Gallie, Brenda, M.D.

Professor, University of Toronto

Head Cancer Informatics

Ontario Cancer Institute/Princess Margaret Hospital

University Health Network

gallie@attglobal.net

   

Retinoblastoma is a rare childhood cancer that has been a prototype for recognition of the importance of genetic mutation in the initiation and progression of cancer. Mutations in the RB1 gene that cause these retinal tumors in children were first characterized in our lab 1988. A highly sensitive and cost effective methodology for identification of RB mutations was developed as a result of my clinical research at HSC, the Vision Research Center at TWH, and Visible Genetics, Inc, a successful startup company out of the Vision Research Center. Our detailed cost analysis indicates that molecular diagnosis is a superior approach with a beneficial impact on health care quality and economy. At OCI/PMH we investigate the basic mechanism by which inactivation of the RB1 leads to cancer of the retina. To learn about the mechanisms of cell proliferation and death in retinal development we have developed retinal explant culture system. At the Vision Research Center at TWH I collaborate with R. Bremner to understand the functions of the RB1 Protein. About 10% of all RB1 mutations are associated with fewer than usual number of retinoblastoma tumors in the persons with the RB1 mutations in their germline cells. These proteins are partially functional which we will use for correlation of the role of specific domains of RB1 proteins with biological function. Our studies defined the major mechanism of multidrug resistance in retinoblastoma tumors. This knowledge formed the basis of a modification of chemotherapy, which has resulted in best -yet success to save eyes with retinoblastoma. We have now designed a world-wide randomized trial to rigorously test the components of this protocol.

 
 

 

Technicians Clarellen Spencer Julie Anderson Suzanne Richter

Research Associate Sanja Pajovic

Graduate Students Vivette Brown Daved DiCuommo

Post Doctoral Fellows Christine Campbell Danian Chan

 
 

 

Gallie B. L., Campbell C., Devlin H., Duckett A. and Squire J. A. "Developmental basis of retinal-specific induction of cancer by RB mutation. Cancer Res. April 1999,1; 1731-1735.

Vivette D. Brown, Robert A. Phillips and Brenda L. Gallie, "Cumulative Effect of Phosphorylation of pRB on Regulation of E2F Activity." Mol.Cell. Biol. Vol.19, No.5 May 1999 p. 3246-3256.

Zacksenhaus E., Jiang Z., Hei Y.J., Phillips R.A. and Gallie B.L. "Nuclear localization conferred by the pocket domain of the retinoblastoma gene product." Biochim. Biophys. Acta September 1999. P288-296.