Development of a technology strategy for the State of Tennessee. CRADA final report

The Department of Energy supports and continues to lead in cultivating new initiatives in federal-state partnerships. The resources and capabilities of the DOE facilities should be used to enhance the economic growth of the US and the states have demonstrated expertise and commitment to economic development. DOE seeks to assure that the principal economic benefits of its collaboration with the private sector flow to the US taxpayer. Specifically, under US Code, Title 15, Chapter 53, federal laboratories should provide means of access to scientific and technological developments (Section 3701) and provide technical assistance to state and local government officials (Section 3710). The Department of Economic and Community Development (ECD) has the responsibility in Tennessee to provide the technological vision and leadership required for long-term growth and prosperity for the state in the global marketplace. Through the sponsorship of new and innovative programs in assisting existing industry, fostering endeavors in research and development, and aggressive pursuit of federally-sponsored development programs, ECD seeks to advance the State`s competitive position, enhance the State`s ability to foster new business growth and meet the economic and security needs of the State`s citizens. ECD has found that collaborations with Lockheed Martin Energy Research Corporation, and the DOE operations located in Oak Ridge, Tennessee, significantly benefits the State. ECD has created a senior executive advisory group for the Commissioner and developed plans to establish a high technology office for the State. Energy Research and ECD believe that their common interests and goals create a unique opportunity to demonstrate the commitment to America`s economic leadership. Increased collaboration will be created for developing a technology strategy for Tennessee, employing technological advantages in the State, and advancing the implementation of technology in the private sector

Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival

The efficacy of prospective cancer treatments is routinely estimated by in vitro cell-line proliferation screens. However, it is unclear whether tumor aggressiveness and patient survival are influenced more by the proliferative or the migratory properties of cancer cells. To address this question, we experimentally measured proliferation and migration phenotypes across more than 40 breast cancer cell-lines. Based on the latter, we built and validated individual predictors of breast cancer proliferation and migration levels from the cells' transcriptomics. We then apply these predictors to estimate the proliferation and migration levels of more than 1000 TCGA breast cancer tumors. Reassuringly, both estimates increase with tumor's aggressiveness, as qualified by its stage, grade, and subtype. However, predicted tumor migration levels are significantly more strongly associated with patient survival than the proliferation levels. We confirmed these findings by conducting siRNA knock-down experiments on the highly migratory MDA-MB-231 cell lines and deriving gene knock-down based proliferation and migration signatures. We show that cytoskeletal drugs might be more beneficial in patients with high predicted migration levels. Taken together, these results testify to the importance of migration levels in determining patient survival.Toxicolog

Integrin-mediated Tyrosine Phosphorylation of Shc in T Cells Is Regulated by Protein Kinase C-dependent Phosphorylations of Lck

Integrin receptor signals are costimulatory for mitogenesis with the T-cell receptor during T-cell activation. A subset of integrin receptors can link to the adapter protein Shc and provide a mitogenic stimulus. Using a combination of genetic and pharmacological approaches, we show herein that integrin signaling to Shc in T cells requires the receptor tyrosine phosphatase CD45, the Src family kinase member Lck, and protein kinase C. Our results suggest a model in which integrin-dependent serine phosphorylation of Lck is the critical step that determines the efficiency of Shc tyrosine phosphorylation in T cells. Serine phosphorylation of Lck is dependent on PKC and is also linked to CD45 dephosphorylation. Mutants of Lck that cannot be phosphorylated on the critical serine residues do not signal efficiently to Shc and have greatly reduced kinase activity. This signaling from integrins to Lck may be an important step in the costimulation with the T-cell receptor during lymphocyte activation