Dr Vas Ponnambalam
- Position: Reader in Human Disease Biology
- Areas of expertise: Membrane receptors; soluble growth factors; lipid particles; signal transduction; membrane trafficking; endothelial cells; cardiovascular disease; cancer; diabetes
- Email: S.Ponnambalam@leeds.ac.uk
- Phone: +44(0)113 343 3007
- Location: 6.44c Garstang
- Website: | LinkedIn | Googlescholar | ORCID
BSc (1984), PhD (1988), University of Birminham. Seebe Fund postdoctoral research fellow at Stanford University, USA (1988-1991) and Cancer Research UK London research fellow (1991-1995). MRC Senior Research Fellow and Principal Investigator at the Wellcome Trust Biocentre & School of Life Sciences, University of Dundee (1995-2000). Lecturer in Molecular Cell Biology, University of Leeds (2000-2005), Senior Lecturer in Molecular Cell Biology (2005-2011), Reader in Human Disease Biology (2011-Present), Head of Endothelial Cell Biology Unit (2006-Present). Co-Director of the Leeds Bioimaging Facility.
PGR Admissions Tutor (International)
Member of Graduate School Committee
Faculty representative on Graduate Board Programmes of Study and Audit Group
The Astbury Centre for Structural Molecular Biology
My PhD training in bacterial genetics, enzymology and biochemistry (University of Birmingham, UK) was followed by postdoctoral training at Stanford University (USA) and Cancer Research UK (London, UK). During my postdoctoral training, I developed a long-term interest in membrane traffic and cell biology which continues to influence my current work in vascular biology. As an MRC Non-Clinical Senior Research Fellow and PI at the University of Dundee, I identified a key marker of the human Golgi apparatus (TGN46), and the reagents and antibodies to this protein has enabled this to become a standard biomarker for this compartment in different human cells and tissues.
As a faculty member at the University of Leeds, I have initiated a programme of work using the mammalian endothelium to better understand human health and disease by integrating techniques and systems in mathematical modelling, biophysics, biochemistry, cell biology, animal biology and clinical studies. My laboratory comprises both basic scientists and clinicans with a strong translational theme of a bench-to-bedside approach.
- Secretary of the British Society for Cell Biology
- Faculty International Postgraduate Tutor
- Biological Sciences Level 3 Year Tutor
Structure and Function of Receptor-Ligand Complexes which Regulate Angiogenesis and Vascular Physiology["Integrative Membrane Biology<\/a>","Cardiovascular, Sports and Exercise Sciences<\/a>","Cancer Research<\/a>"]
The mammalian vascular network is made of different cell types that cooperate to regulate blood vessel formation and vascular physiology. The endothelial cell monolayer that lines all blood vessels plays key roles in diverse phenomena including new blood vessel sprouting (angiogenesis), blood pressure, wound healing, atherosclerosis and cancer. My laboratory is investigating how growth factors and lipid particles which circulate in the blood regulate signal transduction and endothelial function in health and disease. Understanding how endothelial cells function in sensing such substances is needed for developing new therapeutics and diagnostics in heart disease, cancer, ocular diseases and pre-eclampsia. Areas from which our research benefits from collaborations within Leeds include the Endothelial Cell Biology Unit which comprises the groups of Ponnambalam, Homer-Vanniasinkam and Walker with an ethos of basic science translation into medicine. Cardiovascular research and translational research is further fostered by links to groups within the MultiDisciplinary Cardiovascular Research Centre (MCRC) and Biomedical Health Research Centre. We are carrying out structure-function studies through collaborations with the Astbury Centre for Structural Molecular Biology. We are collaborating with physical sciences experts to discover new therapeutics and ways of investigating biological function with the School of Chemistry and School of Mathematics.
The upper panel depicts a schematic of receptor-ligand activation, intracellular signalling, trafficking and proteolysis with changes in cellular outcomes such as cell proliferation, migration and apoptosis. The lower panels depict wide-field deconvolution microscopy images of primary human endothelial cells stained for key vascular marker proteins such as Von Willebrand Factor (VWF) and platelet-endothelial adhesion molecule 1 (PECAM-1). Each image comprises a projected stack of 15-20 optical sections, each of 0.4 microns thickness. Bar, 20 microns.
