Professor Cay Kielty holds a chair in Medical Biochemistry within the Wellcome Trust Centre for Cell-Matrix Research, and is Associate Dean for Research within the Faculty of Biology, Medicine and Health. She has a first class honours degree in Biochemistry from Kings College London and a PhD degree from University College London (1978). She joined the University of Manchester in 1981 as a post-doctoral research associate, and held consecutive MRC Senior Research Fellowships from 1993-2003. She led the Vascular and Tubular Structures programme within the UK Centre for Tissue Engineering (2001-2007) and the vascular programme of the UK Centre for Tissue Regeneration. Professor Kielty was elected as a Fellow of the Academy of Medical Sciences in 2001 and a member of Academia Europaea in 2009, and was awarded a Royal Society-Wolfson Research Merit award in 2004. She has served on many funding committees including the MRC Fellowships Panel, MRC Molecular and Cellular Medicine Board, and MRC Translational Stem Cell Research Committee. Professor Kielty is an expert in cell-matrix biology especially the assembly, structure and function of extracellular matrix, and in the biology and therapeutic applications of mesenchymal stem cells.

Professor Kielty's laboratory has two interconnected research themes: how the cell-matrix interface regulates extracellular matrix assembly and function, and how it regulates growth factor receptor signals in mesenchymal stem (progenitor) cells. The extracellular matrix is a complex multi-component structural microenvironment that is laid down by cells, and in turn supports cells and regulates their survival, migration, proliferation and behaviour. The matrix also stores growth factors which, upon release, activate cell receptors which signal intracellular to alter cell activity. We are studying vascular extracellular matrix (elastic fibres) and growth factor receptors. 

Assembly, Structure and Function of Fibrillin Microfibrils and Elastic Fibres

Extracellular matrix assembly studies focus on elastic fibres. The template for elastin deposition is fibrillin microfibrils, whose essential contribution to tissue integrity is highlighted by linkage of fibrillin mutations to Marfan syndrome which has severe cardiovascular, skeletal and ocular abnormalities. Microfibrils endow connective tissues with long-range elastic recoil, and microfibrillar structures include zonular fibres which hold the lens in dynamic suspension and oxytalan fibres which dispense elasticity to skin. Elastin is deposited on pre-formed microfibrils, in association with fibulins-4 and -5 and the crosslinking enzyme lysyl oxidase.

We are using recombinant elastic fibre molecules in combination with microscopy and in vitro binding studies to determine how elastic fibre molecules assemble, electron microscopy approaches to map tropoelastin binding sites on microfibrils, and biophysical approaches (analytical ultracentrifugation, laser light scattering) to study the process of multimerisation. We have developed a comprehensive mass spectrometry database of the molecular interactions of elastic fibres, including secondary associations mediated by heparan suphate. The roles of cell surface receptors in this process are being determined using knock-down and over-expression studies, in combination with biochemical approaches, confocal microscopy and real-time imaging. The effects of disease-causing mutations on elastic fibre assembly and function are also being addressed. 

Adult Mesenchymal Stem cells in Vascular tissue engineering

Our stem cell interests arose from adult mesenchymal stem cell (MSC) applications in vascular tissue engineering. We showed that vascular endothelial growth factor (VEGF) signals through platelet-derived growth factor PDGF) receptrs in MSCs, thereby regulating their migration, proliferation and tube-forming potential in culture (Ball et al., 2007, J Cell Biol. 177:489-500). We have shown that  PDGF receptors crosstalk with both integrins and neuropilin receptors expressed on MSCs, how this crosstalk regulates MSC phenotype, and the structural and signalling basis of growth factor ligand binding to PDGF receptors. This research has important implications for regulating neovascularisation. Using quantitative proteomic and glycomic approaches, we are defining the MSC cell-matrix interface and it regulates MSCs (collaborative studies with Profs Ann Canfield and Tony Whetton and Dr Cathy Merry).

We have two interconnected biomedical research themes. In the first theme, we are studying how cells make blood vessels. We are investigating how cells are able to lay down an intricate and stretchy structural framework that is made up of many different molecules, and how this elastic ‘matrix’ controls blood vessel function. This research focuses especially on a large structural molecule called "fibrillin" which, once outside cells, builds very long thin ‘microfibril’ structures. Bundles of these microfibrils then form the template for an important elastic protein called ‘elastin’. In the second theme, we are studying a type of adult stem cell called “mesenchymal stem cell” that occurs near blood vessels. These cells have great potential for tissue regeneration, both because they are able to become like cells from many tissues (including blood vessels, cartilage, bone and nerves), and because they produce ‘factors’ that limit inflammation after injury. We are finding out how their behaviour is controlled by interactions with their surrounding structural framework, and exploring how we may be able to use them to engineer new blood vessels to repair damaged tissues. Our research is funded by the Medical Research Council and the British Heart Foundation.