Research Focus
Cells are constantly exposed to both environmental and endogenous genotoxic agents that threaten the integrity of their DNA. In response, they activate highly specialized DNA damage response (DDR) pathways that coordinate DNA repair with cell cycle checkpoint activation, chromatin remodeling, changes in gene expression, and metabolic adaptation. These pathways are essential for preserving genome stability and overall cellular function.
Defects in DDR pathways can have far-reaching consequences, contributing to a wide range of diseases and playing a central role in the ageing process. Genomic instability is a defining hallmark of nearly all cancers, and mutations in DDR genes drive both tumor initiation and progression. Similarly, the accumulation of DNA damage and the decline of repair efficiency are key contributors to ageing and age-related diseases such as neurodegeneration—underscoring the critical importance of DDR mechanisms in maintaining health throughout life.
DDR pathways are deeply interconnected with many aspects of cell biology. A striking example is the maintenance of telomeres, the specialized structures that protect chromosome ends. Telomeres are inherently fragile and rely on tightly regulated DDR activities to ensure their stability. Although telomere biology has been studied intensively, many key aspects of how DDR pathways interact with and regulate telomere maintenance remain unclear.
Another emerging and exciting area of research is the crosstalk between DNA repair and RNA metabolism. Recent discoveries have shown that the repair of certain types of DNA lesions depends on RNA processing events that occur directly at sites of DNA damage. This intersection between RNA biology and DDR is not yet fully understood, but it holds significant promise for both fundamental insights and therapeutic innovation.
OurResearch Questions
The overarching goal of our research program is to understand how DDR pathways interact with other cellular processes to preserve genome and cellular integrity. We are particularly focused on the following questions:
- How do DDR pathways crosstalk with telomere maintenance mechanisms?
We investigate how telomeres engage with DDR pathways to ensure telomere stability.
- How do RNA-binding proteins organize chromatin-based responses to DNA damage?
We study how RNA-binding proteins regulate the recognition, signaling, and repair of different types of DNA damage, particularly through their roles at damaged chromatin.
- How can insights into DDR mechanisms inform our understanding of disease and guide new therapeutic strategies?
By elucidating the molecular underpinnings of DDR pathways, we aim to uncover new opportunities for targeting genome instability in cancer and other diseases.
