Core A: Hepato-Renal Fibrocystic Disease Translational Resource

Director: Lisa M. Guay-Woodford, MD; lguaywoo@childrensnational.org (202) 476-6439
Co-Director: William E. Grizzle, MD, PhD; wgrizzle@uab.edu (205) 934-4214

The UAB Core Center initially focused on supporting researchers who are investigating biological themes relevant to clinical disease progression and the molecular pathogenesis of autosomal recessive polycystic kidney disease (ARPKD). However, studies in the last several years have demonstrated that ARPKD and other single gene disorders characterized by renal cystic disease and extra-renal phenotypes share numerous pathogenic features and involve proteins that are critical in the structure/function of the primary apical cilium. As a result, this very broad class of disorders is increasingly referred to the "ciliopathies". A subset of the ciliopathies is specifically characterized by fibrocystic disease of the kidney and dysgenesis of the porto-biliary tract (congenital hepatic fibrosis and/or Caroli disease), prompting a redefinition of these disorders as hepato-renal fibrocystic diseases.

While ARPKD is considered to be the flagship disorder in this new sub-classification, autosomal dominant polycystic kidney disease (ADPKD) can be associated with congenital hepatic fibrosis and/or Caroli disease and rarer recessive disorders such as nephronophthisis, Joubert syndrome, Bardet Biedl syndrome, Meckel-Gruber syndrome, and oro-facial-digital syndrome, which all have variable degrees of renal and/or biliary involvement. Therefore, our Core Center has expanded its scope and will support a broader range of research activities that focus on the hepato/renal fibrocystic diseases.

The Core has three primary objectives:

Aim 1: Expand the Clinical Database established to include patients with ARPKD and other hepato-renal fibrocystic diseases.

Aim 2: Establish a national tissue repository for hepato-renal fibrocystic diseases.

Aim 3: Broaden the portfolio of educational information and tools to encompass the hepato-renal fibrocystic disease spectrum of disorders, particularly ARPKD.

A unique aspect of this Core is that it builds on established clinical, genotyping, and educational programs. Through the P30 mechanism, Core A will make these important resources available to the broader community of interested investigators, affected patients and families, and physicians/healthcare providers.