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[Seminar Notification] Dr. Dae-Sik Lim_12.01.2016
2016-11-30

1. Title : Hippo signaling and Adult Stem Cell

2. Speaker : Dae-Sik Lim, Ph.D.

3. Affiliation : National Creative Research Initiatives Center, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)

4. Date : 12. 01. 2016 16:00-17:00

5. Place : SIMS Main Building, Auditorium 109 (1F)

6. Abstract :

The Hippo signaling pathway has emerged as a mediator of tumor suppression that is evolutionarily conserved from flies to humans. The core complex of the Hippo pathway consists of the protein kinase Hippo (MST1 and MST2 in mammals), Salvador (SAV1 or WW45), Mats (MOB1), the protein kinase Warts (LATS1 and LATS2) and transcription activator Yorkie (YAP and TAZ). Mice with genetic disruption of the Hippo pathway show two key features: expansion of tissue-specific stem /progenitor cell populations, and a hyper-regenerative response and increased cancer incidence after tissue damage. Thus, Hippo pathway restricts stem/progenitor cell proliferation during epithelial development by inhibiting YAP/TAZ activity. Of interest, Hippo pathway mutant mice showed mechanistically and histologically distinct phenotypes in the liver.

In recent, we newly generated mice with liver-specific deletion of Lats1 and Last2. These mice showed expansion of ductal plate cells (biliary cells) with YAP hyperactivation and severe hepatic damages. Loss of Lats1/2 promotes biliary cell proliferation and differentiation whereas Lats1/2 deletion blocks hepatocyte differentiation from hepatoblast. We will discuss how Hippo signaling affects cell fate determination and differentiation of hepatic stem/progenitor cells during liver development. Additionally, we will discuss how YAP activity is regulated and what downstream targets of YAP endow cancer stem cell properties and their oncogenic activity.