Research

Epigenetics: DNA Modifications and Their Inheritance

Our lab investigates the dynamic landscape of DNA modifications, with a particular focus on their roles in epigenetic regulation and inheritance. Epigenetics refers to heritable changes in gene expression that occur without alterations to the underlying DNA sequence. Among the most studied epigenetic marks is DNA methylation, primarily the addition of a methyl group to the 5-position of cytosine (5mC), which plays a crucial role in gene silencing, genomic imprinting, and the maintenance of cellular identity.

A central question in our research is: How are DNA modifications faithfully inherited during DNA replication and cell division? While DNA methylation patterns are generally preserved through the action of maintenance DNA methyltransferases (e.g., DNMT1), the fidelity and regulation of this process remain incompletely understood, especially in the context of dynamic developmental and environmental cues.

We are particularly interested in the role of TET (Ten-Eleven Translocation) oxygenases, a family of enzymes that catalyse the stepwise oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). These oxidized derivatives are not only intermediates in active DNA demethylation pathways but may also serve as stable epigenetic marks with distinct regulatory functions.

Our research aims to dissect the molecular mechanisms underlying both passive and active DNA demethylation: Passive demethylation occurs when oxidized cytosine derivatives are not recognized by maintenance methyltransferases during DNA replication, leading to a dilution of the methylation mark over successive cell divisions.

Active demethylation involves enzymatic removal of modified cytosines, often through base excision repair pathways initiated by thymine DNA glycosylase (TDG) and other repair enzymes.

By combining biochemical, genomic, and computational approaches, we seek to understand how these processes are orchestrated in different cellular contexts as well as environmental and physiological cues and how they contribute to development, differentiation, and disease.

Epitranscriptomics: RNA Modifications in Gene Regulation and Physiology

Our lab investigates the fascinating world of RNA modifications - chemical marks on RNA molecules that add a new layer of gene regulation beyond the genetic code. This field, known as epitranscriptomics, is rapidly expanding our understanding of how cells control gene expression in space and time.

We study how RNA modifications influence key processes such as transcription, translation, RNA stability, and localization. These modifications are found across all major RNA types, including messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and long non-coding RNAs (lncRNAs). They play essential roles in cellular adaptation, development, and stress responses, and are increasingly recognized as critical regulators of genome stability and cellular physiology.

A particular focus of our research is the interplay between RNA modifications and the epigenome. We aim to understand how these two regulatory layers cooperate to fine-tune gene expression and maintain cellular identity across different physiological states.

By combining long-read sequencing technologies, molecular biology, and computational analysis, we seek to uncover the molecular mechanisms by which RNA modifications shape gene expression programs and respond to physiological signals. Our goal is to build a more integrated view of how the epitranscriptome and epigenome cooperate to maintain cellular function and adaptability.