Department of Pharmacy and Pharmacology
melanie_welham

Visiting Professor

Email: M.J.Welham@bath.ac.uk

Prof Melanie Welham 

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Molecular Signalling and Regulation of Embryonic Stem Cell Fate

The Welham laboratory has focussed on understanding how molecular signals are coupled to the functional responses of target cells for many years. The primary interests of the group now focus on how signalling processes regulate the behaviour of embryonic stem cells (ESCs).

ESCs have two key properties: (i) Self-renewal – meaning they are able proliferate almost indefinitely while retaining an undifferentiated phenotype and (ii) Pluripotency – the ability to differentiate into all cells of an adult organism. We are addressing questions that are fundamental to our understanding of ESC behaviour, and key to their eventual exploitation, by investigating the molecular signals regulating ESC pluripotency and self-renewal as well as those controlling endoderm and mesoderm differentiation.

Regulation of ES cell self-renewal

We demonstrated that signalling via the phosphoinositide 3-kinase (PI3K) pathway plays an important role in maintenance of mouse ESC self-renewal (Paling et al., 2004), controlled at least in part by the ability of PI3K signalling to regulate expression of the transcription factor Nanog (Storm et al., 2007; 2009; Welham et al., 2011). Using transcriptional profiling, we defined the PI3K-dependent transcriptome and are currently focusing on the role of the Zscan4 family in ESC fate regulation (Storm et al., 2009). We have also demonstrated a key role for Glycogen synthase kinase-3 (Gsk-3) in promoting pluripotency of mouse ESCs (Bone et al., 2009; Welham et al., 2011) and are continuing to investigate its mode of action.

Regulation of ES cell Differentiation

We have previously used mouse ESCs as an in vitro model for developmental haemopoiesis (Paling et al., 2005; Bone and Welham, 2007). More recently, in collaboration with Prof David Tosh, we have focussed on exploiting small molecule-based approaches to chemically direct differentiation of human ESCs (Bone et al., 2011), with a view to generating functional hepatocyte-like cells for use by the pharmaceutical industry in toxicity screening.

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