Bogi Andersen
M.D., University of Iceland, 1981
Department of Medicine
University of California, Irvine
Sprague Hall, Room 206
Irvine, CA 92697-4030
(949) 824-9093, 9372
bogi@uci.edu
Research Interests:
Transcriptional regulation in normal and diseased epithelia
The long-term goal of the Andersen laboratory is to understand transcriptional control mechanisms that underlie normal development of epidermis, hair follicles and mammary glands, and to use this knowledge to gain insights into carcinogenesis in epithelial tissues. To reach this goal, the laboratory uses a variety of approaches. These include cDNA cloning methods to identify candidate regulators, mouse genetics to test the function of candidate genes and in vitro studies to understand transcriptional mechanisms.
Currently, research in the Andersen laboratory focuses on the role of two classes of transcriptional regulators: POU homeodomain factors and LIM domain factors. Epidermally expressed POU homeodomain proteins seem to play a role in repressing expression of the keratin 5 and 14 genes, which are normally expressed in undifferentiated keratinocytes but silenced in differentiated cells. Our studies suggest that POU domain factors may interfere with the function of CBP/p300 co-regulators at the core promoter of the keratin 14 gene.
A major focus of the Andersen laboratory involves investigating the roles of Clim/Nli/Ldb co-activators in stratified epithelia and mammary glands. The Clim proteins were discovered based on their ability to bind to LIM domains of LIM homeodomain factors and confer transcriptional activation by this class of DNA-binding proteins. One member of this family of co-activators, Clim-2, is highly expressed in epithelial cells of the epidermis and internal epithelial linings. We have found that Clims interacts with the LIM only protein, LMO-4, which is expressed in an overlapping manner in epithelial tissues. Using genetic mouse models we have data indicating that this transcriptional complex may be an important regulator of epithelial morphogenesis and homeostasis, including that of the hair follicle morphogenesis and cycling. Presently, we are investigating how the LMO/Clim transcriptional complex relates to known signaling pathways involved in epithelial regulation, and how it interacts with DNA-binding proteins.
Accumulating evidence suggest that the hair follicle plays important roles in skin carcinogenesis. Some epidermal cancers, especially basal cell carcinoma, may originate from hair follicle cells. In addition, subversion of normal regulators of hair morphogenesis, such as the Wnt and hedgehog pathways, is responsible for skin cancer. We are therefore interested in investigating whether abnormalities in the Clim/LMO transcriptional complex may play a role in epithelial carcinogenesis in epidermis and mammary glands.
Selected Publications:
Andersen, B., Hariri, A., Pittelkow, M.R., & Rosenfeld, M.G. 1997. Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus gene expression. J. Biol. Chem. 272:15905-15913.
Bach, I., Carriere, C., Ostendorff, H.P., Andersen, B., & Rosenfeld, M.G. 1997. A family of LIM domain associated cofactors confer transcriptional synergism between LIM- and Otx homeodomain proteins. Genes & Dev. 11:1370-1380.
Andersen, B., Weinberg, W.C., Rennekampff, O., McEvilly, R., Bermingham, J.R., Hooshmand, F., Vasilyev, V., Hansbrough, J.F., Pittelkow, M.R., Yuspa, S.H., & Rosenfeld, M.G. 1997. Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation. Genes & Dev. 11:1873-1885.
Sugihara, T.M., Bach, I., Kioussi, C., Rosenfeld, M.G. & Andersen, B. 1998. Mouse Deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators. Proc. Natl. Acad. Sci. 95:15418-15423.
Bach, I., Rodriguez-Esteban, C., Carriere, C., Bhushan, A., Krones, A., Rose, D.W., Glass, C.K., Andersen, B., Belmonte, J.C.I. & Rosenfeld, M.G. 1999. RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nature Genetics 22:394-399.
Suzuki, K., Yamanishi, K., Mori, O., Kamikawa, M., Andersen, B., Kato, S., Toyoda, T., & Yamada, G. 2000. Defective terminal differentiation and hypoplasia of the epidermis in mice lacking the Fgf10 gene. FEBS Lett. 8:53-56.
Sugihara, T.M., Kudryavtseva, E., Kumar, V., Horridge, J.J. & Andersen, B. 2001. The POU domain factor Skin-1a represses the keratin 14 promoter independentof DNA binding: possible role for interactions between Skn-1a and CBP/p300. J. Biol.Chem. 276:33036-33044.
Kudryavtseva, E., Sugihara, T.M., Wang, N., Lasso, R., Gudnason, J.F., Lipkin, S.M. & Anderson, B. 2003. Identification and characterization of a novel LMO-4-interacting protein, mammalian Grainyhead-like Epithelial Transactivator (GET-1). Dev Dynamics 226:604-17.
Wang, N., Kudryavtseva, E. Ch'en, I.L., McCormick, J., Sugihara, T.M., Ruiz, R. & Anderson, B. 2004. Expression of an engrailed-LM04 fusion protein in mammary epithelial cells inhibits mammary gland development in mice. Oncogene. In press.
