My laboratory utilizes molecular and genetic approaches to study fundamental biological processes relevant to cancer pathogenesis. To this end, we utilize a broad array of technologies such as molecular, cellular and mouse genetics techniques. We focus our interests on the Promyelocytic leukemia tumor suppressor, oncogenic RAS, and the CK2 protein kinase. These genes control processes that are key in oncogenesis such as cell growth regulation, induction of apoptosis and oncogene-induced replicative senescence.
Characterization of the role of the Promyelocytic leukemia gene in tumor suppression:
PML is a tumor suppressor inactivated in acute promyelocytic leukemia and the essential component of the PML nuclear body, a macromolecular structure that consists of numerous proteins that play essential roles in cell regulation and tumorigenesis. PML nuclear bodies are disrupted in APL and in other more common malignancies. PML undergoes several post-translational modifications. We are currently studying how specific phosphorylation events control PML function. For example, we found that PML is aberrantly ubiquitinated upon a direct phosphorylation event mediated by the CK2 protein kinase. This event leads to disruption of the nuclear bodies and loss of PML mediated tumor suppression.
Cancer Biology, mouse models translational studies:
We study malignancies of the lung and of the hemopoietic system, using genetic and genomic approaches to uncover important genetic alterations that drive tumor initiation and progression. We are focusing our efforts on the study of oncogenic RAS induced non-small cell lung cancer and on the characterization of the function of the CK2 protein kinase in tumorigenesis. Approaches include tetracycline inducible and Cre/Lox-based conditional genetic systems to generate faithful murine models permitting study of the underlying biology of these tumors. To complement these studies, we are performing preclinical studies with small molecules that inhibit these signaling pathways and on banked human tumor specimens useful to detect genetic changes or other molecular signatures that can be correlated with clinical behavior and outcome.
RECENT PUBLICATIONS
P.P. Scaglioni and P.p. Pandolfi, "Taking apart a cancer protein" Nature, 426:512-13, 2003
R. Bernardi, P.P. Scaglioni, S. Bergmann, H.F. Horn, K.H. Vousden and P.P Pandolfi, "PML regulates p53 stability by sequestering Mdm2 to the nucleolus" Nature Cell Biology, 6:665-672, 2004
H. Matsushita, P.P. Scaglioni, M. Bhaumik, E.M. Rego, L.F. Cai, Hayato Miyachi, A. Kakizuka, W.H. Miller, P.P. Pandolfi, "In vivo analysis of the role of aberrant histone deacetylase recruitment and RARalpha blocade in the pathogenesis of acute promyelocytic leukemia" J Exp Med, 17:821-828, 2006
L.C. Trotman, A. Alimonti, P.P. Scaglioni, J.A. Koutcher, C. Cordon-cardo, P.P. Pandolfi, "Identification of a tumor suppressor network opposing nuclear Akt function" Nature, 25:523-527, 2006
P.P. Scaglioni, T. Yung, L. F. Cai, H. Erdjument-Bromage, P. Tempst, J. Teruya-Feldstein, P.P. Pandolfi, "A CK2-dependent pathway for PML degradation upon cellular and oncogenic stress" Cell, 126:269-83, 2006
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