Research & Publications
Sean Christensen, MD, PhD, is an Assistant Professor of Dermatology whose research is focused on the elucidation of cellular and molecular mechanisms of skin cancer development and the application of this knowledge to clinical patient care. It is well established that ultraviolet radiation is the primary driver of skin cancer pathogenesis, but the cellular and genetic events that drive the expansion and progression of malignant precursors in the skin remain poorly understood. An unexplored aspect of gene expression in the epidermis is post-transcriptional regulation by RNA binding proteins. By reducing mRNA stability and translation efficiency, RNA-binding proteins, such as Pumilio 1 and 2, can coordinately regulate the expression of large sets of functionally related genes and maintain genomic stability in response to DNA injury. In collaboration with Dr. Haifan Lin, who originally defined the role of Pumilio proteins in stem cell function, Dr. Christensen has identified a role for Pumilio proteins in regulating the response of epidermal keratinocytes to ultraviolet radiation. Two major goals of Dr. Christensen’s laboratory research are to define the mechanism by which Pumilio proteins promote genomic stability and to define the consequences of impaired Pumilio function on ultraviolet-induced mutation, clonal expansion and cancer development.
Dr. Christensen also leads clinical and translational research projects focused on skin cancer prevention and treatment. Working with the Genomics and Bioinformatics Core at the Yale Stem Cell Center, Dr. Christensen has developed a method to identify rare somatic mutations in human skin adjacent to surgically excised skin cancers. Using next generation sequencing technology, this method will investigate the relationship between these ultraviolet-induced somatic mutations and skin cancer risk. In addition to identifying critical mutations for skin cancer pathogenesis, this research could more precisely identify patients for targeted interventions to prevent skin cancer development. Dr. Christensen is also conducting clinical research on surgical and non-surgical treatment of skin cancer, cancer prevention strategies for patients with multiple skin cancers, and management of high risk squamous cell carcinoma and other rare skin cancers, and he serves as principal investigator in a phase III clinical trial of a novel topical treatment for basal cell carcinoma.
Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Skin Neoplasms; Ultraviolet Rays; Keratosis, Actinic
- Cancer of the SkinChristensen, S.R., and Leffell, D.J. in Cancer: Principles and Practice of Oncology, 10th Edition, Lippincott Williams &Wilkins.