UM Duluth
Duluth
The molecular mechanisms that mediate the influence of environmental toxins on development and human health remain to be fully understood. Toward this goal, this lab aims to elucidate novel developmental functions of the classic Keap1-Nrf2 detoxifying pathway in Drosophila (fruit fly). While the mechanisms whereby Keap1-Nrf2 activates detoxifying genes in response to internal and external toxins are well understood, how Keap1 and Nrf2 regulate developmental genes and programs is unclear. Previous studies suggested that Drosophila Keap1-Nrf2 proteins (dKeap1-CncC) can bind to chromatin and likely switch on/off developmental genes by altering DNA packaging to an opened/condensed status (referred to as an "epigenetic" mechanism). This project will fully explore the molecular and biological functions of dKeap1/CncC by identifying protein partners that cooperate with dKeap1/CncC in nuclear organization and chromatin architecture, determining how dKeap1 controls higher-order chromatin structure in response to toxins, and screening for developmental genes/programs that are directly controlled by dKeap1. The researchers expect that these studies will reveal a novel molecular bridge that mediates epigenetic and developmental adaptations to environmental toxins. This research will contribute to a better understanding of the complicated roles of Keap1 and Nrf2 in human diseases, such as cancer.