Home | News | Directories | Calendar | Maps | Contact Us | Webmail
Perelman School of Medicine at the University of Pennsylvania Advanced Search

Patrick M Viatour, Pharm.D, PhD

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
Education:
BS (Pharmacy)
University of Liege, Belgium, 1998.
Master (of Science)
University of Liege, Belgium, 1999.
PhD
University of Liege, Belgium, 2004.
Permanent link
 
Perelman School of Medicine > Faculty > Search

Description of Research Expertise

Keywords:
Epigenetic
Stem Cells & Cancer

Research Overview:
The long-term goal of my lab is to determine the mechanisms that transform adult stem cells into the cell of origin for many types of cancer. In particular, we study the epigenetic mechanisms that drive tumor initiation and progression upon loss of major tumor suppressor genes such as the Rb genes family.

This family, which includes Rb, p130 and p107, plays a central role in the regulation of cell cycle activity by sequestering E2F transcription factors. Cellular exposure to mitotic stimuli leads to the functional inactivation of Rb family proteins. Consequently, E2F factors are released and transactivate a large set of genes that collectively promote the progression through cell cycle. Genetic and epigenetic events targeting various components of the Rb pathway have been identified in the vast majority of cancers. A common and important consequence of these events is the permanent inactivation of Rb family, therefore establishing Rb family genes as major tumor suppressor genes. However, besides aberrant proliferation, the mechanisms that drive tumorigenesis upon Rb family inactivation remain mostly unknown.

To determine these mechanisms and identify critical drivers of tumorigenesis for translational purposes, we have generated new mouse models that recapitulate the acute Rb family inactivation observed in cancer and have chosen hematopoiesis and the liver as experimental systems. Our recent data (Cell Stem Cell 2008, JEM 2011 & 2013) have demonstrated that stem cells, in contrast to terminally differentiated cells, are particularly sensitive to Rb family loss. Indeed, Rb family deficient stem cells rapidly exhibit a complex phenotype including proliferation, biased differentiation and tumorigenesis. Complementary molecular approaches have started to unravel new and surprising means for E2F factors, including the recruitment of complex epigenetic mechanisms, to activate important oncogenic features that drive tumor progression.

Our current research effort aims at identifying these epigenetic mechanisms and developing compound-based strategies to inactivate them and impair tumor development. To this end, we are developing several mouse models and using a combination of bioinformatic analysis, as well as in vitro, ex vivo and in vivo approaches.

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.

back to top
Last updated: 10/02/2014
The Trustees of the University of Pennsylvania