Patrick M Viatour, Pharm.D, PhD

faculty photo
Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Children's Hospital of Philadelphia
Colket Translational Research Building, Rm 4064
3501 Civic Center Blvd
Philadelphia, PA 19104
Office: 267-425-3004
BS (Pharmacy)
University of Liege, Belgium, 1998.
Master (of Science)
University of Liege, Belgium, 1999.
University of Liege, Belgium, 2004.
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Description of Research Expertise

RB/E2F signaling module
Liver cancer/HepatoCellular Carcinoma (HCC)
Hematopoietic Stem Cell (HSC) biology
Mouse models

Research Overview:
The Rb family of genes, which includes Rb, p130 and p107, is a central component of the Rb pathway. In quiescent cells, Rb family members interact with E2F factors and repress their transactivation activity. Cellular exposure to mitotic stimuli leads to the functional inactivation of Rb family proteins and the subsequent release of E2F family factors. Consequently, E2F factors transactivate a large set of genes that collectively promote the progression through cell cycle. Not surprisingly, genetic and epigenetic events targeting various components of the Rb pathway have been identified in the vast majority of cancers. An important consequence of these events is the permanent functional inactivation of Rb proteins and aberrant proliferation associated with sustained E2F activity.
In addition to this well-established model, our recent data (Cell Stem Cell 2008, JEM 2011 & 2013) have demonstrated that E2F factor activity extends beyond the sole regulation of cell cycle to include non-cell cycle functions that appear to be critical in various physio-pathological contexts, including tumorigenesis. However, the identity and roles of these non-cell cycle functions, as well as their mode of transactivation by E2Fs, are still mostly undetermined. In our laboratory, we aim to characterize the non-canonical functions of E2F factors in two distinct biological systems, the blood and the liver. To this end, we are developing several mouse models and use a combination of bioinformatic analysis, in vitro, ex vivo and in vivo approaches.
In the liver, our previous data have shown that Rb family loss leads to the development of HepatoCellular Carcinoma (HCC) and our current research effort investigates the role of E2F factors in this tumorigenic setting. In particular, we intend to identify the multiple oncogenic features that are activated by E2F factors during HCC progression, as well as the transcriptional mechanism that underlies their activation in this context.
In the hematopoietic system, we have shown that Rb family loss induces a striking phenotype in Hematopoietic Stem Cells (HSCs), including sustained proliferation and biased differentiation, leading to the accumulation of mature myeloid cells. We intend to identify the role of E2F factors in this complex phenotype in order to design strategies to uncouple these various biological functions for therapeutic purposes.
Graduate students interested in rotating in the lab should contact Dr. Viatour for additional information on the research projects currently developed.

Lab members:
Rebecca Teng, Research Assistant
Nathanael Lo, Research Assistant
Eunsun Kim, Graduate Student
Elizabeth Gillespie, Postdoc
Ariella Sasson, Bioinformatician
Kathryn Wurges, Administrative Assistant

Selected Publications

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 210 (6): 1087-97, 2013.

Viatour P and Sage J: Newly identified aspects of tumor suppression by Rb. Disease Models and Mechanisms 4 (5), 2011.

Viatour P, Saddic L, Elhmer U, Lin C, Dorrell C, Andersen JB, Schaffer B, Ostermeier A, Vogel H, Sylvester KG, Thorgeirsson SS, Grompe M, and Sage J.: Notch signaling suppresses hepatocellular carcinoma initiated from mouse adult liver progenitors following inactivation of the Rb family. Journal of Experimental Medicine 208 (10): 1963-76, 2011.

Wirt SE, Adler AS, Gebala V, Weimann JM, Schaffer BE, Saddic LA, Viatour P, Vogel H, Chang HY, Meissner A, Sage J.: G1 arrest and differentiation can occur independently of Rb family function. J Cell Biol. 191(4): 809-25, 2010.

Viatour P, Somervaille TC, Venkatasubrahmanyam S, Kogan S, McLaughlin ME, Weissman IL, Butte AJ, Passegue E and Sage J.: Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family. Cell Stem Cell 3(4): 416-428, 2008.

Kotake Y, Cao R, Viatour P, Sage J, Zhang Y, Xiong Y.: pRb family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes and Development 21(1): 49-54, 2007.

Viatour P, Merville MP, Bours V and Chariot A.: Phosphorylation of NF-κB/IκB proteins: implications in cancer and inflammation. Trends in Biochemical Sciences 30(1): 43-52, 2005.

Viatour P, Dejardin E, Warnier M, Lair F, Claudio E, Bureau F, Marine JC, Merville MP, Maurer U, Green DR, Piette J, Siebenlist U, Bours V and Chariot A.: GSK3-mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity. Molecular Cell 16(1): 35-45, 2004.

Viatour P, Bentires-Alj M, Chariot A, Deregowski V, de Leval L, Merville MP and Bours V.: NF-kappaB2/p100 induces Bcl-2 expression. Leukemia 17(7): 1349-1356, 2003.

Viatour P, Legrand-Poels S, Van Lint C, Warnier M, Merville MP, Gielen J, Piette J, Bours V and Chariot A.: Cytoplasmic IkappaBalpha increases NF-kappaB independent transcription through binding to HDAC1 and HDAC3. Journal of Biological Chemistry 278(47): 46541-46548, 2003.

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Last updated: 09/05/2014
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