Our research program has taken advantage of multiple, complementary approaches, each aimed at understanding the mechanisms underlying progression through the mammalian cell cycle. In particular, we have chosen to focus on transcriptional mechanisms that link gene expression with cell cycle progression.
These studies have largely centered on the retinoblastoma tumor suppressor protein, pRB, and the related proteins p107 and p130. pRB is a prototypical tumor suppressor known to be mutated in many human tumors. pRB and its relatives restrain cell growth by inhibiting the activity of a cellular transcription factor, E2F, that controls the expression of key components of the cell cycle and DNA replication machinery. Using a combination of biochemistry, cell biology, and mutant cell lines, we are attempting to understand how critical gene targets are regulated by E2F and pRB. We have combined the use of a technique known as chromatin immunoprecipitation (ChIP) with a genomic approach employing DNA microarray analysis in order to begin understanding how gene regulatory networks are controlled during the cell cycle and differentiation in living mammalian cells. The pRB family controls a number of developmental decisions as well as cell cycle arrest in response to DNA damage. We hope to uncover novel targets of pRB that reveal a regulatory pathway of biologically relevant, functional interactions that drive cells toward each of these fates.
In addition to studies aimed at addressing transcriptional control of the cell cycle, we are also focusing on understanding another event linked to the cell cycle, namely duplication of centrosomes. The centrosome, involved in organizing the mitotic spindle, is poorly understood, although it was first observed 100 years ago. We have identified a novel protein, CP110, that may link the duplication of this organelle to the cell cycle. Since genomic instability ensues when CP110 is mutated, we are investigating potential links between this protein and human cancer.
Supplementary figures for Balciunaite et. al., MCB, 2005.
Professor, Department of Pathology
Scientific Director -Genomics Facility
PhD from University of California at Berkeley
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