- Genetic analysis of intractable pediatric diseases
- Establishment of new mouse disease models
- New iPS cell disease models
- New medical treatments for cholestasis
- Study of bone development and growth in children
Development of new iPS cell models, genetic analysis methods and treatments for intractable pediatric diseases
Despite great advances in medical care, the still remains an extraordinary number of children who suffer from rare and intractable diseases. We are looking to develop new methods, beginning with genetic analysis, that will lead to effective therapies for these patients. For example, mucopolysaccharidoses is a pediatric metabolic disorder that is the result of dysfunctional lysosomal enzymes that fail to process polysaccharides. The disease comes in many types, each due to a gene mutation. We have conducted exosome analysis on patient samples to develop better diagnostic tools including the screening of genes not previously associated with the disease. Gene knockdown in cells revealed that a mutation in the VPS33A gene may contribute to the excess polysaccharides by lowering the lysome pH. Another genetic pediatric disease of interest, Acromesomelic dysplasia, Maroteaux type, causes dwarfism. The disease is caused by a loss-of-function mutation in NPRB. On the other hand, we discovered a gain-of-function mutation in the NPRB gene and that the CNP / NPRB pathway may promote cartilage growth. We are planning to prepare iPS cells from patients and combine them with genome editing to analyze the pathology of such diseases and develop new therapies.