Principal Investigator: Hui Shen, Ph.D., PI
Postdoc Research Fellow: Lijun Tan, Ph.D.,
Research Assistant: Chuan Qiu
Epigenetics is the new paradigm on the horizon for basic and translational research for complex diseases including osteoporosis. Epigenetic factors refer to reversible, heritable changes in gene regulation that occur without a change in DNA sequences. Two of the most extensively investigated epigenetic factors are DNA methylation and histone modifications. Other epigenetic mechanisms include regulation by non-coding RNAs, such as microRNAs, and mechanisms that control the higher-level organization of chromatin within the nucleus. The constitution of epigenetic marks at a locus for a given time point and cell type forms the epigenotype. Because genomic DNA must exist in a particular chromatin configuration, the genotype can only give rise to phenotype through the prism of the epigenotype, making it an excellent candidate to modify the effects of the genotype and play a role in mediating penetrance and variation in expression.
The epigenotype shows far greater plasticity than the genotype in the normal development of an individual, and it is reasonable to speculate that epigenetic errors could be a major
contributor to human diseases. Emerging evidence suggests that dysregulation of epigenetic factors is an important regulatory and heritable mechanisms in the pathophysiology of human complex diseases, especially for common late-onset disorders. Moreover, given the reversible and relatively easily modifiable nature of epigenetic changes, understanding and manipulating the epigenetic mechanisms hold enormous imminent promise to significantly improve the intervention and treatment of human complex diseases.
A number of molecular epigenetic studies have suggested that epigenetic factors play significant roles in osteogenic cell differentiation and bone metabolism. However, the comprehensive role of epigenetic factors in the pathophysiology of osteoporosis in humans is largely unknown at this time. Such knowledge is necessary and essential in order to identify additional and novel heritable factors contributing to BMD variation and osteoporosis risks, and holds great potential to cross-link basic and clinical research.
We have recently initiated research projects to comprehensively investigate potential epigenetic changes associated with risk to osteoporosis, using state-of-the-art technologies, such as MeDIP-seq and ChIP-seq. These projects are focused on three major epigenetic mechanisms (DNA methylation, histone modification, and microRNA expression), respectively, at the whole epigenome level.