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Exploring asymmetric cell division and cell fate

Our lab is interested in understanding the molecular mechanisms that control cell fate decisions following asymmetric cell division. Asymmetric cell division is a common strategy to achieve different cell fates during development, and dysregulation of asymmetric cell division in stem and progenitor cells likely contributes to a variety of human diseases, including cancer. In the fruit fly, Drosophila, neural stem and progenitor cells divide asymmetrically and segregate a cell fate determinant, Numb, to one daughter cell during mitosis. Numb protein functions as an inhibitor of the Notch signaling pathway. We currently use a combination of genetic, biochemical, molecular modeling, and live cell imaging approaches to study how cell fate determinants such as Numb are polarized during mitosis, and how, following asymmetric cell division, Notch signaling is activated in one daughter cell, and inhibited in the other daughter cell. Our studies have shown that a tumor suppressor gene lethal giant larvae and a novel transmembrane protein, Sanpodo, are critical for the correct cell fate assignments in the adult peripheral nervous system in flies. As many of the genetic programs used by organisms are evolutionarily conserved, understanding how the genes we've identified establish a context to control Notch signaling in asymmetrically dividing cells will help guide future studies addressing mechanisms of stem and progenitor cell regulation in development and disease.

Epigenetics and Progenitor Cell Keystone program