Laurel A. Raftery


Department of Dermatology, Department of Cell Biology
Massachusetts General Hospital East
Cutaneous Biology Research Center CNY3
149 13th Street
Charlestown, MA 02129
Tel: (617) 726-1825
Fax: (617) 726-4453
Email: laurel.raftery@cbrc2.mgh.harvard.edu
3 postdoctoral fellows, 1 technician


In living tissues, self-renewal involves a balance between growth and differentiation that is coordinated within groups of cells through multiple cell-cell communication pathways. Responses to these pathways must be integrated, so that independent decisions made by single cells will result in functional tissue architecture. Our focus has been the mechanisms for responses to the transforming growth factorb (TGFb) family, a set of related soluble growth factors that direct organogenesis and homeostasis in organisms ranging from hydra to humans. To define the critical signaling systems that balance proliferation and differentiation in self-renewing epithelia, we use the fly ovary and mouse epidermis as our primary models. A recent focus has been on mechanisms for antagonism and synergy between BMP and EGF signals in vivo.

 

Initial transcriptional responses to TGFb signals are critical, both in normal tissue homeostasis and in the progression of carcinogenesis. The major TGFb family signal transducers are a set of transcription factors called Smad proteins. Studies of mammalian cultured cells have led to numerous models for modulation of Smad activity, both through feedback regulation and through cross-talk with other signaling pathways. We are using developmental genetics in Drosophila to understand the contributions of cross-regulatory mechanisms both to individual cells’ responses and to feedback regulation of signal levels for tissue maintenance and morphogenesis in vivo.

 

Many critical TGFb family functions, such as regulation of proliferation and differentiation, are mediated by target genes that express transcriptional regulators. We are studying a poorly understood class of target genes in the TSC-22/DIP/BUN family of transcriptional regulators (TDB proteins). In both flies and mice, TDB proteins appear to regulate the balance between growth and differentiation. We are using a self-renewing adult epithelium in the Drosophila ovary to place the function of TDB proteins within the genetic pathways for signaling responses. We are using the mouse epidermis as an in vivo system to translate our results to mammalian tissue homeostasis.

 

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BBS webpage updated 12/02/2009