Professor Natasha Harvey

Excludes commercial-in-confidence projects.

Research outputs for the last seven years are shown below. To see earlier years visit ORCID or Scopus

Open access indicates that an output is open access.

Chapters

Journal Articles

GATA2 is important for the development and maintenance of lymphatic vessel valves.

In collaboration with Professor Hamish Scott’s team at the Centre for Cancer Biology, we recently discovered that heritable mutations in the transcription factor GATA2 predispose carriers to lymphoedema and myelodysplasia syndrome (MDS)-acute myeloid leukaemia (AML) (Kazenwadel et al., Blood, 2012). This discovery revealed a key role for GATA2 in lymphatic vessels. We subsequently demonstrated that GATA2 is present at high levels in lymphatic vessel valves and that GATA2 regulates the expression of genes required for valve development. Our most recent work has established that GATA2 is required both to initiate the process of lymphatic vessel valve development and maintain the architecture of lymphatic vessel valves once they have formed (Kazenwadel et al., J Clin Invest, 2015). Our current work aims to define precisely how GATA2 regulates gene expression in the lymphatic vasculature to control valve development. Ultimately, our goals are: 1) To identify new therapeutic targets to which effective therapeutics for the treatment of lymphoedema could be designed. 2) To understand how valve endothelial cell identity is transcriptionally programmed and how this process could be manipulated to generate valves for therapeutic applications.

Regulation of vascular development by the ubiquitin ligase Nedd4.

Ubiquitination is a highly conserved process of protein modification that leads to the tagging of target proteins by one or more ubiquitin molecules. Ubiquitination can “flag” proteins for degradation, dictate their subcellular localisation and/or regulate protein trafficking through cellular compartments. As such, ubiquitination has crucial roles in regulating many signalling pathways and mis-regulation of this process is associated with numerous human pathologies. We have found that the ubiquitin ligase Nedd4 plays key roles in the growth and development of both blood vessels and lymphatic vessels. Our current work aims to dissect the endothelial cell autonomous versus non-autonomous roles of Nedd4 during vascular development and to define the signalling pathways regulated by Nedd4 that are important for vessel growth and remodelling.