Non-Coding Genome in Normal and Cancer Stem Cells
Advances in genome sequencing are poised for applications in personalized medicine. However, current understanding of disease-causing genetic alterations is largely based on protein-coding DNA sequences consisting of only ~1% of human genome. It remains unclear how alterations within non-coding genome, consisting of various regulatory elements and mobile DNA sequences, contribute to disease pathophysiology. Similarly, genotype-phenotype association studies continue to elucidate non-coding genomic regions that are altered in human diseases, although identification of causal elements remains challenging, impeding drug development and therapeutics.
We aim to develop experimental and computational methodologies, and integrate with in vitro and in vivo disease modeling toward a systems-level view of disease-associated non-coding genetic elements in development and diseases. This is possible by mapping genetic and epigenetic events that discriminate the normal and neoplastic genomes, coupling epigenetic changes with genetic lesions and gene expression programs, and conducting mechanistic studies of individual candidates in disease models.
By comparing the regulatory composition of gene regulatory networks in normal and neoplastic hematopoiesis, we aim to investigate how non-coding regulatory genome, lineage-specifying regulators, epigenetic modulators and environmental signals cooperate to control lineage specification, and how dysregulation of these mechanisms contributes to cancer development.
Ongoing studies in our lab include:
- Oncogenic cooperation between coding and non-coding variants in cancer pathophysiology
- Integrative analysis of genomic structural variants as cancer drivers
