Funktion von RhoA in der Hautentwicklung und Hyperproliferation

• Applicant: Dr. Simone Grethe
• Subject Area: Pathology
• Term: Funded in 2006
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 30965388

RhoA is a small GTPase regulating cell attachment, cell contraction, cell division and several other cellular processes. In humans, RhoA is often overexpressed in tumors. The function of RhoA has mainly been studied in vitro using inhibitors, which also reduce the activity of the related proteins RhoB and RhoC. All three proteins, RhoA, B and C, are ubiquitously expressed. Nothing is known about the specific function of RhoA in vivo. The group of Professor Cord Brakebusch has already generated mice with a conditional knockout of RhoA restricted to keratinocytes. These mutant mice will be studied with respect to keratinocyte differentiation in epidermis and hair follicles, cell-cell contacts, extracellular matrix deposition, and wound healing. To reveal the mechanisms causing the phenotypes, primary and spontanously immortalised keratinocytes will be investigated in vitro using inhibitors, activators and, in case of immortalised keratinocytes, by lentiviral transfections of dominant negative or constitutively active mutant proteins. In wound closure assays I will assess directed cell migration and wounding induced signaling. This study will elucidate specific functions of RhoA in vivo, focussing on skin development, skin maintenance and wound healing.

• DFG Programme: Research Fellowships
• International Connection: Denmark
• Host: Professor Dr. Cord Brakebusch