Dr Bon-Kyoung Koo
Homeostatic regulation of adult stem cells
Cambridge Stem Cell Institute, Gleeson Building
Bon-Kyoung Koo has the unique experience of studying the role of endosomal E3 ubiquitin ligases in two major signalling pathways, which makes him a leading expert in this field. He is an experienced mouse geneticist with broad experience in the field of E3 ubiquitin ligases.
Bon-Kyoung participates in the Marie Curie Initial Training Network "WntsApp" and was recently awarded with the Sir Henry Dale Fellowship (2013) and ERC starting grant (2015).
ERC, Wellcome Trust, Royal Society, Marie Curie
Homeostatic turnover in adult tissues is governed by the interplay of a multitude of signalling pathways. Upon tissue damage, adult stem cells rapidly proliferate to restore the loss and reinstate homeostasis; regulatory signalling that governs proliferation and differentiation of stem cells enable this damage response. De-regulation of these processes on the other hand results in either hyperplasia or loss of stem cells. Dr Koo investigates the role of an important class of modulators – E3 ubiquitin ligases – in tissue homeostasis. He has found two important regulators – Mib1 and RNF43. Mib1 has a crucial role in Notch ligand activation in niche cells and RNF43 attenuates Wnt activation in intestinal stem cells. His research focuses on additional E3 ubiquitin ligases that have an important role in stem cell – niche interactions in adult tissues.
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Throughout life, our body needs constant renewal of cells to maintain our health. Modern biology and medical science have identified stem cells in most adult tissues as the source of this continuous regeneration. Our team aims to help answer these key questions: • How do adult tissue stem cells regulate the number of specialised cells? • How do adult tissue stem cells respond when tissue is damaged? We are learning that regeneration is tightly controlled by complex molecular signals and by the micro-environment, or ‘niche’, surrounding tissue stem cells. Specifically, we have identified that a group of proteins called E3 ubiquitin ligases (E3s) play an important role in regulating the signals that promote or inhibit regeneration. Currently, we are particularly interested in a type of dormant stem cell in the lining of the stomach. When the stomach tissue is damaged, these dormant stem cells are activated and they divide rapidly to replace lost cells. Studying this system is revealing fascinating new information about how the body repairs and regenerates.
- Koo BK*†, van Es JH*, van den Born M, Clevers H†. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant tumors PNAS. Jun 16;112(24):7548-50. PMCID:PMC4475934
- Schwank G*, Koo BK*, Sasselli V, Dekkers JF, Heo I, Demircan T, Sasaki N, Boymans S, Cuppen E, van der Ent CK, Nieuwenhuis EES, Beekman JM, Clevers H. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013 Dec 5;13(6):653-8. PMID:24315439
- Stange DE*, Koo BK*, Huch M, Sibbel G, Basak O, Lyubimova A, Kujala P, Bartfeld S, Koster J, Geahlen JH, Peters PJ, van Es JH, van de Wetering M, Mills JC, Clevers H. Differentiated Troy+ Chief Cells Act as Reserve Stem Cells to Generate All Lineages of the Stomach Epithelium. Cell. 2013 Oct 10; 155(2):357-368. PMCID:PMC4094146
- Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJR, Maurice MM, Clevers H. Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Nature 2012 Aug 30;488(7413):665-9. PMID:22895187
- Koo BK*, Lim HS*, Song R, Yoon MJ, Yoon KJ, Moon JS, Kim YW, Kwon MC, Yoo KW, Kong MP, Lee J, Chitnis AB, Kim CH, Kong YY. Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development. 2005 Aug;132(15):3459-70. PMID:16000382