Stephen X. Skapek, M.D.

Comer Children's Hospital Chicago
Functional and Genetic Analysis of a Novel RB-Associated Transcriptional Repressor in Human Leukemia and Lymphoma

Researchers have identified and studied a gene known as the RB gene that acts as a natural tumor suppressor by regulating cell proliferation (multiplication of cells). Abnormal cell proliferation is one characteristic of cancer, and the inability to "turn off" inappropriate proliferation may be a key step in the formation of some cancers. Research has not yet identified precisely how RB influences cell proliferation; however, there is evidence that other substances interact with RB to regulate its function and help it control cell proliferation. Substances known as transcriptional repressors may interact with RB and help regulate cell proliferation by interfering with transcription, the process by which a gene's DNA is copied to RNA. Until recently, the idea that transcriptional repressors interact with RB was purely theoretical-no specific transcriptional repressors that interact with RB had been identified. However, Dr. Skapek at St. Jude Children's Research Hospital in Memphis, Tennessee has cloned a novel gene that codes for a transcriptional repressor, RBaK, that interacts with RB. In vitro tests suggest that RBaK and RB together cooperate to regulate cell proliferation. By studying the mechanisms by which RB functions as a tumor suppressor, specifically with regard to RBaK, Dr. Skapek hopes to shed light on the molecular mechanisms by which RB functions. This may potentially lead to new therapeutic strategies in which RBaK itself could be manipulated. To accomplish this, Dr. Skapek intends to pursue two avenues of research simultaneously. One line of research will examine how RBaK and RB interact to regulate cellular proliferation. The other will evaluate the importance of RBaK in hematologic malignancies by attempting to locate the gene that codes for RBaK on human chromosomes, and examining leukemia/lymphoma samples and tumor-derived cell lines for evidence of abnormalities in this gene.