Career Goal and Training/Research Plan: My long-term career goal is to become an influential scientist in the field of breast cancer research and to make discoveries that will significantly improve the survival and quality of life for cancer patients. I chose Princeton University to pursue my graduate study because of the high academic standard and the multidisciplinary nature of the training program offered here. I chose Dr. Yibin Kang as my mentor, who is using innovative strategies and advanced technologies to tackle the most daunting problem in cancer research -- the metastatic spread of breast cancer. The excellent and passionate mentorship of Dr. Kang has resulted in several prestigious fellowships being awarded to members of the lab. My thesis committee consists of four leading scholars in their fields of research, all of which are relevant to my study on breast cancer metastasis. Our laboratory is affiliated with the Molecular Biology Department, the Lewis Sigler Institute of Integrative Genomics, and the Cancer Institute of New Jersey (CINJ), and maintains active collaborations with oncologists in CINJ, the University of Michigan, and other leading medical institutions. In addition, our collaborations with major pharmaceutical companies such as Eli Lilly, Merck, and Amgen provide us with access to experimental drugs and expertise necessary for translational metastasis research. Active participation of our lab in the Breast Cancer Program of CINJ and my regular attendance at international cancer research conferences will further broaden my experience in the clinical and translational aspects of breast cancer research. I believe such a comprehensive and multidisciplinary training environment at Princeton will allow me develop into a highly competent scientist at the forefront of breast cancer research.

Most breast cancer fatalities are caused by the metastatic spread of tumor cells to distant organs, a process that relies heavily on the interaction between cancer cells and their host tissue environment (stroma). As such, these interactions may represent the Achilles' heel of metastatic cancer and are ideal targets for anti-metastasis therapeutics. However, current tools do not allow real-time detection of tumor-stroma interactions, which makes it difficult to assess what pathways are crucial for metastasis initiation and maintenance, when and where these pathways are active, and thus how targeted therapies against these pathways should be applied. To overcome this limitation, we have developed a novel mouse model to detect and control crucial tumor-stroma signaling pathways in real-time. We will use this novel technology to determine whether signaling activity mediated by transforming growth factor-beta (TGF-beta), a cytokine that has been implicated for breast cancer metastasis, may be important for tumor malignancy at different stages and organ location of metastasis. We will also use this mouse model to test the efficacy of pharmaceutical agents in disrupting this signaling pathway.

Applicability: Our novel mouse model will help us understand the temporal-spatial requirement of TGF-beta signaling in breast cancer metastasis. This research will potentially enhance the accuracy of targeted therapies and will benefit those patients harboring metastatic lesions that require TGF-beta signaling. Our in vivo assay system can drastically reduce the time needed to characterize preclinical drugs, increase their success rate, and accelerate the pace at which they enter the market. Judged from the enormous interest of the pharmaceutical community in our novel system and the success of our preliminary studies, I expect our results to influence clinical application within 2-3 years.