Julien Sage

Research/Lab website:   Personal Web site

The accumulation of alterations can transform a normal cell into tumor cells. Despite the vast amount of knowledge gained in the last 30 years, cancer is now the first cause of death in the United States. Some key aspects of current basic cancer research include deciphering the molecular circuits controlling cellular proliferation, understanding and detecting the earlier stages of tumor development, and comprehending the interactions between tumor cells and their host.

Our research focuses on the retinoblastoma tumor suppressor gene (RB). RB is found mutated in a broad range of human tumors, including familial retinoblastoma and carcinomas of the lung, breast, liver, bladder, and prostate. RB normally works as a negative regulator of cell division, and RB mutation leads to uncontrolled proliferation. Our goal is to take advantage of the central role of RB in cell cycle control and tumorigenesis in order to address basic issues in cancer.

One part of our work is to develop mouse models of human cancers associated with loss of RB function. Using these models, we aim to identify the cell of origin of cancer and the order of mutations involved in cancer progression. Tumors in mice resemble human tumors in many ways, and design and testing of new therapeutic strategies in mouse models of human cancers will speed anti-cancer therapies.

In parallel to our studies in vivo using genetically engineered mice, we take advantage of RNA interference strategies to characterize the mode of action of Rb family members in human primary cells.

RB is a prototypic tumor suppressor gene. The complex functional interactions between RB family members illustrate the complexity of signaling networks in mammalian cells. A better understanding of the RB family will allow for a better understanding of key events in tumorigenesis and organismal development.