Decades of research have established how specific DNA sequences control genomic states associated with transcription, chromatin modifications and topological compartmentalization. However, besides helical, linear sequences, the DNA in the genome commonly adopts unusual, non-helical structural conformations. These alternative structural conformations, also referred to as secondary DNA structures, frequently form at guanine(G)-rich sequences and have been proposed to be functionally important in genome biology. One of our long-term goals is to understand the significance of non-B form DNA secondary structures in physiological states and pathological conditions. The roles of specific DNA sequences in genome biology are well-characterized, but how DNA structures influence functional genomic states is poorly understood.
We are currently focusing on understanding the roles of two major non-B DNA secondary structures in the genome, G-quadruplexes and the associated DNA:RNA hybrids (R-loops). G-quadruplexes and R-loops occupy evolutionarily conserved sites and, are implicated in modulation of gene expression, alterations in chromatin states and maintenance of genomic stability. They have been linked to pathological conditions, including neurodegenerative diseases and cancers. While our knowledge regarding the biology of G-quadruplexes and R-loops is still in its infancy, my current research strongly suggests their central role in regulation of transcription, chromatin accessibility, genomic compartmentalization and many other critical facets of genome biology. As first-steps towards understanding the functions of these structures, we aim study the abundance of G-quadruplexes and R-loops in normal and cancer genomes, epigenetic mechanisms regulating their localization and dynamics and, cellular pathways controlled by these structures.