalin, Simona; Gosline, Sara et al. (2016) Pathway-based network modeling finds hidden genes in shRNA screen for regulators of acute lymphoblastic leukemia. Integr Biol (Camb) 8:761-74
Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A (2016) Modeling Tumor Clonal Evolution for Drug Combinations Design. Trends Cancer 2:144-158
Tuncbag, Nurcan; Milani, Pamela; Pokorny, Jenny L et al. (2016) Network Modeling Identifies Patient-specific Pathways in Glioblastoma. Sci Rep 6:28668

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