Open Research Projects, Research

The human assembloid reveals the crosstalk of colonic resident macrophages with their neighboring epithelium, vasculature, and enteric nervous system

Principal Investigator

Prof. Dr. Michael Sigal

Scientific interest within the context of the graduate college:

Our lab investigates the gastrointestinal (GI) tract epithelium – the cellular layer lining the stomach and intestine that forms a vital barrier between the body and the external environment. A central focus lies on understanding the mechanisms of epithelial regeneration and how interactions with commensal microbiota and pathogenic bacteria influence this process, potentially leading to inflammation, gut dysfunction, or cancer.

Project description:

The crypt-villus architecture of the intestinal mucosa is underpinned by dynamic interactions between distinct populations of epithelial, stromal, and immune cells. While the epithelial compartment has garnered significant attention, there is a growing appreciation for the critical role of mesenchymal cells in shaping epithelial stem cell function and dictating lineage specification in homeostasis and upon perturbation.

We hypothesize that similar processes are co-opted in the context of carcinogenic transformation, that in contrast to the traditional view does not simply rely on mutational events but instead emerges as a result of a dynamic interplay between epithelium and stroma. Using a model of gastric cancrinogenesis that integrates mutational and environmental cues we aim to explore this process in detail and would like to integrate a doctoral thesis into this project.

Aim 1: To characterize the microenvironemnt in a murine model of gastric cancer.

Aim 2: To functionally determine key stromal drivers of epithelial transformation in the stomach.

Aim 3: To explore the relevance of the identified pathways in a cohort of patients with gastric cancer.

Application details

References

  1. Wizenty J and Sigal M. Helicobacter pylori, microbiota and gastric cancer – principles of microorganism-driven carcinogenesis. Nat Rev Gastroenterol Hepatol. 2025; 22(5):296-313.
  2. Fischer AS, Müllerke S, Arnold A, Heuberger J, Berger H, Lin M, […], Horst D, Tacke F, Sigal M. R-spondin/YAP axis promotes gastric oxyntic gland regeneration and Helicobacter pylori-associated metaplasia in mice. J Clin Invest. 2022; 132(21):e151363.
  3. Wizenty J, Müllerke S, Kolesnichenko M, Heuberger J, Lin M, Fischer AS, […], Berger H, Tacke F, Sigal M. Gastric stem cells promote inflammation and gland remodeling in response to Helicobacter pylori via Rspo3-Lgr4 axis. EMBO J. 2022; 41(13):e109996.
  4. Kapalczynska M, Lin M, Maertzdorf J, Heuberger J, Muellerke S, Zuo X, […], Tacke F, Meyer TF, Sigal M. BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation. Nat Commun. 2022; 13(1):1577.