BREAST CANCER The Role of Protein Tyrosine Kinases and Polyamine Metabolism Normal growth and development requires that every cell in the body respond appropriately to the many signals it receives from its environment - these signals include both circulating hormones as well as positional information conveyed by the structural milieu surrounding the cell. The cell's processing of this information (known as signal transduction) is frequently disrupted in cancer.
The long term interest of my laboratory is understanding the molecular mechanisms that govern the highly complex but exquisitely orchestrated processes of normal growth and development, and how these processes are disrupted in disease states such as cancer
The major research focus of my laboratory is breast cancer - the most commonly diagnosed cancer in American women. Unfortunately the biochemical pathways altered in breast cancer remain poorly defined. We are particularly interested in two distinct pathways: signal transduction activated by the protein tyrosine kinases HER2 and SRC, and polyamine metabolism regulated by ornithine decarboxylase and its natural regulator antizyme.
HER2, the target of the breast cancer drug Herceptin® is critical for continued growth of a substantial fraction of breast cancers. SRC is suspected to also be important in breast cancer growth, although its exact role remains to be defined. My laboratory's current efforts to understand the role of HER2 and SRC in breast cancer employ a novel, 3-dimentional culture system that, unlike traditional culture systems, allows normal breast epithelial cells to differentiate. It is our belief that this more physiological system will ultimately allow us to understand the roles of HER2 and SRC in breast cancer, and identify critical targets for future drug development.
Increased polyamine levels due to increased ornithine decarboxylase activity is a frequent occurrence in breast cancer. We are using transgenic mouse models to determine if increased antizyme expression can decrease breast cancer growth, and even reduce breast cancer incidence. If successful, this would define antizyme as a novel target for breast cancer therapeutic drugs. | 
