Faculty

Research Description

The controlled expression of genes during development is of fundamental importance in the differentiation of eukaryotic cells. My research concerns the molecular basis of cellular differentiation using the developing kidney as a model. We are, in particular, interested in the role of a novel homeobox gene, called Cux-1, which functions as a transcriptional repressor of genes specifying terminal differentiation in multiple cell lineages. In the kidney, Cux-1 is expressed in the early developmental stages, but is sharply down regulated when cells undergo terminal differentiation. Previous studies from my laboratory demonstrate that preventing the normal down regulation of Cux-1 in transgenic mice results in abnormal cell proliferation. We have determined that Cux-1 regulates the cell cycle during kidney development by repressing the gene encoding the cyclin kinase inhibitor, p27. Moreover, we have found that the ectopic expression of Cux-1results in glomerulosclerosis. Additional studies from my laboratory have shown that Cux-1 is ectopically expressed in two different mouse models of polycystic kidney disease. Recent studies from my laboratory have revealed that Cux-1 is upregulated by Notch-1 and interacts with the corepressor TLE-4, suggesting that Cux-1 is an effector of the Notch signaling pathway. Our current studies are directed at identifying the molecular mechanism by which Cux-1 regulates p27 expression, and determining the role of Cux-1 in polycystic kidney disease. 

We are also interested in the role of Cux-1 in spermatogenesis.  A truncated Cux-1 protein, called Testis Cux-1, is expressed in round spermatids.  Round spermatids are post-meiotic, suggesting that Cux-1 plays a role unrelated to cell cycle regulation during spermatogenesis.  Current studies are directed at deciphering the role of Cux-1 in round spermatids.