New targeted therapies for breast cancer are needed for patients who do not haveindication for targeted therapy (e.g:trastuzumab) in HER2 and/or ER negative tumors.The candidate has a strong background in basic and translational research in cancer biology and molecular therapeutics. She has shown that PEA-15, a novelphosphoprotein, has tumor suppressor properties; binds to ERK, blocking ERKactivation. Her long-term goal is to be a independent translational researcher and to usetargeted therapies to improve treatment options for patients with breast cancer. Tobecome independent, she requires additional training in 5 areas: (1) training inInvestigational New Drug (IND) and Patent applications to translate laboratory researchinto hypothesis-driven clinical trials; (2) identification of mouse models with most efficientknockdown using siRNA (3) metastasis assays, epithelial-to-mesenchymal transition(EMT) and angiogenesis; and (4) training in leadership skills. She has identified highlyexperienced co-mentors who are committed to helping her develop her skills in theseareas. One is an expert in developing novel targeted therapies and the other hasdeveloped a novel liposomal in vivo siRNA delivery system. The primary objective is todefine the role of ERK in HER2-negative breast cancer, and to develop ERK as atherapeutic target. The central hypothesis is that suppressing ERK reducestumorigenicity and metastasis in breast cancer. The 3 specific aims are: (1) Determinewhether suppressing ERK inhibits tumorigenicity in HER2-negative breast cancer cells.(2) Determine the impact of ERK inhibition on EMT in HER2-negative breast cancer cells(3) Determine the role of the ERK modulator PEA-15 in HER2-negative breast cancer.Three different approaches will be used to suppress ERK: siRNA to knock down ERK,PEA-15 gene therapy to sequester ERK, and treatment with an inhibitor of MEK, whichlies upstream of ERK. At the conclusion, she will determine if ERK pathway would be auseful molecular target for treatment of such disease. The candidate will use herextensive training to pursue independent research on ERK modulator resistance intumorigenicity/metastasis, and development preclinical data which will lead to ERKtargeted clinical trials in breast cancer.