Most animal life begins with the union of a sperm and an egg. The newly formed zygote develops under precise regulation, undergoing in vivo reprogramming to gain the potential to become any cell type and eventually a whole organism. While we have gained some understanding of this process, many of the underlying mechanisms remain unknown. For example, what are the factors and regulatory networks that orchestrate reprogramming and differentiation? And what happens when these regulators malfunction?

Answering these questions not only helps us decode how life begins but also provides critical insights into disease, including cancer. To address them, our lab uses zebrafish as a model organism and integrates advanced genetics, genomics, and imaging approaches. We focus on two main areas:

• Development: DNA is normally wrapped around histones, forming a “closed” chromatin structure that restricts access to genes. Certain transcription factors, known as pioneer factors, can open this closed chromatin and allow genes to be activated. Because chromatin opening is thought to be the first step in gene regulation, pioneer factors are likely to play key roles in development. However, only a few pioneer factors are known. We aim to uncover the pioneering networks that drive in vivo reprogramming and differentiation. How do pioneer factors regulate chromatin, from DNA to 3D genome architecture, to orchestrate the developmental rhythm? And how does chromatin itself influence pioneer factor activity and specificity?
• Disease: What happens when pioneer factors malfunction? Many pioneer factors are implicated in cancer. We study how oncogenic pioneer factors, or pioneer factors with oncogenic mutations, drive tumor formation. By understanding their mechanisms, we aim to explore whether disrupting their activity could help prevent or treat cancer.