Christopher Ward, M.B., Ch.B., Ph.D.
Kidney Institute - Faculty
Department of Internal Medicine, Division of Nephrology and Hypertension
Ph.D., University of Birmingham, UK
M.B., Ch.B., Edinburgh University
Christopher Ward, M.B., Ch.B., Ph.D., has a major research interest in autosomal dominant polycystic kidney disease (ADPKD), a disease in which the kidney (and to a lesser extent the liver) develops small fluid-filled cysts that gradually enlarge as the affected individual ages.
The cysts and associated fibrosis damage the kidney, causing it to fail in the fifth to sixth decade of life. The disease is genetically inherited, so an affected individual has a 50 percent chance of having an affected child.
Dr. Ward was involved in cloning the genes for one of the dominant forms of the disease - PKD1 - and the severe recessive form of the disease, PKHD1. His research involves understanding the mechanisms underlying the disease and developing tests and treatments for it.
Dr. Ward has four major focus areas:
- Developing animal models for ADPKD and ARPKD
- Studying the product of the PKD1 gene, polycystin-1, which he has shown to be abundant in small, membrane-bound vesicles (exosomes) that are shed into the urine
- Determining the identity of the proteins that interact with polycystin-1 in urinary exosomes
- Developing urine-based tests for polycystic kidney disease
Significance to patient care
Dr. Ward and his colleagues are using animal models of cystic disease to search for new drugs that make the disease less severe. Some of the drugs tested on their mouse and rat models are now undergoing clinical trials in PKD patients.
Dr. Ward also is working on urine-based tests that can be used to diagnose cystic disease before cysts are seen on scans, as well as monitor cystic disease and its response to treatment. He is actively studying how defects in the polycystin-1 protein cause cysts to develop in mice, rats and humans.
His team hopes that the drugs they find will slow cystic disease enough that individuals with this genetic disease do not go into renal failure and are spared dialysis or renal transplantation.
Figure 1 (PC1_LOV1.pdf): PC1 and LOV-1 are topologically similar with 11 TMs and conserved extra and intracellular loops. Both have a cytoplasmic C-terminal region and extensive extracellular N-terminal region. The two proteins have PLAT, and GPS domains, the latter are expected to be cleaved resulting in a N-terminal and C-terminal portions. The first extracellular region is composed of a mucin domain in LOV-1 and a mosaic of different domains in the PC1.
Figure 2 (PC2_LOV2.pdf): PC2 and PKD-2 (LOV-2) are have 36% similarity at a primary amino acid sequence level and are very similar at a topological level, both have C-terminal coiled coil domains which are predicted to be intracellular.