OREGON STATE UNIVERSITY
Open search box
Investigating signaling and transcriptional networks that regulate skin development with cellular, molecular, and genetic techniques. We discovered a transcriptional factor, CTIP2, which is expressed in both the hair follicle and basal skin cells and plays an important role in regulation. Some key functionalities of CTIP2 include control of epidermal proliferation, switching from proliferation to differentiation in the epidermis, and terminal differentiation of epidermal cells.
We are collaborating with Mark Leid at OSU to study the signaling pathways and transcriptional networks that regulate the development of mature skin.
UV radiation is a key risk factor for the development of both melanoma and non-melanoma skin cancers, and we are investigating how cell signaling plays a role in that process. The focus is on how skin cells communicate with each other in disease and healthy states with a focus on nuclear hormone receptors such as retinoid-x-receptors.
In addition to these investigations, we have also developed a spatiotemporally-controlled somatic mutagenesis technique based on the bacteriophage P1-Cre/lox strategy to avoid problems common to traditional gene targeting and pleiotrophic gene effects. We have examined the role these receptors play in skin ontogenesis, adult skin homeostasis, stress responses, various skin diseases, and melanoma and non-melanoma skin cancers.
These projects have been conducted in collaboration with Zalfa Abdel-Malek from the University of Cincinnati, Pierre Chambon and Daniel Metzger of IGBMC, France, and Lionel Larue from the Institut Curie, France.
Currently, the mechanisms involved in establishing the epidermal permeability barrier are poorly understood but mutations of genes linked with skin barrier functions have been observed to cause impairment of barrier function, increased susceptibility to inflammatory skin diseases, and neonatal death in severe cases. Our research in this area is focused on using novel animal models to improve the understanding of these malfunctions, especially in relation to lipid composition. We use mass spectroscopy-based lipidomics techniques to observe the change of lipid levels followed by a reverse genetics examination to investigate molecular mechanisms at work.
This project operates in collaboration with Fred Stevens at OSU as well as Eric Simpson and John Hanifin at OHSU.
Nuclear receptors of interest, including retinoid-x-receptors, retinoic acid receptors, vitamin-D-receptors, peroxisome-proliferator-activated receptors, and liver-x-receptors, are being examined for their role in melanoma tumors. One of our studies has illustrated that keratinocytic RXRa, when combined with activated CDK4, leads to development of invasive melanomas in mouse models. We investigated the role of nuclear hormones in both the progression of melanoma and conversion of malignant cells in tumors.
Another area of this project has been examining the relationship between these nuclear receptors and the Ras-Raf or Pten-Akt signaling pathways.
Collaborators on this project include Pierre Chambon and Daniel Metzger from IGBMC in France, L. Larue of the Pasteur Institute in France, and Friedrich Beermann from ISREC in Switzerland.