Grants and Contracts Details


Transfer Proposal - Specific Aims -The specific aims have not been modified. Studies and Results - We have initiated studies proposed in all three specific aims. In Specific Aim 1, we proposed to investigate the degradation of PHLPP by ubiquitination. A significant progress has been made in addressing the questions in the proposal. We have found that the SCFbeta-Trcp mediated ubiquitination and degradation of PHLPP1 is phosphorylation dependent. In addition, the potential phosphorylation sites on PHLPP1 have been identified. We are in the process of preparing a manuscript to report our findings. In Specific Aim 2, we proposed to elucidate the role of PHLPP in regulating cell polarity. We have started to generate stable knockdown cell lines using Cac02 cells. We are in the process of optimizing the migration and polarization assays in the lab. In Specific Aim 3, we proposed to study the physiological function of PHLPP in intestine homeostasis and tumorigenesis using mouse models. Preliminary studies have been performed to isolate the GI tissues from the Wild-type and PHLPP1 knockout mice. Immunohistochemical stai'ning experiments were conducted to compare the phenotypical differences. Since we started the new lab in the University of Kentucky, our collaborator, Dr. Alexandra Newton, has agreed to transfer more PHLPP knockout mice to us. We are in the process of getting the animals transferred. Significance . Colorectal cancer represents one of the most prevalent malignancies in both men and women. However, ultimately, approximately half of all diagnosed coJorectal cancer patients will develop disseminated advanced disease, which in most cases will be fatal due to poor responses to available treatment options. Thus, the development of more novel therapeutic targets is required to further improve the survival rate. PHLPP represents a novel family of protein phosphatase and tumor suppressor. Our preliminary studies have established the initial link between PHLPP and colon cancer. The results from proposed studies will aid in developing novel therapeutic strategies in cancer treatment by using PHLPP as a target.
Effective start/end date4/1/0911/30/14


  • National Cancer Institute: $1,710,434.00


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