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Patrick M. Viatour, PharmD, PhD

Assistant Professor of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania

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).

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