Research:

Our goal is to understand the genetic regulation of insulin-producing cell (IPC) specification.  We have shown that the brain IPCs of Drosophila are homologous in function to pancreatic islet ß-cells, and are using their development as a model system. Directed programming of IPCs from uncommitted progenitors is a prevailing goal of diabetes research that is expected to lead to cell-based therapies for patients with either type 1 or 2 diabetes. Our emerging data indicate that features of IPC development in Drosophila are relevant to the development of human IPCs and placodal development of endocrine cells in general.

We have produced a detailed lineage map for the brain IPCs and can follow cell fate in this developing lineage at all stages with combinations of molecular markers. We have identified a near complete inventory of transcription factors specifically expressed in the developing lineage. This set of factors, together with other genetic analysis of cell signaling pathways, has led us to hypothesize that cell specification of IPCs comprises at least three major steps governed by gene regulatory networks: 1) establishment of a stable gene regulatory state throughout the endocrine compartment, beginning with the onset of zygotic gene expression; 2) establishment of an 8-cell neuroectodermal placode harboring a combinatorial code for IPC lineage progenitor identity; and 3) intra-placodal cell-cell interaction that acts on a small set of transcription factors to single out an IPC progenitor from a group of developmentally equivalent cells. Our current research focus is testing aspects of this model and examining pattern formation in the endocrine system in general.

Selected Publications:

Rulifson, E. 2008. Fly-let Biology and the High Protein/Low Carb Diet. Cell Metabolism. 7(4):281-3. download paper

Wang, S., Tulina, N., Carlin, D.L. and Rulifson, E.R. 2007. The Origin of Islet-like Cells in Drosophila Identifies Parallels to the Vertebrate Endocrine Axis. PNAS 104:19873-19878. download paper

Kim, S. K. and Rulifson, E. J. (2004). Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature 431 , 316-20. download paper

Rulifson, E. J., Kim, S. K. and Nusse, R. (2002). Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296 , 1118-20. download paper