|Institution||College of Medicine|
|Department||Cellular and Molecular Physiology|
|Address||500 University Drive Hershey PA 17033|
Associate Professor of Cellular and Molecular Physiology
SECONDARY APPOINTMENT(S)/ INSTITUTE(S)/ CENTER(S):
Penn State Hershey Cancer Institute
GRADUATE PROGRAM AFFILIATIONS:
Cellular and Molecular Physiology, Biomedical Sciences, MD/PhD Degree Program
B.S. University of Scranton, 1984
Ph.D., Johns Hopkins University School of Medicine, 1989
Our long-term goal is to better understand the molecular signaling cascades involved in non-melanoma skin carcinogenesis (NMSC) in order to identify novel therapeutic targets. NMSC is the most common form of human cancer, and estimates suggest that over 1.5 million new cases of skin cancer will be diagnosed this year. Although most skin cancers are easily treated, a sub-population of people are at higher risk, and about 10,000 Americans a year die from skin cancer. An increasing number of these people have received organ transplants. Because transplant patients take immunosuppressive drugs, they are at a much higher risk for the development of cancers in general and skin cancer in particular. With the increasing number of organ transplant recipients, targets for therapy and prevention of skin cancer will become even more important. Our research focuses on the polyamine pathway and mTOR-dependent pathways in early skin cancer development. There is strong experimental evidence indicating the location of epidermal stem cells that are modified by carcinogen exposure is in the hair follicle bulge. By directing expression of transgenes to this region of the epidermis, we can modify gene expression in stem cells and ask what effect these genetic alterations have on tumor development. Using transgenic models, we were the first to show a link between induction of the Raf/MEK/ERK pathway and increased ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis, in skin tumors. Importantly, we have established that high ODC activity is a necessary component of MEK-induced skin tumor development, and both antizyme (AZ), which binds to ODC and causes it to be degraded, and DFMO, a suicide inactivator of ODC, are a powerful suppressors of these tumors. Current work explores the role of mTOR-dependent pathways in skin carcinogenesis in response to both chemical carcinogens and UV light using mice with conditional deletion of mTOR, the mTORC1 component raptor, or the mTORC2 component rictor.
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