My research focus is the structure/function relationships of glycosaminoglycans (GAGs) and the role of the microenvironment in directing cell behaviour. Since 2006 I have developed a biomaterials expertise, primarily as a way of displaying GAGs to cells and to generate artificial microenvironments - a key priority for regenerative medicine.
I began my research career working with Prof. John Gallagher in Manchester where I developed the first method for sequencing the complex carbohydrate, heparan sulphate. A growing interest in the biological role of proteoglycans encouraged me to seek out new research areas, including an investigation of the molecular phenotype of a mouse mutant for a component of the HS biosynthetic pathway and subsequently, a mouse lacking a critical HS modification enzyme.
Having established GAG analytical and stem cell differentiation tools during my PhD and post-doctoral studies, I was keen to develop my experience and establish my own group. I aimed to consolidate and exploit the unique position I had established within the field and to address what I perceived to be an important and currently under-exploited niche within the stem cell community, that of the use of GAGs to direct cell behaviour for tissue engineering and regenerative medicine applications. I therefore left the Paterson Institute/Christie Hospital to take up a lectureship in the School of Materials in the University of Manchester. We published the first characterisation of mouse ES cell heparan sulphate in 2007 and demonstrated how the sulphation patterns altered during neural differentiation. In 2008, we were able to show how antibodies specific for HS patterns could be used to fractionate cell populations during ES cell differentiation, separating cells with distinct fates.
In 2011 my group was the first to describe how GAGs drive lineage-specific ES cell differentiation; a key goal for cell/tissue engineering, with publications in Stem Cells and J. Biol. Chem. and invited presentations at international stem cell/matrix biology meetings. In late 2012 our demonstration of how GAGs displayed on fibrous scaffolds influence stem cell differentiation was published in J. Biol. Chem. and a paper describing GAG display on hydrogels is in preparation following patent protection of the hydrogel technology. The role of GAGs is also critical for stem cell/niche interactions and this has led to many exciting collaborations, where my unique contribution to GAG analysis and the use of biomaterials to mimic niche has a major role.
My collaborative projects, in particular my long-term collaborations with Prof. Lena Kellen (Uppsala University), Prof Toin van Kuppevelt (University of Nijmegen, The Netherlands), Prof. John Whitelock (UNSW, Australia) and Professors Tony Day and Doug Dyer (Wellcome Trust Centre for Stem Cell Research, University of Manchester) have also been highly productive, with publications, significant grant funding and joint PhD studentship awards.
Since moving to The University of Nottingham in September 2015 I work closely with Prof. Chris Denning (Wolfson Centre for Stem Cells, Tissue Engineering and Modelling), Dr Beth Coyle (CBTRC), Dr Anna Grabowska (Medicine), Dr Alexander Thompson (Stem Cells), Dr Amanda Wright (Optics and Photonics) as well as Dr Kenton Arkill (http://www.tvbl-nottingham.org/Evil/index.html) and Prof. Morgan Alexander (Next Generation Biomaterials Discovery) building a research base in modelling diseases of the extracellular matrix and improving our understanding of how glycosylation of stem cells influences their function. My group is housed in world-class facilities including dedicated cell culture suites and extensive biochemical and molecular biology labs
PIJUAN-GALITÓ S, TAMM C, SCHUSTER J, SOBOL M, FORSBERG L, MERRY CL and ANNERÉN C, 2016. Human serum-derived protein removes the need for coating in defined human pluripotent stem cell culture. Nature communications. 7, 12170 HOLLEY RJ, TAI G, WILLIAMSON AJ, TAYLOR S, CAIN SA, RICHARDSON SM, MERRY CL, WHETTON AD, KIELTY CM and CANFIELD AE, 2015. Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells. Stem cell reports. 4(3), 473-88
WATSON HA, HOLLEY RJ, LANGFORD-SMITH KJ, WILKINSON FL, VAN KUPPEVELT TH, WYNN RF, WRAITH JE, MERRY CL and BIGGER BW, 2014. Heparan sulfate inhibits hematopoietic stem and progenitor cell migration and engraftment in mucopolysaccharidosis I. The Journal of biological chemistry. 289(52), 36194-203