Anthony J. Capobianco, Ph.D.

Associate Professor
Molecular and Cellular Oncogenesis Program
215-495-6816, Office
acapobianco@wistar.org

Introduction

Cancer is a disease of cellular growth control gone awry. Cancerous cells arise as a result of the accumulation of genetic mutations that either activate cancer-causing genes or inactivate tumor-suppressing genes. The consequence of these mutations is the disruption of the normal controls that govern proliferation and differentiation. The laboratory of Anthony J. Capobianco, Ph.D., studies the molecular sequences of events set in motion by certain genetic mutations to better understand not only cancer processes but also normal and abnormal development

Research Summary

The elucidation of the molecular mechanisms that drive neoplastic transformation are of primary importance, not only to expand our conceptual knowledge of oncogenesis and signal transduction but also to provide direct insight into the complex processes of development. Research in the Capobianco lab is directed to understanding how proto-oncogenes exert their effects on cells and how, when oncogenically activated, they subvert normal cellular processes. The long term goal is to understand the complex circuitry that coordinates intricate cellular programs such as proliferation and differentiation. Presently, research is directed toward the elucidation of the Notch signaling pathway and how deregulation of this pathway leads to neoplasia. Notch proteins are members of an evolutionary conserved family of receptors. In mammalian development, Notch proteins appear to play an important role in the regulation of proliferation and cell-fate decisions during development. Consistent with this role, mutations in various members of the Notch signal transduction system leads to a number of human developmental disorders and cancer. However, it is unknown how mutations in these genes contribute to the development of these disorders at the molecular level. Projects in the lab include the biochemical dissection of the Notch signaling mechanism in neoplastic transformation, identification and characterization of genes involved in progression of leukemogenesis, and the elucidation of DSL (Notch-ligands) function in epithelial and lymphoid growth and differentiation.

Selected Publications

Beverly, L. and Capobianco, A.J. 2003. Perturbation of Ikaros Isoform selection by MLV integration is a cooperative event in Notch-induced Leukemogenesis. Cancer Cell 3(6) 551-564.

Ascano, J.M, Beverly, L.J., and Capobianco, A.J. The C-terminal PDZ-ligand of JAGGED1 is essential for cellular transformation. J. Biol. Chem. 2003 Mar 7;278(10):8771-9.

Jeffries, S., Robbins, D.J. and Capobianco, A.J. 2002. Characterization of a large Molecular Weight Complex in the Nucleus of Notchic-Transformed cells and in a human T-Cell Leukemia Cell Line. Mol. Cell. Biol. 2002. 22: 3927-3941

Ronchini, C. and Capobianco, A.J. 2001. Disruption of Cell Cycle Control in Notchic -Transformed Cells Through Direct Induction of Cyclin D1 Transcription. Mol. Cell. Biol. 21(17):5925-5934.

Jeffries, S. and Capobianco, A.J. 2000. Neoplastic Transformation by NOTCH Requires Nuclear Localization. Mol.Cell.Biol. 20(11):3928-3941

Ronchini, C. and Capobianco, A.J. 2000. Notchic-ER Chimeras Display Hormone-Dependent Transformation, Nuclear Translocation, Phosphorylation and CBF1 Activation.Oncogene. 2000 Aug 10;19(34):3914-24.