Research Summary
Epithelial tissues are exposed to dynamic cellular environments, which can include potential toxins, infectious material, and sources of physical injury. Tissue resident stem cells maintain epithelial function throughout life by balancing differentiation and self-renewal via precisely regulated gene expression programs. Direct injury to or loss of these stem cells can cause partially differentiated or mature epithelial cells to “dedifferentiate” or return to a stem cell-like state. Our lab is interested in understanding how transcription factors and chromatin regulatory networks contribute to this context-dependent ability of epithelial cells to exhibit stem cell properties, which may also be important in development and tumorigenesis.
Relevance of Research to CGIBD Mission:
The Gracz Lab studies two gastrointestinal epithelial tissues with distinct functional characteristics: the intestine and liver. While the intestinal epithelium is rapidly proliferative and replaced regularly by intestinal stem cells (ISCs) throughout adult life, the biliary epithelial cells (BECs) and hepatocytes that make up the liver epithelium are largely quiescent in the absence of injury. While both tissues exhibit remarkable potential for cellular plasticity, repair, and regeneration, the liver accomplishes these processes without a dedicated stem cell pool. We seek to advance mechanistic understanding of the gene regulatory networks required for epithelial development, renewal, and regeneration in functionally distinct tissues. Our long-term goal is to identify gene regulatory relationships that may improve the diagnosis and treatment of developmental disorders, chronic inflammatory disease, and cancer.
CGIBD Focus Area(s): Regenerative Medicine/Repair
Pilot and Feasibility Award 2016, 2020
Collaborators: Burclaff, Diehl, Magness, McCauley, van Landeghem
