The University of Alabama at Birmingham (UAB) Recessive Polycystic Kidney Disease Core Center (UAB RPKDCC) was originally established as a UAB-based interdisciplinary center of excellence in PKD-related research, with specific emphasis on recessive PKD. The Core Center was supported by an award from the NIDDK (P30 DK074038).
As we developed the competitive renewal of our Core Center, recent advances in the field prompted us to re-evaluate our focus. Specifically, we note: 1) the burgeoning data that implicate ciliary dysfunction as central mechanism in renal cystogenesis among a phenotypically diverse set of recessive disorders; 2) the mutational data that demonstrate defects in a single gene can result in a spectrum of disease phenotypes; and 3) the common signaling pathways that are implicated in disease pathobiology. Therefore, we have broadened the scope of our Core Center to focus on the hepato/renal fibrocystic diseases. Accordingly, we have renamed the Center, the UAB Hepato/Renal Fibrocystic Diseases Core Center (UAB HRFDCC).
The UAB HRFDCC builds on our previous P30-funded, UAB-based interdisciplinary center of excellence in PKD-related research, and expands the emphasis to include single-gene disorders encompassed in the hepato/renal fibrocystic diseases spectrum. Our objectives will be implemented in three specific aims:
Aim 1: To facilitate hypothesis driven-research through the support of shared Core facilities and to leverage these core technologies into new projects, interactions, and collaborations in PKD-related research, with emphasis on the hepato/renal fibrocystic diseases spectrum of disorders.
Aim 2: To foster meaningful interactions among UAB and MUSC Core Center investigators and extend these interactions to include a cadre of investigators from multiple institutions across the US and Canada – an extended research base.
Aim 3: To provide, through the Biomedical Research Cores, the Pilot and Feasibility Program and the Educational Enrichment Program, the intellectual resources and the research infrastructure to attract new and established investigators to PKD-related research.
B. Thematic Organization of the UAB HRFDCC
The hepato/renal fibrocystic diseases appear to result from partial or complete loss of cystoprotein function. A major consequence of these protein defects is the structural/functional impairment of the primary apical cilium, a central effector in disease pathogenesis. Therefore, this Core Center is organized around four interrelated thematic areas:
- Cilia-related biology, including calcium -mediated mechanotransduction pathways
- Regulation of epithelial transport pathways
- Signaling pathways critical in development and epithelial differentiation
- Matrix biology and fibrosis.
These areas of emphasis incorporate the major mechanistic pathways implicated in the pathogenesis of recessive PKD. The main objective of this Core Center is to apply scientifically rigorous, state-of-the-art methodologies in a cost-effective manner to address experimental questions in these thematic areas that will 1) advance understanding of disease pathogenesis, 2) enhance diagnostic specificity, and 3) expand therapeutic approaches in patients with hepato/renal fibrocystic diseases, particularly those with autosomal recessive polycystic kidney disease (ARPKD).