Research Interests

Kidneys from kinesin-II deficient mice (left) and wild-type mice (right). The mutant kidney is enlarged due to polycystic kidney disease.

Our laboratory studies kidney development, molecular genetics, and polycystic kidney disease. One goal of our research is to understand the transcriptional regulation of kidney development and kidney-specific gene expression. Current studies are focused on the transcription factors Pod-1 and HNF-1ß. Pod-1 is a basic-helix-loop-helix protein that is expressed in the developing kidney. Studies using knockout mice have shown that Pod-1 is essential for the differentiation of podocytes (glomerular visceral epithelial cells), which are the cells that are responsible for generating and maintaining the glomerular filtration barrier. We are using a biochemical approach to identify the proteins that interact with Pod-1 and the genes that it regulates. These studies are important for understanding how the glomerulus develops and how proteinuria arises in diseases such as diabetes mellitus. HNF-1ß (hepatocyte nuclear factor 1ß) is a homeodomain protein that regulates tissue-specific gene expression. Humans with autosomal dominant mutations of HNF-1ß develop renal abnormalities including renal cysts, cystic dysplasia, and glomerulocystic disease. We have recently shown that the renal abnormalities arise in part from down-regulation of the autosomal recessive polycystic kidney disease gene, PKHD1. Current studies are directed at further elucidating how mutations of HNF-1ß produce renal disease in mice and humans.

A second goal of our research is to understand the pathogenesis of polycystic kidney disease (PKD). PKD is the most common genetic cause of renal failure in humans and is characterized by the accumulation of fluid-filled cysts in the kidneys and other organs. Recent studies suggest that PKD may arise from abnormalities of the primary cilium, a hair-like organelle that projects from the cell surface. Using a genetic method called Cre/loxP recombination, we have produced transgenic mice that are deficient in kinesin-II, a motor protein that is required for cilia synthesis. Kinesin-II-deficient mice lack renal cilia and develop PKD. Current studies are directed at understanding how the loss of renal cilia produces kidney cysts. We are also using Cre/loxP recombination to create additional animal models that can be used to study the pathogenesis and treatment of PKD.


Lin F, Hiesberger T, Cordes K, Sinclair AM, Goldstein LS, Somlo S, Igarashi P. Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5286-91.

Lin F, Cordes K, Li L, Hood L, Couser WG, Shankland SJ, Igarashi P. Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol. 2003 May;14(5):1188-99.

Bai Y, Pontoglio M, Hiesberger T, Sinclair AM, Igarashi P. Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear factor-1beta. Am J Physiol Renal Physiol. 2002 Oct;283(4):F839-51.

Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2002 Sep;13(9):2384-98.

Shao X, Somlo S, Igarashi P. Epithelial-Specific Cre/lox Recombination in the Developing Kidney and Genitourinary Tract. J Am Soc Nephrol. 2002 Jul;13(7):1837-46.

Shao X, Johnson JE, Richardson JA, Hiesberger T, Igarashi P. A minimal ksp-cadherin promoter linked to a green fluorescent protein reporter gene exhibits tissue-specific expression in the developing kidney and genitourinary tract. J Am Soc Nephrol. 2002 Jul;13(7):1824-36.

Ledford AW, Brantley JG, Kemeny G, Foreman TL, Quaggin SE, Igarashi P, Oberhaus SM, Rodova M, Calvet JP, Vanden Heuvel GB. Deregulated expression of the homeobox gene Cux-1 in transgenic mice results in downregulation of p27(kip1) expression during nephrogenesis, glomerular abnormalities, and multiorgan hyperplasia. Dev Biol. 2002 May 1;245(1):157-71.