Regulation of skin morphogenesis, wound healing and turmorgenesis by the Nrf2 transcription factor

• Applicant: Dr. Christina Siemes
• Subject Area: Dermatology
• Term: from 2005 to 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5455497

Injury of adult tissues initiates a series of biological events, which finally leads to at least partial reconstitution of the damaged regions. Because a series of conditions is associated with impaired healing, there is a strong need to develop strategies for the improvement of the repair process. In recent years a series of genes were identified, which are regulated by skin injury and which are therefore candidate regulators of the repair process. One of these genes encodes the transcription factor Nrf2, a potent inducer of various cytoprotective proteins. Therefore, it is of great interest to study the consequences of Nrf2 activation in keratinocytes in vitro and in vivo. For this purpose, I will express a fusion protein of a constitutively active Nrf2 mutant (caNrf2) and the hormone-binding domain of a mutant estrogen receptor in cultured keratinocytes. In addition, I will generate transgenic mice expressing caNrf2 in the basal layer of the epidermis in a tamoxifen-inducible manner. These experiments should provide further insight into the mechanisms of action of Nrf2 in normal, wounded and disease skin and provide the basis for the development of therapeutics for the improvement of wound repair and for the prevention of skin carcinogenesis.

• DFG Programme: Research Fellowships