Research

Vision

We are fascinated by the epigenetic mechanisms underlying the specialization of pluripotent stem cells into distinct cell lineages. How do epigenetic mechanisms contribute to establishment and maintenance of cell-type specific gene expression programs? How are epigenetic modification of chromatin dynamically regulated? How do they go awry in disease? Can they be targeted for therapeutic intervention?
Nucleosomes

Mission

We want to illuminate the epigenetic mechanisms that establish and maintain stable gene expression states. Ultimately, we aim to unravel the crosstalk between epigenetic regulation and cell plasticity.
Nucleosomes

Approach

In addition to genetic and biochemical analyses of chromatin regulatory activities, we apply innovative biosynthetic technologies which enable reversible targeting to directly interrogate the function in transcriptional gene regulation in vertebrate cells. By integrating small molecule-dependent control with precise biochemical analyses of chromatin changes, we systematically resolve the contributions of different modifying-activities to form repressive chromatin structure, as well as to initiate and propagate gene silencing. This reductionist approach to recapitulate complex chromatin landscapes offers a unique entry point to use genetic and pharmacological tools to dissect the mechanism of epigenetic regulation. In addition, kinetic measurements at high temporal resolution enable mathematical modelling of complex histone modification dynamics and patterns.
Nucleosomes

Impact

We aim to identify and understand the regulatory feedback mechanisms that facilitate robust maintenance of gene expression states through the massive chromatin reorganisation entailed by genome replication. As key regulators of this process have been implicated in tumorigenesis, elucidating the molecular underpinnings of normal and aberrant chromatin regulation is critical on the path to developing effective clinical therapies.