This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Eight years ago, Aurora kinase A was classified as an oncogene. This protein has been found at high levels in many forms of cancer, including gastric, colorectal, breast, esophageal and lung cancers ?indeed, as many as 86% of lung cancers exhibit inappropriate expression of Aurora A. Simply overexpressing this kinase can transform certain normal cells into tumors. Importantly, tumors generated by high Aurora A kinase activity demonstrate increased resistance to drugs that target microtubule formation, including Taxol. In fact, clinical trials are currently underway for small molecule inhibitors of Aurora kinase activity in treating cancer. However, very little is known about the molecular targets of this kinase. How does this transformation occur? Are proteins outside of the normal function of Aurora A involved in this process? It is the goal of the current proposal to tap into the combined power of high performance mass spectrometry, quantitative strategies in proteomics, and selective phosphopeptide enrichment methods to comprehensively characterize substrates of Aurora A kinase, on a proteome-wide scale. This information is a critical foundation from which we can begin to understand how unregulated Aurora A kinase activity causes lung cancer, and how to treat it.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018787-09
Application #
8359702
Study Section
Special Emphasis Panel (ZRR1-RI-6 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
9
Fiscal Year
2011
Total Cost
$259,559
Indirect Cost
Name
Dartmouth College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
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