Cores

This P30 Core Center includes four Biomedical Research Cores that integrate existing intellectual and technological resources at UAB and MUSC to provide a set of services/resources that will enable innovative investigations in the four thematic areas. The proposed biomedical cores are: 1) Core A: The Hepato/Renal Fibrocystic Disease Translational Resource; 2) Core B: The Engineered Models Resource; 3) Core C: The Cellular Physiology Resource; 4) Core D: The Immunoreagent and Structural Characterization Resource. A brief introduction to each of these Cores is provided below.

Core A: The Hepato/Renal Fibrocystic Disease Translational Resource

Director: Lisa M. Guay-Woodford, MD
Co-Directors:
Gary R. Cutter, PhD (Head, Research Methods and Clinical Trials; UAB Department of Biostatistics)
William E. Grizzle, MD, PhD (Director, Tissue Procurement Service; UAB Comprehensive Cancer Center)
Ludwine Messiaen, PhD (Director, UAB Medical Genomics Laboratory)

The objectives of this Core are:

  1. to establish a national Tissue Repository for hepato/renal fibrocystic diseases;
  2. to expand the clinical and mutational database established in our current P30-funded Core Center and develop a companion DNA Repository; and
  3. to broaden the portfolio of educational tools developed for physicians and patients to encompass the natural history, pathogenesis, and genetic testing opportunities in 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 and through the P30 mechanism will make these data/resources available to the broader community of interested investigators.


Core B: The Engineered Models Resource

Director: Bradley K. Yoder,  PhD
Co-Director: Robert Kesterson, PhD (Director, UAB ES Cell/Transgenic Core Facility) 

The objective of this Core is to provide investigators with novel model systems for in vivo functional analysis of cystic kidney disease genes (cystogenes). The Core has three aims:

  1. to generate and provide mouse models and related resources derived from these models for the analysis of cystic kidney disease pathogenesis;
  2. to generate Cre-inducible expression systems for in vivo analysis of gene function and assessment of the pathogenic potential of missense mutations; and
  3. to facilitate the use of C. elegans for analysis of cystoprotein localization, interactions and function.

The mouse models generated in this core will also provide important resources for the isolation of constitutive mutant or inducible mutant cell lines/tubules for subsequent in vitro analyses performed by Core C: The Cellular Physiology Resource. Core B has already assembled a wide range of mouse and C. elegans lines with mutations in genes involved in ciliogenesis, MKS, NPHP, and BBS. These lines will provide a unique resource for UAB HRFDCC investigators to explore interactions between disease pathways involved in diverse forms of cilia-related hepato/renal fibrocystic diseases.


Core C: The Cellular Physiology Resource

Director: P. Darwin Bell, PhD
Co-Director: Wayne R. Fitzgibbon, PhD 

This Core will provide a comprehensive facility to develop cell line resources and perform state-of-the-art physiological experiments in cells and tissues derived from mouse models of the hepato/renal fibrocystic disease spectrum of disorders. The Core has three aims:

  1. to provide mTERT immortalized cell lines and serve as a repository for established cell lines from kidney, liver or other cystic disease-related organs;
  2. to characterize reagents and cell lines developed in other UAB HRFDCC Cores, as well as by the internal and external user base. To perform state-of-the-art physiological measurements in cell culture models grown on permeable supports – e.g. to evaluate water and ion transport pathways through measurements of membrane potentials, short circuit currents, and transepithelial voltages and to measure intracellular and subcellular concentrations of calcium, pH, and sodium;
  3. to use an in vivo adult mouse model of reduced renal mass to assess the initiation and progression of cystogenesis in mice with conditional floxed alleles to knockout cystoproteins. This will involve longitudinal MRI studies, histological analysis, and measurements of GFR and renal blood flow.

One unique aspect of this Core is the breadth of experimental tools and resources that have been amassed to attack specific problems and questions. Other unique aspects of this Core are the ability to use freshly isolated tissues, produce primary and immortalized cell lines, and develop experimental procedures and techniques that maximize the physiological information that can be obtained.


Core D: The Immunoreagent and Structural Characterization Resource

Director:  Kent Keyser, PhD (Director, UAB High Resolution Imaging Facility)
Co-Directors:
Mary Ann Accavitti-Loper, PhD (Director, UAB Epitope Recognition and Immunoreagent Core)
Gene P. Siegal, MD, PhD (Director, UAB Division of Anatomic Pathology)

Analysis of human and genetically-engineered mouse models requires thorough morphological examination of tissues from affected individuals. The objective of this Core is to provide P30 investigators with access to sophisticated, state-of-the-art technology for the detection and characterization of morphological changes associated with the hepato/renal fibrocystic disease spectrum of disorders. The Core has three aims:

  1. to develop, test, and distribute novel immunoreagents through a highly experienced, state-of-the-art resource;
  2. to provide processing and data accumulation of experimental model tissues using specialized techniques including gross and microscopic morphology, morphometry, in situ hybridization, immunohistochemistry, and laser capture microdissection (LCM); and
  3. to provide consultation in the design and conduct of electron microscopy (EM), confocal and multiphoton imaging, and Stimulated Emission Depletion (STED) microscopy experiments.

The core will have extensive interactions with Engineered Models Core (Core B) to characterize phenotypes associated with the models being established and for generation of novel immunoreagents to ciliary-cystoproteins.