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Welcome to the Koo lab

Throughout life, our organs require constant cell renewal in order to remain functional. Modern biology and medical science have identified stem cells in adult tissues as the source of this continuous self-renewal. However, important key questions remain:

  • How do adult tissue stem cells regulate the ratio between stem cells and specialized, differentiated cells during homeostasis?
  • How do adult tissue stem cells respond to tissue damage and restore homeostasis?

We are learning that regeneration is tightly controlled by complex molecular signals.  Specifically, negative feedback regulation via post-translational control of proteins plays a crucial role in maintaining adult tissue integrity as well as adult stem cell activity.

By studying the cellular and molecular behaviour of intestinal and gastric adult stem cells during homeostasis and following injury repair, we hope to answer these outstanding questions.

Vision

We are fascinated by the adult stem cells and mechanisms responsible for maintaining organ function throughout life.

What is the identity of these cells? Does it change upon injury?

What are the regulatory mechanisms that control homeostatic turnover, and how do their perturbation contribute to disease progression?

We are driven by curiosity and aim to generate a creative working environment. New ideas as well as critical and constructive scientific discussions are always welcome as we work together to find the answers to the abovementioned questions.

Mission

We want to understand the cellular and molecular mechanisms that govern biological processes related to homeostatic turnover, tissue injury-repair and pre-neoplastic transformation.

Approach

To study the mechanisms regulating adult stem cells, we perform functional genetic studies using in vitro and in vivo models in combination with biochemical analyses and mathematical modelling.

In particular, we use transgenic mice in combination with lineage tracing approaches (whole-body, tissue-specific CreERT2 lines, and cell-type specific ablation models) to monitor the behaviour of intestinal and gastric adult stem cells during homeostasis and injury repair.

In addition, we use mouse and patient-derived 3D organoids as a screening platform to identify new players regulating adult stem cells. Diverse genetic tools developed in the lab allow us to further investigate the role of these novel candidates by gain- and loss-of-function studies in organoids, combined with biochemical approaches.

Impact

We are hoping to identify and understand the regulatory mechanisms that maintain homeostatic turnover, and how they are perturbed upon injury and pre-neoplastic transformation. Insight into the mechanisms that regulate adult gastro-intestinal stem cells can aid in the prediction and prevention of disorders, and lead to novel therapeutic strategies to treat cancers and ulcers.

Selected Publications

Koo, BK., van Es, JH., van den Born, M., Clevers, H. (2015). Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia. Proc Natl Acad Sci U S A. 112(24):7548-50

Schwank, G., Koo, BK., Sasselli, V., Dekkers, JF., Heo, I., Demircan, T., Sasaki, N., Boymans, S., Cuppen, E., van der Ent, CK., Nieuwenhuis, EE., Beekman, JM., Clevers, H. (2013). Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 13(6):653-8

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. (2013). Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell. 155(2):357-68

Koo, BK., Spit, M., Jordens, I., Low, TY., Stange, DE., van de Wetering, M., van Es, JH., Mohammed, S., Heck, AJ., Maurice, MM., Clevers, H. (2012). Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 488(7413):665-9

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. (2005). Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development. 132(15):3459-70

Funding