Dr Bon-Kyoung Koo
Homeostatic Regulation of Adult Stem Cells
Wellcome Trust - MRC Cambridge Stem Cell Institute
• Roxana Micsik (Post-Doc) • Ya-Lin Huang (Post-Doc) • Amanda Andersson-Rolf (MRC PhD Student) • Juergen Fink (WT PhD Student) • Alessandra Merenda (MC ITN PhD Student) • Gianmarco Mastrogiovanni (MC ITN PhD Student)
Dr Bon-Kyoung Koo started his research group at the Wellcome Trust - MRC Cambridge Stem Cell Institute (CSCI) in 2013. During his career development, he identified the role of two endosomal E3 ubiquitin ligases in two major signalling pathways (Mib1 in Notch and RNF43/ZNRF3 in Wnt signalling), which makes him a leading expert in this field. Based on his mouse genetics background, he then contributed to the identification of novel Troy+ stomach stem cell population and to the development of CRISPR/Cas-mediated gene correction method in 3D human colonic organoid culture. After joining CSCI, he aims to understand the homeostatic regulation of adult tissues. Functional genetics of E3 ubiquitin ligases, multi-color lineage tracing, and in vitro genetics in 3D gut organoid culture are the main approaches of his lab. His lab is part of the Marie Curie Initial Training Network "WntsApp". His team is currently supported by Sir Henry Dale Fellowship from Wellcome Trust and Royal Society. In 2015, he received prestigious ERC starting grant to study how the stomach epithelium maintains its integritiy in homeostasis and injury-repair.
Homeostatic turnover in adult tissues is governed by the interplay of a multitude of signalling pathways that are often triggered by niche cells providing diverse ligands to support stem cells. 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. In the intestine, fine-tuning of this regulation is carried out not only by crosstalk between different pathways, but also by modulation of activity within individual pathways at several levels. An important class of modulators are E3 ubiquitin ligases. In cells, E3 ligases commonly promote degradation of their target proteins by proteasomes. At the plasma membrane, however, E3 ligases regulate levels of transmembrane proteins by promoting ubiquitin-dependent endocytosis. Mib1, an E3 for Notch ligands, has a crucial role in Notch ligand activation in niche cells that, in turn, promotes Notch signalling in stem cells (Development 2005, Neuron 2008, and Gastroenterology 2009). RNF43 and ZNRF3 attenuate Wnt activation in intestinal stem cells by functioning as E3s for Wnt receptors (Nature 2012). Thus to date, we have learned about E3 ligases working in the Notch and Wnt pathways in adult stem cells. In light of this, it seems probable that other E3 ligases, with important roles in adult stem cell biology, remain to be identified. Our research focus is on identifying and understanding the role of novel E3 ubiquitin ligases in homeostatic regulation of stem cells.
We have identified a novel quiescent Troy+ epithelial stem cell population in the stomach. Upon tissue damage, Troy+ stem cells actively divide to regenerate lost cell types. The discovery of Troy+ stomach stem cells enables us to investigate how an adult tissue can retain its homeostasis after various types of injury. This study will help us understanding how homeostasis is achieved in the adult stomach and in other tissues, which will potentially lead to the development of successful adult stem cell therapy.
ERC-funded postitions will be available from mid 2015.
We are looking for talented post-doc and PhD candidates. Please contact Dr Bon-Kyoung Koo for any enquiry (firstname.lastname@example.org).
For students planning to join our lab
A 'Must-Read' before you apply:
I will only consider those who made a deep thought about joining my lab.
Review: Stem cells marked by the R-spondin receptor LGR5
We are part of the Marie Curie Initial Training Network "WntsApp"
Awards & Grants
Sir Henry Dale Fellowship (by the Wellcome Trust & the Royal Society)
ERC starting grant (by European Research Council)
Plain EnglishThroughout our 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 continuous source of regeneration. Interestingly, these stem cells require tight control to allow the production of new cells only in appropriate conditions. Among many regulators, E3 ubiquitin ligases (E3s) are genuine sweepers in cells. These molecules clean other proteins that are no longer required for growth and function of stem cells.
Schwank G*, Koo BK* et al. 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. F1000
Stange DE*, Koo BK* et al. 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 F1000
Koo BK et al. Tumour suppressor RNF43 is a stem cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012 Aug 30;488(7413):665-9. F1000
Kim HA*, Koo BK* et al. Notch counteracts Wnt-beta-catenin signaling through chromatin modification in mouse and human colorectal cancer J Clin Invest. 2012 Sep 4;122(9):3248-59.
Koo BK*, Stange DE* et al. Controlled gene expression in primary Lgr5 organoid cultures Nature Methods. 2011 Dec 4;9(1):81-3.
Koo BK*, Lim HS* et al. Notch signaling promotes the generation of EphrinB1-positive intestinal epithelial cells. Gastroenterology. 2009 Jul;137(1):145-55.
Koo BK*, Lim HS* et al. Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development. 2005 Aug;132(15):3459-70.