Dr. Bruce Edgar

Seminar Details

Host: Dr. Michael Polymenis

Time: 4:00pm-5:00pm

Location: BICH Rm 108

Seminar Abstract

Proliferative, multipotent stem cells are critical for development, tissue maintenance, reproduction, and longevity, and stem cell dysfunctions underlie common maladies ranging from degenerative diseases to chronic inflammation to the majority of cancers. Understanding the regulation of stem cell growth, proliferation, and differentiation is, therefore, essential to develop strategies to combat such diseases. In this talk I will present results from our genetic analysis of intestinal stem cell (ISC) regulation during regeneration in the midgut of the fruit fly, Drosophila melanogaster. As in humans, the fly’s gut epithelium is constantly renewed by dividing ISCs, which replace cells lost to digestive wear and tear and insults like infections, which hyper-activate ISC growth and division. I will discuss how differentiated ISC progeny – the enterocytes – sense epithelial damage and communicate to ISCs through pro-proliferative JAK/STAT and EGFR/ERK signaling to maintain gut homeostasis. I will detail our recent discovery that damage-dependent oxidative stress in enterocytes causes translation defects that activate the ancient, conserved GCN2/p-eIF2α stress response system to induce the transcription factor Xrp1, a homolog of human CHOP. Whereas GCN2-Xrp1 signaling suppresses translation and overall metabolism in damaged enterocytes, it also induces an IL-6-like cytokine, Upd3, which activates nearby ISCs for regenerative growth. This GCN2/Xrp1 pathway operates in parallel with other stress sensing systems, including p38MAPK, JNK, and Hippo/Yki, to regulate stem cell activities, regeneration, and gut homeostasis. Similar regulation likely operates in regenerative human epithelia.