Yu-Ying He, Ph.D.

Genetic and Environmental Determinants of Genomic Stability in Skin Cells

Research Summary

Our laboratory is interested in understanding the molecular mechanisms in UV-induced skin carcinogenesis to identify key molecular pathways that can facilitate the development of effective preventive and therapeutic strategies. Skin cancer is the most common type of cancer in the United States (US), and its incidence continues to rise each year. The major risk factor is environmental ultraviolet radiation from sunlight or UV-emitting tanning beds. Both UVB (280-315 nm) and UVA (315-400 nm) plays important roles in skin carcinogenesis. Our understanding of skin cancer is far from complete.

Our laboratory is engaged in detecting the biological regulation of key molecular/cellular processes that determine susceptibility to skin carcinogenesis. These processes include DNA damage repair, cell cycle checkpoints, and apoptosis. UV damages DNA to form two major DNA damage products, cyclobutane pyrimidine dimer (CPD) and pyrimidine (6-4) pyrimidone photoproduct (6-4PP). Unrepaired DNA damage causes somatic mutations, and thus tumorigenic transformation. Cells are equipped with complex DNA repair and response mechanisms to maintain their genome. In response to UV radiation, cells attempt to repair the damage, through the process of nucleotide excision repair (NER). This repair system utilizes sophisticated machinery to eliminate UV-induced DNA damage. Meanwhile checkpoint signaling is activated, which arrests the cell cycle and gives the cell time to repair the damage before continuing to divide. Excessive damage to a cell leaves it with two potential pathways: undergo apoptosis and die, or survive at the cost of living with a modified genome. Impairing these crucial molecular and cellular processes increases individual susceptibility to skin cancer.

We use molecular, genetic, and translational approaches in cell culture models and clinically relevant animal models to investigate how DNA repair and DNA damage responses of skin cells are regulated in vivo and what their impact is on skin carcinogenesis. Currently our research focuses on the regulation and function of the tumor suppressor PTEN and the deacetylase SIRT1 in skin carcinogenesis, and the molecular basis for increased skin tumorigenesis in organ transplant recipients. Our long-term goal will be to identify previously unrecognized regulatory processes that predict susceptibility to skin carcinogenesis, and thus to improve our ability to prevent and treat skin cancer.

Selected Papers

Ming M, Shea CR, Guo XM, Li XL, Soltani K, Han WN, He YY. Regulation of Global Genome Nucleotide Excision Repair by SIRT1 through xeroderma pigmentosum C. Proc. Natl. Acad. Sci. USA, 107 (2010) 22623-22628.

Ming M, Han WN, Maddox J, Soltani K, Shea CR, Freeman D, He YY. UVB induced ERK/AKT-dependent PTEN suppression promotes survival of epidermal keratinocytes. Oncogene, 29 (2010) 492-502.

Han WN, Ming M, He TC, He YY. Immunosuppressive Cyclosporin A Activates AKT in Keratinocytes through PTEN Suppression: IMPLICATIONS IN SKIN CARCINOGENESIS.  J. Biol. Chem., 285 (2010) 11369-11377.

Thompson EA, Zhu SY, Hall JR, House, JS, Ranjan R, Burr J, He YY, Owens  expression is ablated in human nonmelanoma skin cancersaDM, and Smart RC. C/EBP  confers susceptibility to UVB-induced skin squamousaand inactivation of C/EBP cell carcinomas. J. Invest. Dermatol., 131 (2011) 1339-1346.

Ming M, Shea CR, Feng L, Soltani K, He YY. UVA induces lesions resembling seborrheic keratoses development in mice with keratinocyte-specific PTEN down-regulation. J. Invest. Dermatol., 131 (2011) 1583-1586.

Han WN, Ming M, He YY. Caffeine promotes ultraviolet B-induced apoptosis in human keratinocytes without complete DNA repair.  J. Biol. Chem., 286 (2011) 22825-22832.

Ming M, Feng L, Shea CR, Soltani K, Zhao B, Han WN, Smart RC, Trempus CS, He YY. PTEN positively regulates UVB-induced DNA damage repair. Cancer Res., 71 (2011) 5287-5295.