Gregory Vanden Heuvel, PhD

Associate Professor
Department of Anatomy and Cell Biology

Ph.D.: 1994, University of Alabama at Birmingham
Postdoctoral: Yale University School of Medicine

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.

Recent Publications

1. Ledford AW, Kemeny G, Foreman T, Quaggin SE, Igarashi P, Oberhaus SM, Rodova M,
   Calvet JP, and Vanden Heuvel GB. Deregulated expression of the homeobox gene Cux-1 in
   transgenic mice results in down regulation of p27kip1 expression during nephrogenesis,
   glomerular abnormalities, and multiorgan hyperplasia. Developmental Biology, 245:157-171,
   2002.
2. Goyal S, Vanden Heuvel GB, and Aronson P. Renal Expression of Novel Na+-H+ Exchanger
   Isoform NHE8. Am. J. Physiol., 284:F467-73, 2003.
3. Brantley JG, Sharma M, Alcalay NI, and Vanden Heuvel GB. Cux-1 Transgenic Mice Develop Glomerulosclerosis and Interstitial Fibrosis. Kidney International, 63: 1240-1248, 2003
4. Iulianella A, Vanden Heuvel G, and Trainor P. Dynamic Expression of Murine Cux2 in
   Craniofacial, Limb, Neuronal, and Urogenital Primordia. Mechanisms of Development: Gene Expression Patterns 3: 571-577, 2003.
5. Sharma M, Fopma A, Brantley JG, and Vanden Heuvel GB. Coexpression of Cux-1 and
   Notch Pathway Components during Kidney Development, Developmental Dynamics 231:828
   838, 2004.
6. Sharma M, Brantley JG, Alcaley NI, Zhou J, Heystek E, Maser R, and Vanden Heuvel GB. Differential Expression of Cux-1 and p21 in Polycystic Kidneys from Pkd1 Null and cpk Mice, Kidney International, 67:432-442, 2005.
7. Vanden Heuvel GB, Brantley JG, Alcalay NI, Sharma M, Kemeny G, Warolin J, Ledford AW, and Pinson DM. Hepatomegaly in Transgenic Mice Expressing the Homeobox Gene Cux-1, Molecular Carcinogenesis, 43:18-30, 2005.
8. Vanden Heuvel GB, Payne JA, Igarashi P, and Forbush B 3rd. Expression of the
   basolateral Na-K-Cl cotransporter during mouse nephrogenesis and embryonic development. Gene Expr Patterns, 2:1000-1006, 2006.
9. Alcalay NI, Brantley JG, Sharma M, Gooch J, and Vanden Heuvel GB. Ectopic Expression
   of the Homeobox Gene Cux-1 Rescues Metanephric Growth Inhibition by Cyclosporin A, Developmental Dynamics 236:184-191, 2007.
10. Iulianella A, Sharma M, Durnin M, Vanden Heuvel GB, and Trainor P. Cutl2
    (Cux2) regulates neural precursor proliferation and differentiation in the developing spinal cord,
    Development, 135:729-741, 2008
11. Alcalay NI, and Vanden Heuvel GB. Pathophysiological roles of Cux1: Regulation of cell proliferation and differentiation in the kidney, Frontiers in Bioscience, in press.