The laboratory is interested in the regulation of stem cells activity in physiological and pathological contexts, and we have chosen the hematopoietic compartment and the liver as working models.
We study the mechanisms that regulate various aspects of stem cell biology, including cell cycle regulation, the decision to self-renew or differentiate into more mature cells, and interactions between stem cells and their niches. While hematopoietic stem cells are well described and serve as a paradigm to study stem cells from other biological systems, the liver stem/progenitor cell compartment is poorly characterized, and the contribution of stem cells to liver development and homeostasis is a subject of intense debate. We are developing several approaches, including new lines of transgenesis, to identify populations of stem and progenitor cells throughout different steps of development (from embryogenesis to adult liver) and we intend to characterize these populations, in order to identify a spatio-temporal hierarchy between them and understand their contribution to liver biology.
In addition, we investigate the mechanisms that promote the aberrant activity of stem cells, and the development of various types of cancer that originates from the stem cell compartment. In particular, we are developing an important research effort to characterize the role of the Rb pathway in the regulation of stem cells activity. The Rb family of genes includes Rb (the first identified tumor suppressor gene), p130 and p107, and is a central component of the Rb pathway. Genetic or epigenetic events targeting various components of the Rb pathway have been identified in the vast majority of cancers of diverse origin, and an important consequence of these events is the functional inactivation of the Rb family of proteins. However, mechanisms of tumorigenesis upon functional alteration of the Rb pathway are poorly understood, and we have recently shown that the stem cell compartment is particularly sensitive to loss of Rb family of genes. We have developed several mouse models to investigate the role of the Rb family of genes in the control of hematopoietic and liver stem cells activity, and we use a combination of bioinformatic analysis, in vitro, ex vivo and in vivo approaches to characterize the molecular and cellular mechanisms of tumorigenesis upon alteration of the Rb pathway in the liver (hepatocellular carcinoma) and the blood (myeloid disorders).
Education and Training
MS - University of Liège, Liège, Belgium
BS in Pharmacy - University of Liège, Liège, Belgium
PhD - University of Liège, Liège, Belgium
Postdoctoral Fellowship - Stanford University, Stanford, CA
Postdoctoral Fellowship - University of Liège, Liège, Belgium
Titles and Academic Titles
Assistant Professor of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania
Hematopoietic stem cell biology
Liver stem/progenitor cell biology
Retinoblastoma (Rb) gene and the Rb pathway
Garfin P, Min D, Bryson J, Serwold T, Edris B, Blackburn CC, Richie E, Weinberg K, Manley N, Sage J and Viatour P: Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression. Journal of Experimental Medicine in press, 2013.
Viatour P: Bridges between Cell Cycle Regulation and Self-Renewal Maintenance. Genes and Cancer in press, 2013.
Viatour P, Elhmer U, Saddic L, Dorrell C, Andersen JB, Lin C, et al. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J Exp Med. 2011 Sept 26;208(10):1963-76.
Viatour P, Sage J. Newly identified aspects of tumor suppression by RB. Dis Model Mech. 2011 Sept; 4(5): 581–585.
Arnold CP, Tan R, Zhou B, Yue SB, Schaffert S, Biggs JR, et al. MicroRNA programs in normal and aberrant stem and progenitor cells. Genome Res. 2011 May; 21(5):798-810.
Wirt SE, Adler AS, Gebala V, Weimann JM, Schaffer BE, Saddic LA, et al. G1 arrest and differentiation can occur independently of Rb family function. J Cell Biol. 2010 Nov 15;191(4):809-25.
Keutgens A, Zhang X, Shostak K, Robert I, Olivier S, Vanderplasschen A, et al. Bcl-3 degradation involves its polyubiquitination through a FBW7-independent pathway and its binding to the proteasome subunit PSMB1. J Biol Chem. 2010 Aug 13; 285(33):25831-40.
Keutgens A, Shostak K, Close P, Zhang X, Hennuy B, Aussems M, et al. The repressing function of the oncoprotein Bcl-3 requires CtBP while its polyubiquitination and degradation involve the E3 ligase TBLR1. Mol Cell Biol. 2010 Aug;30(16):4006-21.
Burkhart DL, Ngai LK, Roake C, Viatour P, Thangavel C, Ho VM, et al. Regulation of Rb transcription in vivo by Rb family members. Mol Cell Biol. 2010 Apr;30(7):1729-45.
Robert I, Aussems M, Zhang X, Keutgens A, Hennuy B, Viatour P, et al. MMP9 induction by a truncated oncogenic NF-kB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes. Oncogene. 2009 Apr 2;28(13):1626-38.
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