1) VEGFR-VEGF regulation of endothelial function. Vascular endothelial growth factors (VEGFs) comprise a multigene family encoding multiple isoforms and variants. VEGF-A can bind to VEGF receptor tyrosine kinases (VEGFR1, VEGFR2) on endothelial cells to activate signal transduction and multiple endothelial responses including cell migration, proliferation and angiogenesis i.e. the sprouting of new blood vessels from pre-existing ones. A major focus of the laboratory is the role of ubiquitination and de-ubiquitination in controlling VEGFR2 localisation, membrane trafficking and proteolysis and the implication for signal transduction and endothelial function.
2) Scavenger receptor regulation of vascular function & atherosclerosis. Scavenger receptors are membrane proteins that bind lipid particles, phospholipids and pathogens. The human lectin-like LOX-1 scavenger receptor binds oxidised low-density lipoprotein (OxLDL) and is implicated inc causing atherosclerosis leading to plaque formation and arterial blockage in different tissues. There is significant evidence linking LOX-1 to heart attacks, strokes and Type 2 diabetes. Understanding how LOX-1 regulates cell function and vascular physiology will enable us to target it for therapy and diagnosis of such disease states.
We have a long-term collaboration with Professor Ian Zachary (Centre for Cardiovascular Biology & Medicine, University College London, UK). Within Leeds, we collaborate with with Dr Darren Tomlinson, Dr Elton Zeqiraj (School of Molecular & Cellular Biology), Dr Michael Harrison, Dr Stephen Muench and Professor Paul Millner (School of Biomedical Sciences).We have ongoing projects with Professor Carmen Molina-Paris (School of Mathematics) and Professor Bruce Turnbull (School of Chemistry). Our clinical collaborators include cardiologists Dr Stephen Wheatcroft, Professor Mark Kearney, vascular surgeon Professor Shervanthi Homer-Vanniasinkam and clinical endocrinologist Dr Ramzi Ajjan (Leeds Institute for Cardiovascular & Metabolic Medicine).
Our current work is funded by the British Heart Foundation. Previous funding agencies for projects and equipment were from the Medical Research Council, The Wellcome Trust, BBSRC, The Circulation Foundation, European Union, Heart Research UK, The Leverhulme Trust, AstraZeneca, Yorkshire Cancer Research, Pfizer Global Inc., White Rose Network, Yorkshire Enterprise Fellowship scheme.
- Biochemistry BSc (Hons.), Birmingham
- Biochemistry PhD, Birmingham
- British Society for Cell Biology
- Biochemical Society
Teaching: I am Level 3 Tutor for Biological Sciences; Manager of Level 3 Skills Module for Biological Sciences; Level 3 specialist lectures on 'Signal Transduction & Heart Disease; Level 2 lectures in 'Vascular Diseases - Cancer & Atherosclerosis'; Level 2 lectures on 'Receptor tyroinse kinases, G-proteins &^ Lipid kinases'; Level 2 lectures on 'The Endothelium'.
Research projects for BSc, MBiol and MSc degree programmes: Vascular endothelial growth factor receptor (VEGFR) signal transduction and control of cell function, vascular physiology and human disease; Scavenger receptor regulation of vascular physiology, atherosclerosis and diabetes; Small molecules and synthetic proteins to target receptors and ligands in cell function and disease outcomes; Use of fluorescent reporters to monitor cell proliferation and function.
Undergraduate project topics:
- Receptor tyrosine kinase signal transduction and membrane trafficking
- Scavenger receptor signal transduction and membrane trafficking
- Synthetic protein-based targeting of membrane receptors and ligands
- Fluorescent reporters and imaging techniques in vascular biology
Postgraduate studentship areas:
- Vascular endothelial growth factor receptor (VEGFR) regulation of endothelial function, cardiovascular disease and cancer
- Scavenger receptor regulation of vascular phsiology, atherosclerosis and diabetes
- Ubiquitin-modifying enzyme function in vascular cells and tissues
- Faculty International Postgraduate Research (PGR) Admissions Tutor
- Member of Graduate School Committee
- Member and Faculty representative on Postgraduate Board Programmes of Study and Audit Group