Dr. Angela Tyner
I have been a faculty member at the University of Illinois College of Medicine for over 20 years, where I have mentored 17 Ph.D. students and 15 postdoctoral researchers in my laboratory, as well as high school students and undergraduates. Many of my trainees have gone on to productive careers in academia, medicine and industry. I have had a long-standing interest in epithelial biology, signaling, and cancer in the gastrointestinal tract, prostate, and breast. Current research in my laboratory focuses on the intracellular epithelial tyrosine kinase Protein Tyrosine Kinase 6 (PTK6, also referred to as the Breast Tumor Kinase BRK, or the SRC-related Intestinal Kinase Sik). My laboratory was the first to clone PTK6 from normal cells. PTK6 is expressed in differentiated epithelial cells in the small and large intestine, and in prostate epithelial cells. PTK6 is induced in a majority of human breast tumors, and it is highly expressed in invasive breast cancer. We developed the Ptk6 null mouse model, which has defects in intestinal epithelial cell differentiation and apoptosis in response to DNA damage. We found that Ptk6 null mice are resistant to carcinogen induced colon cancer. We determined that PTK6 is expressed in the normal prostate, where it is localized to epithelial cell nuclei. However in prostate cancers, nuclear PTK6 is lost, and in some human and mouse prostate tumors, endogenous PTK6 is activated at the plasma membrane. Our data indicate that active membrane-associated PTK6 promotes the epithelial mesenchymal transition (EMT) and cell transformation in prostate cancer. Recently, we found that PTK6 is also activated at the plasma membrane in mammary gland tumors, and it plays an essential role in ERBB2 induced tumorigenesis in a mouse model of breast cancer. Understanding mechanisms of PTK6 signaling and its contributions to tumorigenesis could lead to the development of new cancer-fighting drugs. In addition, the membrane association of active PTK6 may serve as a marker for tumors that require more aggressive treatment.