Department of Biomedical Sciences: Professor
Molecular Mechanisms of Carcinogenesis Program: Director
Lab Technicians: Jodi Yanagida and Brianna Hammiller
Graduate Students: Kyle Bichsel, Jenan Al-Matouq, and Nitin Marwaha
Dave, Becca (graduated with her M.S.), Dr. Hansen, Jodi, and Kyle
The largest organ in the body, the skin, is required for diverse functions such as sensation, temperature regulation, and protection from environmental insults. My laboratory uses cellular and molecular biology techniques to investigate the role of a family of receptor tyrosine kinases in cutaneous biology and carcinogenesis. The erbB family of receptor tyrosine kinases consists of four members, three of which are expressed in the skin. Using genetically engineered mouse models lacking erbB receptor expression, we have shown that two of these receptors are critical for normal development of the skin and also contribute to skin carcinogenesis in response to environmental insults.
Loss of the erbB family member, the epidermal growth factor receptor (EGFR) results in defective proliferation, differentiation, and maintenance of cutaneous, gustatory and gut epithelia as well as altered patterning of cutaneous innervation. We have found that EGFR is an important regulator of interfollicular but not follicular proliferation, and of hair follicle but not interfollicular epithelial differentiation. EGFR is also critical for maintaining the integrity of the hair follicles during hair cycling. Signal transduction through members of the erbB family, including EGFR, influences glial and neuronal proliferation, differentiation, fate acquisition, neurite outgrowth, and survival. Signal transduction through erbB family members EGFR and erbB2, is vital for normal development of both motor and sensory neurons and for formation of the neuromuscular junction.
erbB receptors influence skin carcinogenesis in response to environmental insults. Skin cancer accounts for more than half of all cancer in the United States, with more than one million new cases of non-melanoma skin cancer per year. The primary cause of skin cancer is exposure to ultraviolet radiation in the form of sunlight. The specific mechanisms for UV-induced skin cancer development are not fully understood, although evidence suggests a significant role for the erbB receptors. These receptors are activated by UV and have been shown to suppress the normal cell-death response of cells exposed to UV. In addition, clinical studies have found elevated levels of erbB receptors in many skin cancers. Our research is investigating the hypothesis that erbB receptors increase skin carcinogenesis in response to UV. Since reagents that block erbB receptor signaling are currently in use in clinical trials for the treatment of non-skin cancers, this research could be readily translated into clinical trials for the prevention or treatment of human skin cancer.