Lab: Gastrointestinal Translational Research Lab
Advisor: Dr. Agnieszka Bialkowska
The GI Translational Research Lab focuses on studying the mechanisms regulating the regenerative capacity of the intestinal epithelium upon injury. The intestinal epithelium is organized into two connected structures: proliferative invaginations known as crypts of Lieberkühn and differentiated protrusions extending from the crypt known as villi. Intestinal stem cells (ISCs) and differentiated cells supporting ISCs form the crypts. At the base of the crypt lie active ISCs (aISCs) which are sensitive to radiation injury, and quiescent reserve ISCs (rISCs), which are activated upon radiation injury. Stromal cells are found directly under the crypts and are critical for tissue homeostasis.
A subpopulation of rISCs, marked by Bmi1, are a source for regeneration after injury. The intestinal epithelium regenerates through three distinct phases: apoptosis, proliferation, and normalization, where the epithelium is restored to pre-irradiation conditions (Fig. 1).
Chromatin accessibility and gene expression analysis can reveal epigenetic changes occurring in a temporal- and region-specific manner to understand microenvironmental influences on crypt regeneration. I conducted analysis of open chromatin sequencing data (ATAC-Seq), which revealed robust WNT signaling at the onset of injury, followed by a significant reduction in WNT activity at 24 hours and a return to elevated WNT signaling at 96 hours. The exact role of stromal cells in regulating WNT signaling and supporting epithelial regeneration immediately upon injury is not fully understood. My research aims to address this gap by identifying crucial WNT pathway components in epithelial and stromal cells driving the first 24 hours of epithelium response after radiation injury.
It is important to understand the mechanisms of activation of signaling pathways involved in regeneration to better aid in preventing and treating injuries to the gut caused by radiation therapy, chemotherapy, and inflammatory diseases. This work could pave the way for novel interventions promoting tissue repair and improving patient outcomes in a wide range of gastrointestinal injuries.
