The acquisition and maintenance of cell fate identities is essential for normal development and adult tissue physiology. However, the molecular mechanisms safeguarding cell fate identity remain largely unclear. Our interest is to determine the epigenetic and transcriptional programs underlying cell fate changes occurring during embryonic development, malignant transformations and aging restoration. Our main projects involve:
1) DNA oxidations:
TET enzymes are DNA dioxygenases that can sequentially convert methylated DNA (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These DNA oxidations are intermediates during DNA demethylation and can also serve as epigenetic elements regulating gene expression. We are investigating how TET-mediated DNA oxidations functioning as epigenetic elements regulate cancer dormancy and the restoration of aging.
2) Transcriptional pausing/elongation:
RNA Polymerase II (Pol II) promoter-proximal pausing is a regulatory step during transcription elongation. We are studying the interplay between epigenetic and transcriptional pausing in the context of aging restoration, early embryonic development and cancer dormancy.
3) Circadian rhythms:
Circadian rhythms are required for cellular and tissue homeostasis. Deficient circadian rhythms are implicated in various diseases. We are investigating how the epigenome modulates circadian rhythms and its impact in cell fate changes.