Our research is focussed on two main problems:
- Molecular mechanisms of generating tissue asymmetry
All tissue development and replenishment relies upon the breaking of symmetries i.e. the morphological and operational differentiation of progenitor cells into more specialized cells. One of the main engines driving this process is Notch signalling. We have used sprouting angiogenesis (blood vessel formation) as a model system to gain new insights into tissue patterning at the Notch ligand/receptor and the downstream transcription level.
- Identification and Characterization of Novel Small Molecule Inhibitors of ETS transcription factors
ETS transcription factors sit downstream of major signaling pathways and are essential for normal cell proliferation, growth and differentiation. In light of their established role in angiogenesis and in tumourigenesis, we collaborated with the Leiden Institute of Chemistry/ZoBio (NMR-based fragment screen) and also the European Lead Factory (ultra-high throughput small molecule screens) to identify novel small molecule inhibitors of the ETS transcription factors, the rationale being a simple two-birds-with-one-stone strategy to inhibit tumours by targeting both the tumour vasculature and the also the tumour cells. We are currently characterizing the resulting ‘hits’.
I did my PhD at the Royal Postgraduate Medical School (now Imperial College, London) studying receptor tyrosine kinase (RTK) signalling in leukaemia. Post-doctoral work was conducted at the Cancer Research UK London Research Institute (now part of The Crick Institute) and Imperial College London focussed on the molecular mechanisms of Notch signalling. I joined the Dept. Molecular Cell Biology (LUMC) as a group leader where we have continued to study the molecular mechanisms underlying tissue growth and differentiation.
Control of Endothelial Sprouting by a Tel:CtBP Complex.
Roukens MG, Alloul-Ramdhani M, Baan B, kobayashi K, Peterson-Maduro J, van Dam H, Sculte-Merker S, Baker DA.
Nature Cell Biology 12(10):933-942 (2010).
Functional analyses of a human vascular tumor FOS variant identify a novel degradation mechanism and a link to tumorigenesis.
van IJzendoorn DGP, Forghany Z, Liebelt F, Vertegaal AC, Jochemsen AG, Bovée JVMG, Szuhai K, Baker DA.
J Biol Chem. 2017 Dec 29;292(52):21282-21290
Control of endothelial cell tube formation by Notch ligand intracellular domain interactions with activator protein 1 (AP-1).
Forghany Z, Robertson F, Lundby A, Olsen JV, Baker DA.
J Biol Chem. 2018 Jan 26;293(4):1229-1242.
Groups: Transcriptional Regulation