Dawang ZHOU, Ph.D.
1998, B.Sc., Xiamen University;
2002, M.Sc., City University of New York-Graduate Center;
2006, Ph.D., Albert Einstein College of Medicine, New York.
2006-2009, Postdoctoral Fellow at Massachusetts General Hospital, Harvard Medical School;
2009-2011, Instructor in Medicine, Harvard Medical School;
2011-present, Principal Investigator, School of Life Sciences, Xiamen University;
2012-present, vice dean, School of Life Sciences, Xiamen University.
The Hippo pathway has emerged as a critical developmental pathway contributing to processes that regulate tissue growth and organ size. Our research group aims to characterize the regulation and physiologic functions of the Mst1 and Mst2 protein kinases, which are the mammalian orthologs of the “hippo” kinase. Recently, we have made several exciting discoveries regarding the physiological functions of these two kinases. At first, we conditionally deleted both of Mst1 and Mst2 in the developing mouse liver. Within a few weeks, these mice exhibit a dramatic expansion of undifferentiated cells that resemble bipotential liver progenitors. Remarkably, these mice invariably go on to develop both hepatocellular carcinoma and cholangiocarcinoma within four months. In addition, the combined deletion of Mst1 and Mst2 from the hematopoietic compartment results in the absence of all peripheral lymphocytes and a profound immunodeficiency syndrome. The liver phenotype reflects an essential, overlapping function of Mst1 and Mst2 in the negative regulation of liver cell proliferation, whereas the lymphocyte cell phenotype reflects predominantly the loss of Mst1/2-mediated regulation of cell adhesion and migration. The identification of the molecular elements upstream and downstream of the Mst1/2 kinases for each of these functions is the focus of present effort.
1. Geng J, Sun X, Wang P, Zhang S, Wang X, Wu H, Hong L, Xie C, Li X, Zhao H, Liu Q, Jiang M, Chen Q, Zhang J, Li Y, Song S, Wang HR, Zhou R, Johnson RL, Chien KY, Lin SC, Han J, Avruch J, Chen L*, Zhou D*.Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nature Immunol. 2015. doi: 10.1038/ni.3268.
2.Wu H, Wei L, Fan F, Ji S, Zhang S, Geng J, Hong L, Fan X, Chen Q, Tian J, Jiang M, Sun X, Jin C, Yin ZY, Liu Q, Zhang J, Qin F, Lin KH, Yu JS, Deng X, Wang HR, Zhao B, Johnson RL, Chen L*, Zhou D*. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nature Commun, 2015; 6: 6239. doi: 10.1038/ncomms7239.
3.Wu H, Xiao Y, Zhang S, Ji S，Wei L, Fan F, Geng J, Tian J, Sun X, Qin F, Jin C, Lin J, Yin Z, Zhang T, Luo L, Li Y, Song S, Lin SC, Deng X, Camargo F, Avruch J, Chen L*, Zhou D*. The Ets transcription factor GABP is a component of the Hippo pathway essential for growth and antioxidant defense. Cell Reports, 2013; 3(5): 1663-77.
4. Mou F, Praskova M, Xia F, Van Buren D, Hock H, Avruch, J*, Zhou D*. The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J Exp Med. 2012; 209(4): 741-59.
5. Zhou D*. Diversity in function and regulation of the Hippo pathway. Cell Biosci. 2013; 3(1): 34.
6.Hong L, Cai Y, Jiang M, Zhou D*, Chen L*.The Hippo signaling pathway in liver regeneration and tumorigenesis. Acta Biochim Biophys Sin. 2015; 47(1): 46-52.
7.Chen L, Qin F, Deng X, Avruch J, Zhou D*. Hippo pathway in intestinal homeostasis and tumorigenesis. Protein Cell. 2012; (4): 305-10.
8.Qin F, Tian J, Zhou D*, Chen L*. Mst1 and Mst2 kinases: regulations and diseases. Cell Biosci. 2013; 3(1): 31.
9. Matsumoto H, Murakami Y, Kataoka K, Lin H, Connor KM, Miller JW, Zhou D, Avruch J, Vavvas DG. Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment. Cell Death Dis. 2014 5: e1269.
10. Gao T, Zhou D, Singh T, Yang C, Mendez AP, Maddipati R, Tzatsos A, Bardeesy N, Avruch J, Stanger B*. Hippo Signaling Regulates Differentiation and Maintenance in the Exocrine Pancreas. Gastroenterology. 2013; 144(7): 1543-1553.
11. Zhou D, Zhang Y, Wu H, Yi Y, Lawrence E, Dawson D, Willis J, Markowitz S, Camargo F，Avruch J*. The Mst1 and Mst2 kinases suppress intestinal stem cell proliferation and tumorigenesis by inhibiting Yap overabudance. Proc Natl Acad Sci U S A. 2011; 108(49): E1312-20.
12.Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez R, Zhou D, Kreger B, Vasioukhin V, Avruch J, Brummelkamp T, Camargo F*. Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell. 2011; 144(5): 782-95.
13. Zhou D, Conrad C, Park J, Xia F, Payer B, Lauwers G, Thasler W, Lee J, Avruch J*, Bardeesy N*. Mst1 and Mst2 maintain hepatocyte quiescence and suppress the development of hepatocellular carcinoma through inactivation of Yap1 oncogene. Cancer Cell. 2009; 16: 425-38.
14. Zhou D, Medoff BD, Chen L, Li L, Zhang XF, Praskova M, Liu M, Landry A, Blumberg RS, Boussiotis VA, Xavier R, Avruch J*. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of na?ve T cells. Proc Natl Acad Sci U S A. 2008; 105(51): 20321-6.