Dr Vas Ponnambalam
- Position: Reader in Human Disease Biology
- Areas of expertise: Membrane receptor structure-function; soluble growth factors and cytokines; 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: 6.04a Miall
- Website: | Twitter | LinkedIn | Googlescholar | ORCID
Profile
1981-1984 Biochemistry BSc, Dept. of Biochemistry, University of Birmingham, UK.
1988-1991 Biochemistry PhD, Dept. of Biochemistry, University of Birmingham, UK.
1988-1991 Seebe Fund postdoctoral research fellow at Stanford University, USA.
1991-1995 Cancer Research UK Research Fellow, London, UK.
1995-2000 MRC Senior Research Fellow, Principal Investigator, Wellcome Trust Biocentre & School of Life Sciences, University of Dundee, UK.
2000-2005 Lecturer in Molecular Cell Biology, University of Leeds, UK.
2005-2011 Senior Lecturer in Molecular Cell Biology, University of Leeds, UK.
2011-Present Reader in Human Disease Biology University of Leeds, UK.
2006-Present Head of Endothelial Cell Biology Unit, Faculty of Biological Sciences, University of Leeds, UK.
Following my BSc in Biochemistry, I undertook a PhD training in bacterial genetics, enzymology and biochemistry (University of Birmingham, UK)/ This 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, physiology and human disease. 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 reagents and antibodies to TGN46 has established this as a standard cellular marker in different human cells and tissues.
As a faculty member at the University of Leeds, working with basic science researchers and clinicians, I have developed a research programme aimed at better understanding human vascular health and disease ststes. We employ a multidisciplinary approach using 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.
Research interests
Receptor-Ligand Regulation of Cell and Animal Function in Health and Disease
The mammalian vascular network comprises 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, chemokines 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 is based on collaborations with basic science and clinical researchers including the groups of Ponnambalam, Harrison and Divan in the Faculty of Biological Sciences; Homer-Vanniasinkam and Wheatcroft in Faculty of Medicine & Health, with an aim of basic science translation into medicine. Cardiovascular research and translational research is further fostered by the MultiDisciplinary Cardiovascular Research Centre at the University of Leeds. Our work is underpinned by access to a access to a wide array of molecular, cellular, ex vivo and in vivo assays and facilities to support a variety of research projects.
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 binds to 2 different 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.
3) VEGF and chemokine regulation of vascular and immune function. VEGFs and chemokines have differing effects on vascular and immune function in normal physiology, development and disease states. We are exploring how VEGFs cooperate with chemokines to promote endothelial function and interaction with immune cells such as leukocytes during angiogenesis, inflammation and heart disease.
We have long-term collaborations with Professor Ian Zachary (Centre for Cardiovascular Biology & Medicine, University College London, UK) and Dr Caroline Pellet-Many (Royal Vet College, University of London). Within Leeds, we collaborate with with Professor Darren Tomlinson, Professor Elton Zeqiraj (School of Molecular & Cellular Biology), Dr Michael Harrison, Professor Stephen Muench (School of Biomedical Sciences) and Professor Steve Wheatcroft, Dr Nadira Yuldasheva, Professor Ramzi Ajjan (LICAMM, Faculty of Medicine & Health), and Professor Bruce Turnbull (School of Chemistry).
Our current work is funded by the British Heart Foundation. Previous funding agencies include 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.
Qualifications
- Biochemistry BSc (Hons.), Birmingham
- Biochemistry PhD, Birmingham
Professional memberships
- British Society for Cell Biology
- Biochemical Society
Student education
UG Teaching:Level 1, Level 2 and Level 3 teaching in Biochemistry, Biological Sciences, Biotechnology with Enterprise, Microbiology and Natural Sciences BSc and MBiol/MRes degree programmes
PGT Teaching: MSc teaching on Bioscience and HUman Health, Infection & Immunity MSc degree programmes
Laboratory and literature research projects for BSc, MBiol and MSc degree programmes. Topics include VEGFR signal transduction and cell function in health and disease; Scavenger receptor regulation of vascular physiology, atherosclerosis and diabetes; Small molecules and synthetic proteins that target receptor-ligand function and disease outcomes; Developing fluorescent reporters to monitor cell proliferation and cell 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
See also:
Committees
- Member of Athena Swan Committee
Research groups and institutes
- Cancer
Projects
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<li><a href="//phd.leeds.ac.uk/project/1903-new-molecules-and-mechanisms-in-angiogenesis">New molecules and mechanisms in angiogenesis</a></li>