Education
Postdoc, Yale University School of Medicine, Developmental Nephrology
Ph.D., University of Alabama at Birmingham, 1994
M.S., Western Michigan University, 1988
B.S., Grand Valley State College, 1984
Calvin College
Dordt College
Courses Taught
- BIOL 241 College Biology I
- BIOL 364 Microbiology and Immunology Labs
- BIOL 321 Human Physiology
- BIOL 321 Human Physiology Labs
Membership in Professional Societies
- American Society for Cell Biology
- American Society of Nephrology
- American Physiological Society
- Society for Developmental Biology
Research
The controlled expression of genes during development is of fundamental importance in the differentiation of eukaryotic cells. My research is directed at understanding 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 Cux1, which functions as a transcriptional repressor of genes specifying terminal differentiation in multiple cell lineages. In the kidney, Cux1 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 Cux1 in transgenic mice results in abnormal cell proliferation. We have determined that Cux1 regulates the cell cycle during kidney development by repressing the gene encoding the cyclin kinase inhibitor, p27. Additional studies from my laboratory have shown that Cux1 is abnormally expressed in polycystic kidney disease. Our current studies are directed at identifying the molecular mechanism by which Cux1 regulates p27 expression, and determining the role of Cux1 in polycystic kidney disease.
Recent Publications
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.
Goyal S, Vanden Heuvel GB, and Aronson P. Renal Expression of Novel Na+-H+ Exchanger Isoform NHE8. Am. J. Physiol., 284:F467-73, 2003.
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.
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.
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. *undergraduate author
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. *undergraduate author
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. *undergraduate author
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.
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.
Iulianella A, Rey JP, Durnin M, Sharma M, Vanden Heuvel GB, and Trainor P. Cutl2 (Cux-2) regulates neural precursor proliferation and differentiation in the developing spinal cord, Development 135:729-741, 2008.
Alcalay NI, Sharma M, Vassmer D, Chapman B*, Paul B, Zhou J, Brantley JG, Wallace DP, Maser RL, and Vanden Heuvel GB. Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux-1, Am. J. Physiol. Renal 295:F1725-F1734, 2008. *undergraduate author
Sharma M, Brantley JG, Vassmer D, Baas J*, and Vanden Heuvel GB. The homeodomain protein Cux1 interacts with Grg4 to repress p27kip1 expression during kidney development, Gene, 439:87-94, 2009. *undergraduate author
Iulianella A, Sharma M, Vanden Heuvel GB, and Trainor PA. Cux2 functions downstream of Notch signaling to regulate dorsal interneuron formation in the spinal cord, Development, 136:2329-2334, 2009.
Alcalay NI, and Vanden Heuvel GB. Regulation of cell proliferation and differentiation in the kidney. Invited review for Frontiers in Bioscience 14:4978-4991, 2009.
Vanden Heuvel GB. CD14 : a candidate biomarker for the prognosis of polycystic kidney disease. Kidney International 78:537-538, 2010.
Sharma M, Callen S, Zhang D, Singhal PC, Vanden Heuvel GB, and Buch S. Activation of the Notch Signaling Pathway in Human Immunodeficiency Virus Associated Nephropathy, AIDS, 24:2161-2170, 2010.
Kroll MR*, Viss ES*, Lamb J, Horstman J*, Powell A*, Van Wyk A*, Hinkkala K*, Taylor A*, Schippers M*, Shannon S*, Carlton CG, Sharma M, Vanden Heuvel GB, and Jelsma TN. Asynchronous Expression of the Homeodomain Protein Cux1 in Sertoli Cells and Spermatids during Spermatogenesis, Biology of Reproduction, 84:455-465, 2011. (COVER PHOTO) *undergraduate author
Paul BM, Vassmer D, Taylor A*, Magenheimer L, Carlton CG, Piontek KB, Germino GG, and Vanden Heuvel GB. Cux1 is associated with apoptosis during late stage cyst progression in the cpk and Pkd1CD mouse models of PKD, Developmental Dynamics, 240:1493-1501, 2011. *undergraduate author