Research

Our laboratory studies the mechanisms that regulate growth at the level of individual cells as well as the entire organism.

We primarily study the mechanisms that function during the development of an organism to determine its eventual size and form. We conduct genetic studies in the fruitfly, Drosophila melanogaster, to identify genes that regulate growth, cell proliferation and cell death. Our studies have also helped identify genes that are mutated in some cancers.

Our Screen

Over the last five years, we have conducted a genetic screen that has led to the identification of many genes that restrict tissue growth and cell proliferation in vivo. Following mutagenesis, we generated flies with eyes that contain both wild-type tissue (marked red) and mutant tissue (marked white). By comparing the relative representation of the two types of tissue we can identify mutations that allow mutant cells to outgrow their wild type neighbors.

The mutant eye (right image) shows an increase in the relative representation of mutant tissue (white) when compared to the control (left image).

Once we identify the mutant flies, we map the mutation and characterize the mutated gene at the molecular level. Further studies of the encoded protein usually provide clues as to how this gene functions to regulate tissue growth. Our eventual aim is to understand the cellular circuitry that regulates the growth process.

Genes we have studied

Genes identified in our screen include the orthologs of the genes mutated in the human disease tuberous sclerosis (Tsc1 and Tsc2), pten, components of the RTK/Ras pathway (e.g. Gap1, argos) as well as many genes that function to regulate growth in ways that are not well understood. One of the genes that we have characterized archipelago, encodes a protein that facilitates the destruction of Cyclin E and Myc. Another set of three genes (salvador, warts and hippo) constitute a novel pathway that restricts tissue growth.

For the human orthologs of archipelago and salvador, we identified mutations in cancer cell lines. We and others have identified mutations in the human ortholg of archipelago (hCdc4, FBW7) in primary human tumors.