Bogi Andersen
Biological Chemistry, School of Medicine
Phone: (949) 824-9093
Email: bogi@uci.edu
www.ucihs.uci.edu/biochem/faculty/Andersen.html
Laboratory Home Page
http://www.faculty.uci.edu/profile.cfm?faculty_id=4704
Bogi Andersen
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. Currently, research focuses on the role of two classes of transcriptional regulators: LIM domain factors and Grainyhead transcription factors.
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, Clim2, is highly expressed in epithelial cells of the epidermis and internal epithelial linings. They have found that Clims interacts with the LIM only protein, LMO4, which is expressed in an overlapping manner in epithelial tissues. Using genetic mouse models they 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, they 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.
In addition, they have found that the LMO4 gene plays important roles in lobuloalveolar development of the mammary gland. Mice with mammary gland-specific deletion of the LMO4 gene show delayed mammary gland development due to decreased mammary epithelial cell proliferation. This is consistent with common upregulation of LMO4 in human breast cancer. Molecular studies suggest that LMO4 can modulate activity of the TGFbeta/BMP pathways.
Another major focus of Dr. Andersen’s laboratory has been elucidating the role of Grainyhead-like transcription factor Get1/Grhl3. They have discovered that this factor promotes differentiation of epidermal keratinocytes and also promotes keratinocytes migration. They are now investigating whether Get1 affects migration of skin cancer cells.
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. Dr. Andersen is therefore interested in investigating whether abnormalities in the Clim/LMO transcriptional complex may play a role in epithelial carcinogenesis in epidermis.
Selected Publications:
Yu, Z., Lin, K. K., Bhandari, A., Spencer, J. A., Xu, X., Wang, N., Lu, Z., Gill, G. N., Roop, D. R., Wertz, P., and Andersen, B. (2006). The Grainyhead-like epithelial transactivator Get-1/Grhl3 regulates epidermal terminal differentiation and interacts functionally with LMO4. Dev Biol 299(1), 122-36.
Lu, Z., Lam, K. S., Wang, N., Xu, X., Cortes, M., and Andersen, B. (2006). LMO4 can interact with Smad proteins and modulate transforming growth factor-b signaling in epithelial cells. Oncogene 25(20), 2920-2930.
Wang, N., Lin, K. K., Lu, Z., Lam, K. S., Newton, R., Xu, X., Yu, Z., Gill, G. N., and Andersen, B. (2007). The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells. Oncogene 26(44), 6431-41.
Xu, X., Mannik, J., Kudryavtseva, E., Lin, K. K., Flanagan, L. A., Spencer, J., Soto, A., Wang, N., Lu, Z., Yu, Z., Monuki, E. S., and Andersen, B. (2007). Co-factors of LIM domains (Clims/Ldb/Nli) regulate corneal homeostasis and maintenance of hair follicle stem cells. Dev Biol 312(2), 484-500.
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