Ahmed, Y., Hayashi, S., Levine, A., and Wieschaus, E. (1998). Regulation of Armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development. Cell 93, 1171-1182.
Ahmed, Y., Nouri, A., and Wieschaus, E. (2002) Drosophila Apc1 and Apc2 regulate wingless transduction throughout development. Development 129, 1751-1762.
Research / Lab Interests
GENES INVOLVED IN THE REGULATION IF PROGRAMMED CELL DEATH IN ANIMALS:
Our goal is to understand how the balance between cell proliferation, differentiation and apoptosis is regulated, as this process is critical not only for normal development, but also in the prevention of tumorigenesis. We study the adenomatous polyposis coli (APC) tumor suppressor, inactivation of which triggers the development of the vast majority of colon carcinomas. APC negatively regulates b -catenin, a protein that functions both in epithelial cell adhesion, and as a transcriptional transactivator when complexed with the DNA binding protein T-cell factor (Tcf). We have chosen Drosophila to study the regulation of b -catenin by APC because the signaling components in the APC/b-catenin pathway are well conserved from flies to humans, the roles of the Drosophila homolog of b -catenin in both cell adhesion and transcriptional activation are well documented, and powerful genetics are available.
Our work has revealed that b-catenin is among the signaling molecules that can induce either cell proliferation, cell differentiation or apoptotic death, its effects likely dependent on the state of cellular differentiation. Thus distinct downstream effectors that control the decision between proliferation, differentiation and death must function in response to b-catenin. Presently we are identifying downstream effectors in the APC/b-catenin pathway using Drosophila genetics, as they are crucial for understanding the imbalances in proliferation and apoptosis that underlie carcinogenesis, and may serve as molecular targets for intervention. Our analysis of the biochemical and cell biological properties of these molecules will be conducted in the context of answering the following questions: How do cells decide to activate either proliferation, differentiation, or apoptosis in response to the same signal? How does the differentiation state of the cell determine this choice?
