Human genomic DNA is the ultimate blueprint of our heredity. The genetic information of the human genome holds the key to the most fundamental questions in human biology of health and disease. However, understanding of gene regulation that is governed by information not only encoded in the DNA sequence but also environmental factors – the essence of epigenetics – requires innovative approaches to genomic sciences. Our research being carried out with multifaceted and integrative approaches aims to address the biology of epigenetic control of the human genome to attain both mechanistic insights and rational design of small-molecule probes that modulate functions of chromosomal proteins. The emphasis is on the role of chemical modifications of chromatin in regulation of gene transcription. Towards this end, we are developing an interdisciplinary genomics research paradigm to conduct genome-wide functional profiling of chromatin-associated proteins in epigenetic gene regulation – an emerging field that we term Structural and Chemical Epigenomics. This paradigm relies on integrated structural and chemical biology, and molecular/cellular chromatin biology. To understand epigenetic gene regulation at the fundamental molecular level, we simultaneously conduct interdependent research in:
- Family-wide functional profiling of proteins in chromatin modifications and molecular interactions.
- Structure-based rational design of small-molecule chemical probes for chromosomal proteins.
- Chemical epigenomics study of histone-directed chromatin biology in health and disease. Our research in structural and chemical epigenomics, as we expect, has broad implications in human biology of health and disease, ranging from cell development, to stem cell self-renewal and differentiation, and re-programming to human diseases including cancer, inflammation, and neurodegenerative disorders.