Jordan Kreidberg

Department of Pediatrics
Children's Hospital
300 Longwood Ave.
Boston, MA 02115
Tel: (617) 919-2959
Fax: (617) 730-0129
Email: Jordan.kreidberg@childrens.harvard.edu
12 postdoctoral fellows

Our research focuses on how stem cell and progenitor populations in developing organs are regulated by signaling networks. Important areas of study include how integrin cell adhesion receptors and receptor tyrosine kinases integrate signals that control the gene expression of signaling molecules that regulate stem cell populations and that also regulate morphogenetic events during organogenesis. We are also studying how transcription factors and chromatin modification proteins are involved in organ development.

Recently, we determined that angioblasts, the precursors of endothelial cells in the vascular system, are involved in the early inductive events of the kidney. We are presently attempting to identify the angioblast-derived signals and are also studying whether signals derived from these angioblasts are targeted to stem cell populations. It is also being determined whether stem-cell associated genes, such as Nanog and members of the Polycomb Group, whose expression we have defined in the developing kidney, are targets of the angioblast signals, or other signals known to be important in the induction of the kidney.

As part of our studies on organ development, a major focus has been the Wilms’ tumor-1 tumor suppressor gene, that encodes a zinc finger transcription factor. Knockout of this gene completely blocks kidney and gonad development. We are using approaches that include in vitro and in vivo RNAi, conditional gene knockout, and microarrays to identify Wt1 target genes within the stem cell population of the kidney. The Wilms’ Tumor gene is also expressed in podocytes, a key cell type in the kidney, that is damaged in chronic renal failure, and our efforts include the understanding of how this gene is involved in kidney disease.

References:

• Gao X, Chen X, Taglienti M, Rumballe B, Little MH, Kreidberg JA. Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa. Development. 2005 Dec;132(24):5437-49.
• Chattopadhyay, N.,Wang, Z. Ashman, L.K., Brady-Kalnay, S.M., Kreidberg, J.A. a3b1 integrin:CD151, a component of the cadherin:catenin complex, regulates PTPm expression and cell-cell adhesion. 2003 Journal of Cell Biology, 163:1351-1362.
• Natoli, T.A., Alberta, J.A., Bortvin, A., Taglienti, M., Menke, D., Loring, J., Jaenisch, R., Page, D., Housman, D.E., and Kreidberg, J.A. WT1 is required cell-autonomously for the development of all gonadal cell lineages, including the germ cell to gonocyte transition. Developmental Biology 268:429-40.