Pilot Project

Project Title:  Function of Hairless in UV-induced Skin Cancer Susceptibility

Principal Investigator:  Liang Liu, PhD, Associate Research Scientist, Dept. of Dermatology

Co-Investigator:  Angela Christiano, PhD, Professor in the Dept. of Dermatology

Year: 2011   

Award Amount:  $25,000

Abstract:  Non-melanoma skin cancer (NMSC), including squamous cell (SCC) and basal cell (BCC) cancers, is the most prevalent type of human cancer. A well-known, common cause of skin cancer is excessive exposure to UV irradiation from sunlight that can cause DNA damage, inflammation, skin aging, and eventually skin cancer. Multiple signaling pathways and transcription factors have been investigated to understand the connection between sun exposure and skin cancer, however, the exact mechanisms underlying UV action in promoting skin cancer development await further exploration. Another priority in skin cancer research is to identify novel molecular targets for chemoprevention and therapy of skin cancer.  The hairless gene is a key regulator of the balance between cell proliferation and differentiation in the skin. Mutations in hairless cause permanent hair loss in both humans and rodents. Mice that harbor functional mutations in hairless are extremely susceptible to developing skin cancer in response to UV irradiation. Microarray analysis of hairless-mutant versus wild-type mouse skin identified genes that are regulated by hairless including cell cycle regulation and apoptosis genes, and in particular, numerous genes that are known targets of NFκB signaling. These novel findings, together with our previous observations of dysregulated apoptosis in the hair matrix of hairless mutant mice, strongly suggest that loss of hairless function in the skin may play a causal role in skin photocarcinogenesis.

In this proposal, we will test the hypothesis that hairless is a key regulator of the balance between cell proliferation and differentiation via its novel role as an epigenetic regulator of target gene activity. We will attempt to address the following three essential questions: 1) how does hairless function in the skin; 2) does hairless control cancer growth via regulating the activities of other genes; 3) can we reduce UV-induced skin cancer incidence by restoring or enhancing hairless function in skin cells?