Hans Clevers (Hubrecht I., UU) 3: Organoid Technology for Disease Modeling

https://www.ibiology.org/development-... Dr. Hans Clevers provides a historical perspective on the discovery of adult stem cells in the gut, and explains how his lab developed a technique to grow from a single stem cell an organoid or mini-organ, a structure that recapitulates the normal structure of the gut. In his first talk, Dr. Hans Clevers provides a historical perspective on the discovery of adult stem cells in the gut. They identified a Wnt-dependent, rapid proliferating population of cells at the bottom of the crypt which seemed to be important for generating all epithelial cells in crypts and villi, and they hypothesized that these were gut stem cells. By using the Lgr5 gene as a marker, the Clevers’ lab confirmed that these long-lived cells were indeed the gut stem cells by showing that they were able to generate all of the cell types of the gut epithelium throughout life. Clevers characterizes the gut stem cells and its progenitors, and explains how his lab developed a technique to grow from a single stem cell an organoid or mini-organ, a structure that recapitulates the normal structure of the gut. In his second talk, Clevers shows how one can apply what we have learned from developing gut organoids to generate mini-organs for other epithelial tissues, like liver and lung. Clevers shows that these organoids have a similar expression profile as well as structural characteristics to those observed in real tissue. In addition, he shows how this technique can be used to generate non-mammalian organoids, like the development of venom gland organoids from snake venom gland tissue. As Clevers explains, such organoids can be used to discover possible novel therapeutics, including new anti-venom serum. In his third talk, Clevers describes how organoids can guide our understanding of disease progression in cancer. In addition, using Cystic Fibrosis and cancer as examples, Clevers shows how organoids can be used to predict therapeutic outcome in patients. Speaker Biography: Dr. Hans Clevers is a Principal Investigator at the Hubrecht Institute, a Professor in Molecular Genetics at the University Medical Center Utrecht, and an Oncode Investigator. He obtained his medical (1984) and doctoral (1985) degrees at the University of Utrecht. He continued his education as a post-doctoral fellow in the lab of Dr. Cox Terhorst at the Dana-Farber Cancer Institute at Harvard Medical School. In 1989, he joined the faculty at the University of Utrecht, where his lab studies the biology of Wnt signaling in development and cancer. Using Lgr5 as a marker, his lab discovered adult stem cells in the intestine, and developed a technique to grow these stem cells into epithelial organoids. Using these organoids, his lab is able to study a multitude of physiological, and pathological processes, and use organoids as a model to understand disease progression and predict drug responses. For his scientific contributions, Clevers received the Breakthrough Prize in Life Sciences in 2013, and is an elected member of the European Molecular Biology Organization (EMBO) (1999), the Royal Netherlands Academy of Sciences (2000), the National Academy of Sciences (2014), the French Academie des Sciences (2017) and the Royal Society of London (2019). Visit his lab website and learn more about Clevers’ research: https://www.hubrecht.eu/research-grou...