Prof. Julia Cordero
Beatson/Scotland Institute and University of Glasgow
Title: Interorgan communication through the adult intestine in health and disease.
Background: The adult intestine is a major barrier epithelium with vital endocrine, immune and metabolic roles, leading to the coordination of whole-body physiology. These functions are achieved by specialised cells such as absorptive enterocytes and secretory enteroendocrine cells, which are generated by intestinal stem cells (ISCs). Stem cells constantly repair the intestinal epithelium by adjusting their proliferation and differentiation to tissue intrinsic as well as micro- and macro-environmental signals. How do these signals integrate to preserve intestinal and whole-body health? Work in our laboratory is devoted to deciphering the cellular and molecular mechanisms regulating ISC behaviour during tissue regeneration and tumourigenesis. We are also interested in understanding how the intestine interacts with other tissues and organs to maintain organismal balance and how these interactions are deregulated in intestinal diseases such as cancer or inflammation. We use the fruit fly Drosophila melanogaster as our primary in vivo research model system combined with suitable mammalian paradigms. Our research aims to identify mechanisms that could be used in translational efforts to restore intestinal regeneration as well as to prevent malignant transformation of the intestine and alleviate the systemic consequences of intestinal malfunction.
Prof. Marco Milan
IRB Barcelona
https://www.irbbarcelona.org/en/research/marco-milan
Title: A tumour-host feed-forward loop contributes to malignant growth in chromosomal instability-induced epithelial tumours
Abstract: Chromosomal instability (CIN), characterized by frequent changes in chromosome number and structure, is common in human carcinomas and often leads to aneuploidy. Drosophila has been instrumental in demonstrating that CIN can promote tumour growth and malignancy through aneuploidy-induced senescence, a state marked by cell-cycle arrest and high secretory activity. Despite extensive chromosomal heterogeneity, I will present evidence that these cells share a distinct transcriptional program, with most responses to aneuploidy and senescence regulated at the transcriptional level. Nearly 10% of the most upregulated genes encode secreted proteins of the senescence-associated secretory phenotype (SASP). Five of these proteins act additively, locally or systemically, to block proliferation and induce cell death in neighbouring tissues. Our results indicate that this non-autonomous cell death feeds back to the tumour to enhance its growth, resembling super-competition and providing insight into tumour–host interactions relevant to human cancer.