Office of Research: Faculty

Dr. David Crowe

The ends of our chromosomes (telomeres) shorten each time our cells divide. Therefore as we age our telomeres become shorter, normally leading our cells to stop dividing. Our telomere length is set early during development, but cellular stresses such as tobacco use and sun exposure can shorten telomeres. Short telomeres have been associated with a variety of age related diseases including cancer. The reverse transcriptase telomerase can extend the ends of chromosomes resulting in increased cellular lifespan, which is important for highly proliferative tissues such as mucosa, epidermis, and bone marrow. However, most cancer cells also express telomerase which promotes progression of tumors. Our laboratory has shown that premalignant cells short circuit a key mechanism by which mucosal cells differentiate leading to increased telomerase expression. We also have shown that head and neck cancers with short telomeres are significantly associated with metastasis, which results in poor prognosis for these patients. These metastatic cells have characteristics of cancer stem cells, which are critical for initiating tumors at these distant sites. Using a variety of transgenic models and patient tumor tissues, our laboratory is engaged in understanding how mucosal stem cells regulate their telomere length and how disrupted telomere maintenance can lead to tumor formation and metastasis.