Robert C. Smart

Goodnight Distinguished Chair in Molecular Toxicology
Director, Center for Human Health and the Environment

Research Interests of the Cell Signaling and Cancer Group

Cancer susceptibility is determined by complex interactions between age, environment and an individual’s genetic make-up.  Our research involves the identification and characterization of genes/signaling pathways that are determinants of susceptibility to cancer, particularly as it relates to gene-environment interactions.  My laboratory was first to report roles for CCAAT/enhancer binding protein transcription factors (C/EBPs) in epithelial skin cancer, the DNA damage response, apoptosis and squamous differentiation.  Current research projects include: i) the role of C/EBPs in the regulation of proliferation, differentiation, apoptosis and cancer, ii) the role of C/EBPs in the DNA damage response network/cell cycle checkpoints, iii) the signaling pathways involving oncogenes including Ras and receptor tyrosine kinases that control the transcription activity of C/EBPs; iv) C/EBPb and the tumor cytokine microenvironment in cancer development v) and use of genetically modified mice to characterize the function of genes in cellular processes involving cell cycle regulation, differentiation, apoptosis, DNA damage response and cancer pathogenesis. Our research is focused on skin, esophageal and pancreatic cancer.

I serve as Director of Graduate Programs for the Department of Environmental and Molecular Toxicology.  I also serve as the Director of the NIEHS Training Program in Molecular Pathways to Pathogenesis in Toxicology and the Director of the Center for Human Health and the Environment (CHHE).  CHHE brings together 39 investigators across our campus to form an interdisciplinary team to conduct research aimed at the understanding and prevention of the adverse impacts of environmental factors on human health (   I am the co-editor of a textbook, Molecular and Biochemical Toxicology 4th edition, utilized in toxicology programs worldwide.

 Research Areas:  CCAAT/enhancer binding proteins, cancer biology, gene-environment interactions in cancer susceptibility, DNA damage response

Selected Publications

Gaddameedhi, S., C.P. Selby, W.K. Kaufmann, R.C. Smart and A. Sencar. Control of skin cancer by the circadian rhythm. Proc. Natl. Acad. Sci. USA 108:18790-18794 2011

Ming, M., L. Feng, C.R. Shea, K. Soltani, B. Zhao, W. Han, R.C. Smart, C.S. Trempus and Y.Y. He.  PTEN positively regulates UVB-induced DNA damage repair. Cancer Res 71:5287-5295 2011

Thompson, E.A., S. Zhu, J.R. Hall, J.S. House, R. Ranjan, J.A. Burr, Y-Y. He, D.M. Owens and R.C. Smart. C/EBPa expression is downregulated in human nonmelanoma skin cancers and inactivation of C/EBPa confers susceptibility to UVB-induced skin squamous cell carcinomas. J. Invest. Dermatol. 131:1339-1346 2011

Kim, T.H., S.L. Chiera, K.E. Linder, C.S. Trempus, R.C. Smart and J.M. Horowitz. Overexpression of transcription factor Sp2 inhibits epidermal differentiation and increases susceptibility to wound- and carcinogen-induced tumorigenesis.  Cancer Res 70:8507-8516 2010

Omori, E., K. Matsumoto, S. Zhu, R.C. Smart and J. Ninomiya-Tsuji. Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells. Cancer Res 70:8417-8425 2010

Lee, S., J.D. Shuman,  T. Guszczynski, K. Sakchaisri, T. Sebastian, T.D. Copeland, M. Miller, M.S. Cohen, R.C. Smart, Z. Xiao, L.R. Lu, T.D. Veenstra and P.F. Johnson.  RSK-mediated phophorylation in the C/EBPb leucine zipper regulates DNA binding, dimerizations and growth arrest. Mol. Cell Bio. 11:2621-2635 2010

House, J.S., S. Zhu, R. Ranjan, K. Linder and R.C. Smart C/EBPa and C/EBPb are required for sebocyte differentiation and stratified squamous differentiation in adult mouse skin PloS ONE 5;9837 2010

Ranjan, R., E. A. Thompson, K. Yoon, R. C. Smart. C/EBPα expression is partially regulated by C/EBPβ in response to DNA damage and C/EBPα-deficient fibroblasts display an impaired G1 checkpoint. Oncogene 28: 3235-45 2009

Ewing, S. J., S. Zhu, F. Zhu, J. S. House and R. C. Smart. C/EBPβ represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19Arf. Cell Death and Diff 15 : 1734-1744 2008

Yoon, K., S. Zhu, S. J. Ewing and R. C. Smart. Decreased survival of C/EBPβ -deficient keratinocytes is due to aberrant regulation of p53 levels and function. Oncogene 26 : 360-367. 2007.

Loomis, K. D., S. Zhu, K. Yoon, P. F. Johnson and ,R. C. Smart .Genetic ablation of C/EBPα in epidermis reveals its role in suppression of epithelial tumorigenesis. Cancer Res 67 : 6768-76 2007

Omori, E., K. Matsumoto, H. Sanjo, S. Sato, S. Akira, R. C. Smart, and J. Ninomiya-Tsuji TAK1 is a master regulator of epidermal homeostasis involving skin inflammation and apoptosis J. Biol. Chem. 281 : 19610-19617. 2006.

Sterneck, E., S. Zhu, A. Ramierz, J. L. Jorcano and R. C. Smart. Conditional ablation of C/EBPβ demonstrates its keratinocyte specific requirement for cell survival and mouse skin tumorigenesis. Oncogene 25 :1272-1276. 2006.

Shim, M., K. L. Powers, S. J. Fry, S. Zhu and R. C. Smart .Diminished expression of C/EBPα in skin carcinomas is linked to oncogenic Ras and re-expression of C/EBPα in carcinoma cells inhibits proliferation. Cancer Res, 65 : 861-867. 2005

Shuman, J. D., T. Sebastian, P. Kaldis, T. D. Copeland, S. Zhu, R.C. Smart and P. J. Johnson. Cell cycle-dependent phosphorylation of C/EBPβ mediates oncogenic cooperativity between C/EBPβ and H-RasV12. Mol. Cell. Bio. 24 : 7380-7391. 2004

Yoon, K. and R. C. Smart. CCAAT/enhancer binding protein-alpha is a DNA-damage inducible p53-regulated mediator of the G1 checkpoint. Mol. Cell. Bio. 24 : 10650-10660. 2004