Research at the Magnuson Lab

We are interested in learning how to manipulate the cell fate potentials in order to generate new pancreatic beta cells for treating diabetes. Over the past few years our efforts have been focused on developing the tools and strategies necessary to monitor and manipulate the expression of key transcription factors that are vital for formation of the pancreas. We are now utilizing these tools to both define and manipulate cell fate decisions that first dictate the formation of definitive endoderm, and then the pancreas.

As model systems we principally use mouse and human ES cells. By applying the methods of BAC recombineering, gene targeting and recombinase-mediated cassette exchange we have tagged several key genes that control cell fate decisions in early development with different colored fluorescent proteins. This enables us to easily visualize when and/or where these genes are expressed, both in mouse embryos and in cultured stem and progenitor cells. In addition, by using the reverse tetracycline transcriptional activator (rtTA) system we will be able to simultaneously force expression of transcription factors to cause either the reprogramming of differentiated cells into iPS cells, and to stimulate the trans-differentiation of one cell type to another. Finally, we are developing new databases to facilitate the analysis and sharing of our results.

Through the combined use of these new tools, strategies and informatics resources we anticipate being able to both explore and define processes in early development that have previously been beyond our reach. This information will, in turn, inform us how to direct the differentiation of pleuripotent stem/progenitor cells towards a pancreatic beta cell fate.