Understanding and controlling cell state transitions

The lab’s research is centred around the in-depth profiling of transcriptional and epigenetic changes that occur during cellular transitions, to understand their molecular basis and importantly, to control them. In this context, we study cell fate conversions that occur rapidly as a consequence of forced cellular reprogramming, as well as the subtler and slower, albeit functionally meaningful, changes that occurring as part of developmental maturation and during ageing.

Research overview

Transdifferentiation and induced pluripotent stem cell (iPSC) technologies are forms of transcription factor (TF)-mediated cell reprogramming. This is achieved by the overexpression of a set of key TFs in a given cell type to induce reprogramming into another cell type.

Age is one of the greatest risk factors for most degenerative diseases of mid- and late life and meaningful therapeutic control over the ageing process would be revolutionary. On a cellular level, ageing appears to be a largely epigenetic phenomenon that can be manipulated by pluripotency induction or transient expression of iPSC reprogramming factors.

As such, functionally compromised aged blood stem cells can be reprogrammed into iPSCs and used to generate young healthy animals with a normal hematopoietic system and (PMIDs: 28224997, 23476050). Accordingly, if we understand the cellular age-state with its associated epigenetic signature well enough, direct strategies might be implemented to edit cellular age without a need for pluripotency induction.

Among other things, the Nefzger lab investigates why youthful cell identity deteriorates over time and explores the use of transcription factors and epigenetic modifiers to directly covert aged cells towards a more functional state without affecting cell type identity.