The intestine constantly repairs itself with stem cells, but when those cells receive the wrong signals, they can drive cancer instead of healthy tissue. Researchers have discovered that the intestine does far more than digest food—it acts as a central coordinator, sending signals that influence organs throughout the body. Yet the fundamental rules governing how stem cells balance repair, regeneration, and tumour formation remain largely unknown. This project aims to crack that code by studying three specific mechanisms: how stem cells change their internal metabolism during regeneration and cancer, how the intestine talks to its surrounding blood vessels to influence disease, and how special hormone-producing cells in the gut send signals that affect the whole body. The work is fundamental science—it will not produce a drug or therapy tomorrow. But understanding these core processes could eventually reveal new targets for treatments that either boost intestinal repair after injury or block the signals that drive cancer, potentially leading to therapies that treat the intestine and its systemic effects together rather than in isolation.
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The adult intestine is a major barrier epithelium and coordinator of multi-organ functions. 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 these signals integrate to control intestinal and whole-body homeostasis is largely unknown. Addressing this gap in knowledge is central to an improved understanding of intestinal pathophysiology and its systemic consequences. Combining Drosophila and mammalian model systems my laboratory has discovered fundamental mechanisms driving intestinal regeneration and tumourigenesis and outlined complex inter-organ signalling regulating health and disease. Building upon new findings from our research, here we propose to: - Identify and characterise stem cell intrinsic metabolic adaptations underpinning intestinal regeneration and tumourigenesis. - Elucidate interactions between the intestine and its vascular microenvironment influencing intestinal regeneration and tumourigenesis. - Characterise the role of enteroendocrine signals in the intestine and the whole-body in health and disease. The work outlined in this proposal will reveal new drivers of intestinal regeneration and cancer and key processes through which the intestine coordinates multi-organ responses. This knowledge holds great potential to inform the design of integrative regenerative and anti-cancer therapies.
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