For over a decade William has worked on how stem cells integrate extrinsic and intrinsic signals to manifest phenotype in the hope of better controlling their therapeutic potential. During William’s PhD studies William challenged existing dogma about the role of mitogenic signalling in regulating stem cell behaviour and showed that ERK signalling regulated lineage specific differentiation, rather than a general differentiation cue as previously thought.

William expanded along this line for my postdoctoral research, taking this project with him on the move to Copenhagen, and published a series of articles, precisely delineating the molecular mechanisms underpinning ERK-dependent lineage specifications, culminating in the publication in Nature of the largest, systemwide analysis of the response to ERK activation to date. In doing this we made available over 300 genome-, transcriptome- and proteome-wide datasets to the scientific community. Moreover, this work uncovered a novel transcriptional mechanism that explains the phenomenon of lineage priming: the ability of cells to partly progress down one lineage trajectory whilst maintaining the capacity to reengage with an early stem cell state. This knowledge has led to the development of methods which enhance in vitro stem cell differentiation, specifically with respect to early endodermal lineages.