Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Skin Neoplasms; Ultraviolet Rays; Keratosis, Actinic
Stem Cell Center, Yale: Stem Cell Self-Renewal and Cell Symmetry
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 Dr. Lin and 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 investigating photodynamic therapy for as a treatment for superficial squamous cell carcinoma, and retrospective studies to define clinical and pathologic features associated with adverse outcomes in advanced basal cell carcinoma, high risk squamous cell carcinoma and rare skin cancers.
- Bazex syndrome (acrokeratosis paraneoplastica). Poligone B, Christensen SR, Lazova R, Heald PW. Lancet. 2007 Feb 10;369(9560):530.
Histopathologic assessment of depth of follicular invasion of squamous cell carcinoma (SCC) in situ (SCCis): Implications for treatment approach.
Christensen SR, McNiff JM, Cool AJ, Aasi SZ, Hanlon AM, Leffell DJ. Journal of the American Academy of Dermatology, 2016 Feb;74(2):356-62.
- Sirolimus-associated rapid progression of leg ulcers in a renal transplant recipient Totonchy, MB, Colegio, OR, Christensen, SR. JAMA Dermatology, 2016; 153:105-106.
TLR9 promotes tolerance by restricting survival of anergic anti-DNA B cells, yet is also required for their activation.
Nickerson, K.M., Christensen, S.R., Cullen, J.L., Meng, W., Luning Prak, E.T., and Shlomchik, M.J. J. Immunol. 190:1447-1456.
- Erythroderma and spontaneous blistering in a 49 year-old man Trufant, J.W., Christensen, S.R., McNiff, J.M., and Choi, J.N. Archives of Dermatology, 146:1419-1424.
Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus
Christensen, S.R., Shupe, J., Nickerson, K., Kashgarian, M., Flavell, R.A., and Shlomchik, M.J. Immunity 25:417-428.
- Cancer of the Skin Christensen, S.R., and Leffell, D.J. in Cancer: Principles and Practice of Oncology, 10th Edition, Lippincott Williams &Wilkins.