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Intestinal stem cells • organoids • hippo signaling • tissue regeneration and cancer
One of the extraordinary abilities of all living creatures is their capacity to repair damaged tissues following injury. This regenerative property is in large part due to the existence of stem cells that are defined by their ability to replace themselves through division, as well as giving rise to specialized cell types through a process known as differentiation. Unfortunately, once stem cells acquire mutations that cause them to proliferate incessantly, they can also fuel cancer growth. My lab focuses on the stem cells in the epithelial lining of our intestinal tract. By constantly replenishing the gut epithelium, intestinal stem cells ensure proper nutrient uptake and barrier formation against environmental toxins and pathogens throughout life. My interests lie in understanding the signals that control gut stem cell behaviour and how these signals become misregulated in diseases such as inflammatory bowel disease and colon cancer.
Gregorieff A, Wrana JL. Hippo signaling in intestinal regeneration and cancer. Curr Opin Cell Biol. 2017 May 18;48:17-25. PMID: 28527754.
Gregorieff A, Liu Y, Inanlou MR, Khomchuk Y, Wrana JL. Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer. Nature. 2015 Oct 29;526(7575):715-8. PMID: 26503053.
Gregorieff A, Stange DE, Kujala P, Begthel H, van den Born M, Korving J, Peters PJ, Clevers H. The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium. Gastroenterology. 2009 Oct;137(4):1333-45. PMID: 19549527.
Gregorieff A, Pinto D, Begthel H, Destrée O, Kielman M, Clevers H. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology. 2005 Aug;129(2):626-38. PMID: 16083717.
van Es JH, Jay P, Gregorieff A, van Gijn ME, Jonkheer S, Hatzis P, Thiele A, van den Born M, Begthel H, Brabletz T, Taketo MM, Clevers H. Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat Cell Biol. 2005 Apr;7(4):381-6. PMID: 15778706.