Theresa Vincent, PhD

Nearly ninety percent of all cancer patient deaths are due to metastasis. Our research focuses on the process when tumor cells migrate from the tumor to blood and lymph vessels where they can spread to other parts of the body. Our goal is a better understanding of the complex mechanisms behind metastasis so that our results in the long term can be applied in the clinic.

Identification of Cellular Events that Affect Metastasis

While remarkable advances have been made in the treatment of primary breast cancer, breast cancer metastasis remains largely incurable and is what accounts for approximately 90 percent of patient deaths. Metastatic breast cancer cells can invade both lymphatic and blood vessels and spread to distant organs such as the lungs, liver, brain, and bone, and these cancer cells remain resistant to conventional breast cancer treatments such as chemotherapy and anti-estrogen therapies. Thus, patients diagnosed with metastatic disease have extremely poor outcomes, with only 5 to 10 percent of patients surviving 10 years after initial diagnosis. Despite extensive studies over the last four decades, there are no therapies that can be said to be curative of breast cancer metastasis, and therefore there has been little improvement in the survival of patients with breast cancer metastasis. New treatment approaches are urgently needed both to aggressively treat primary cancers before metastasis and metastasis once it has occurred.

As tumors progress towards advanced stages they dedifferentiate, become more aggressive, and lose the characteristics of the original tissue. They also acquire the migratory capacity that allows the tumor to spread or metastasize to distant sites in the body, eventually causing patient death. For epithelial tumors to metastasize the tumor cells undergo a cell plasticity program known as the epithelial-to-mesenchymal transition (EMT), which allows the cells to develop migratory and invasive abilities. During EMT, cells also lose their proliferative capacity and become more stem-like. This remarkable transition leads to both increased invasiveness and the ability to evade numerous cancer treatments including hormonal therapies. Our main interest is to now gain a better understanding of the cellular changes that induce and drive tumor cell plasticity.

Toward this aim our investigations have identified a novel central driving feature of the EMT program which is highly druggable, specifically that EMT is accompanied by a dramatic and essential reprogramming of ribosome biogenesis, the key step in the creation of the protein synthesis machinery, the ribosome. Although ribosome biogenesis is a canonical hallmark of cell growth and proliferation, our studies demonstrated that ribosome biogenesis in non-dividing metastatic cancer cells is essential for their viability, metastasis, and the survival of established metastases.
 
Until recently, ribosomes have been considered to play only passive roles during the production of proteins. Our studies suggest the contrary and are therefore directed toward understanding the more complex and active roles of how ribosomes and translation control contribute to cell physiology in health and disease states.
 
The Importance of Collaboration

Currently, we have several ongoing national and international research projects within these areas and our laboratory places a special focus on international collaborative efforts. It is our ambition to create a unique laboratory and educational environment that is not limited by departmental or national barriers but only by our scientific education, curiosity, and ambition.