Ewch i’r prif gynnwys
Dr Youcef Mehellou

Dr Youcef Mehellou

Lecturer

Ysgol Fferylliaeth a Gwyddorau Fferyllol

Ar gael fel goruchwyliwr ôl-raddedig

I joined School of Pharmacy and Pharmaceutical Sciences at Cardiff University as a Lecturer in Medicinal Chemistry in January 2017. Prior to this, I held a lectureship position at the University of Birmingham.

After receiving my MPharm degree from King’s College London in 2005, I joined the lab of Prof. Chris McGuigan at Cardiff University for a PhD in Medicinal Chemistry. In early 2009, I moved to Arizona State University (USA) to work as a postdoctoral scientist with Prof. Sidney M. Hecht on the synthesis of unnatural amino acids. In mid-2010, I was awarded an MRC Career Development Fellowship that was held in the lab of Prof. Dario R. Alessi, University of Dundee, until March 2013 when I joined the University of Birmingham.

I have a major interest in the discovery of chemical strategies that manipulate signal transduction. My current projects fall under two major themes:

  • Development of new therapeutic phosphate prodrugs
  • Discovery of therapeutic protein-protein interaction inhibitors

Lab Webpage: www.mehelloulab.com

Qualifications

  • MPharm (Pharmacy), King’s College London, 2005.
  • PhD in Medicinal Chemistry. Cardiff University, 2009.

I obtained my Ph.D. from the Welsh School of Pharmacy, Cardiff University. My postgraduate research was carried out in the laboratory of Prof. Christopher McGuigan. The project was on the design, synthesis and development of nucleoside analogues and their phosphate prodrugs (Phosphoramidates) as potential antiviral and anticancer therapies. During this work, I synthesised a large number of nucleoside analogues and their phosphoramidate derivatives and explored their potential as antiviral and anticancer compounds in collaboration with Prof. Jan Balzarini. I used molecular modelling as well as NMR studies to investigate the differences in biological activities seen with some of the nucleoside analogues phosphoramidates.

This was followed by a Postdoc with Prof. Sidney M. Hecht at the Biodesign Institute, Arizona State University, USA. My work then was on the development of chemical strategies that allow the incorporation of unnatural amino acids into proteins. This involved the synthesis of unnatural amino acids and ligating them to synthetic dinucleotides.

In late 2010, I took a position as an MRC Career Development Fellow with Prof. Dario R. Alessi (FRS) at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU), University of Dundee. While in this position, Youcef’s work was concerned with the regulation of the catalytic activity of kinases, particularly SPAK, OSR1 and MSTs, by the scaffolding protein MO25. Youcef solved the crystal structure of the kinase MST3 in complex with MO25, which shed some light on the activation of kinases by MO25. Youcef also worked on developing high throughput screening assays for identifying small molecules that inhibit various components of the WNK signalling pathway of which SPAK and OSR1 kinases are part of.

Anrhydeddau a Dyfarniadau

  • MRC Career Development Fellowship (2010-2013).

Aelodaethau proffesiynol

  • Member of the Biochemical Society.
  • Member of the Royal Society of Chemistry.
  • Member of the Biochemical Society Signalling theme Panel.

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2007

My research is highly interdisciplinary and involves techniques and skills that span Synthetic and Medicinal Chemistry, Biochemistry and Crystallography. Current active projects:

Design, synthesis and biological evaluation of phosphate prodrugs

Developing platform technologies that allow the delivery of phosphorylated molecules into cells is of great interest to us. We have great expertise in the synthesis and application of the phosphoramidate technology ('ProTide') [see Mehellou et. al. 2009, ChemMedChem, 4, 1779-91], which has been shown to be an effective technology in delivering nucleoside analogues monophosphates into cells. The application of this technology can turn inactive nucleoside analogues into active ones. Largely, this technology is known to significantly improve the pharmacological activity of nucleoside analogues.

Our current efforts are focused on introducing new chemical modifications to the 'ProTide' technology to achieve tissue-specific delivery. Additionally, we are applying the 'ProTide' technology to discover nucleotide therapeutics that can treat diseases with unmet medical needs.

Discovery of therapeutic protein-protein interaction inhibitors

We employ chemical approaches to decode cellular signal transduction networks. Currently, we are in the process of translating our current understanding of the regulation of SPAK and OSR1 kinases into small molecules that manipulate their function. Current efforts include designing and synthesising a series of small molecules that have the potential to manipulate SPAK/OSR1 signalling. To achieve this, we are using crystallography, virtual screening, chemical synthesis and biological testing of the synthesised compounds.

Further details can be found @ http://mehelloulab.wixsite.com/lab1