The proposal focuses on molecular mechanisms of oncogenesis. It includes three major projects. The first deals with lncRNAs (long non-coding RNAs) that are specifically regulated by the oncoprotein MYC and by the oncogenic H1047R mutant of p110a of PI3K (phosphatidylinositol 3-kinase). The second focuses on the application of a novel and quantitative proteomic technique, QBID, to determine stimulus-specific changes in the interactomes in the PI3K pathway. The third project consists of a structural analysis of the p110-p85 complex of PI3K. Each of these projects is highly and directly cancer-relevant. Progress on these fronts will have an impact on the translation of basic knowledge into clinical medicine.
The application proposes three projects, one on oncoprotein-regulated lncRNAs, a second on the application of a novel and quantitative proteomic technique to the analysis of stimulus-specific interactomes in the PI3K pathway, and a third launching a cryoEM analysis of the structure of the PI3K heterodimer.
|Ito, Yoshihiro; Hart, Jonathan R; Vogt, Peter K (2018) Isoform-specific activities of the regulatory subunits of phosphatidylinositol 3-kinases - potentially novel therapeutic targets. Expert Opin Ther Targets 22:869-877|
|Jacob, Nicholas T; Miranda, Pedro O; Shirey, Ryan J et al. (2018) Synthetic molecules for disruption of the MYC protein-protein interface. Bioorg Med Chem 26:4234-4239|
|Ito, Yoshihiro; Vogt, Peter K; Hart, Jonathan R (2017) Domain analysis reveals striking functional differences between the regulatory subunits of phosphatidylinositol 3-kinase (PI3K), p85? and p85?. Oncotarget 8:55863-55876|
|Balatti, Veronica; Nigita, Giovanni; Veneziano, Dario et al. (2017) tsRNA signatures in cancer. Proc Natl Acad Sci U S A 114:8071-8076|