Research groups

The research in the TVBL currently includes five groups focussing on vascular biology, cancer genetics, pain mechanisms, hypoxia/acidosis, and microvascular imaging.

Group leaders

 David Bates, Professor of Oncology

My research focusses on the biology of VEGF, regulation of angiogenesis, vascular permeability and control of splicing.

Kevin Gaston, Professor of Cancer Science

The focus of my research is on transcription factors and the roles that these proteins play in tumourigenesis.

Abdol Shams Nateri, Associate Professor

My research aims to obtain insights into the development and the pathological events that lead to the cancer of the gut and to understand the molecular mechanism of the links between signalling, transcription and diseases that control the nature of a "stem cell niche".

Alan McIntyre, Associate Professor

My research focuses on understanding the molecular and cell biology of the hypoxic microenvironment.

Andrew Benest, Assistant Professor

Endothelial quiescence & Transcriptomics - Understanding molecular mechanisms of blood vessel growth in health and disease

Kenton Arkill, Assistant Professor

My research focuses on developing 3D light and electron microscopy techniques in order to better describe the microcirculation.

The TVBL Resources.

Facilities

The TVBL is a shared 500m² laboratory that houses approximately 30 scientists  and PhD students focusing on areas of cancer cell biology and vascular biology. We have state of the art facilities in the lab for cell culture and cell phenotyping (including elecrical cell impedence and permeability measurement), epifluorescence and confocal microscopy, image analysis, mas spectroscopy, multiplate analysis, microdissection, protein, RNA and DNA analysis, molecular biology, digital droplet PCR, etc and access to the in vivo biology laboratories and cancer studies unit for physiological investigation of cancer and blood vessel function.

Vacancies

We have three postdoctoral positions positions available in the TVBL at the moment (August-Sept 2018).

Postdoctoral Positions

Postdoc in Vascular Biology

We are seeking a self-motivated, dynamic and dedicated postdoctoral research assistant to join the new Benest lab.  The project will aim to unravel transcriptional control of endothelial quiescence during development, and pathological conditions.  The project is funded by the British Heart foundation.  You will be  a member of a new and dynamic research group, working closely with a new PI within the TVBL.  Opportunity to co-supervise undergraduate and Masters students, and attend international conferences will be provided.

The ideal candidate will have, or be close to obtaining their PhD, preferably with a working knowledge of endothelial cells.  Full training in several animal models will be given, but an appreciation of how complex in vivo systems can be studied at a transcriptomic, and cellular level would be advantageous.

The is a fulltime 2 year post. To express an interest in this post email: Andrew.Benest@nottingham.ac.uk

Postdoc in Translational Cardiovascular Research

The Tumour and Vascular Biology Laboratories (www.tvbl-nottingham.org) in the School of Medicine seeks to appoint a postdoctoral research fellow to investigate the potential for a new treatment for peripheral ischemic disease.  This BHF funded position in Prof Bates' lab will focus on determining whether a new treatment for arterial disease can be generated using a monoclonal antibody to anti-angiogenic VEGF isoforms. You will be expected to have a PhD in Physiology, Cell Biology, Biochemistry or relevant subject and an emphasis on cardiovascular biology, preferably with experience of in vivo models of ischemia, immunoprecipitation, cell biology assays and biochemical assays. You will work within a large and exciting team focussing on diverse problems from trying to find treatments for cardiovascular disease, cancer and blindness to understanding basic mechanisms of cell biology.

The Project
The development of new vessels in health and disease is dominated by vascular endothelial growth factor-A (VEGF). One family of VEGF splice forms is pro-angiogenic, pro-permeability and vasodilatory (e.g. VEGF₁₆₅). We were the first to identify a sister family of isoforms that have opposing properties (e.g. VEGF₁₆₅b) and are expressed in normal human tissues, and upregulated in patients with arterial disease. In numerous in vivo angiogenesis models the angiogenic phenotype of VEGF has been shown to depend on the balance of its isoform families, such that control of VEGF₁₆₅b is now in clinical development as a therapeutic in human angiogenic eye disease.  To identify the angiogenic potential of regulating VEGF isoform availability in patients with arterial disease, we have developed antibodies with therapeutic potential. We are optimising these antibodies, and  will test whether they can stimulate re-growth of blood vessels in cellular and animal models of disease. This study could lay the basis for a new class of therapeutic strategies for vascular disease. 

To express an interest in this post email: David.Bates@nottingham.ac.uk

Postdoc in Neuroendocrinology and Angiogenesis

Project title: Angiogenic mechanisms underlying seasonal adaptation to a changing environment.
Duration: 36 months. Salary: Grade J, £36,613 / £41212 per year.
Funding body: BBSRC
We are seeking a flexible postdoc prepared to work based in Bristol, but also spending up to a year in the TVBL in Nottingham. This three way collaboration between the Universities of Bristol, Nottingham and Aberdeen will investigate the role of angiogenesis in neuroendocrine control of seasonal adaptation in horses, sheep and hamsters. Candidates must hold a PhD or equivalent in Neuroendocrinology, Chronobiology, Angiogenesis, or Physiology. The successful candidate must possess outstanding experimental and laboratory skills relevant to this role, as well as demonstrable success in in vivo work, tissue culture and data management. Practical experience in the use of research methodologies and techniques in molecular biology are essential for this post.

We have recently shown that a mechanism regulating angiogenesis within the pituitary gland participates in the seasonal adjustment of photoperiodic species to a changing environment by: a) controlling the remodelling of the pituitary microvasculature; and b) acting as messenger signals from the melatonin sensitive pars tuberalis (PT) to the endocrine cells of the pars distalis involved in the regulation of seasonal fertility. Here we will investigate whether this is a conserved system of adaptation, operating in species that reproduce at different times of the year, and examine the intra- and inter-cellular pathways underlying this process. It is well established that the pattern of melatonin secretion from the pineal gland decodes day length information through a direct action in the PT. The overall hypothesis of this project is that differential expression of VEGF-A isoforms within the pituitary participate in the melatonin signal readout to translate photoperiodic cues into an annual physiological response. We will investigate melatonin-induced VEGF-A alternative splicing and assess the implication of clock genes in the VEGF-A regulation of seasonal physiology using whole animal systems and in vitro strategies.

To express an interest in this post email: David.Bates@nottingham.ac.uk

Technician Positions

We are currently interviewing for a full time technician in the TVBL. Watch this space for more opportunities.

PhD Studentships

 Click here to see opportunities. We also have self funded studentships available listed by PI.

Upcoming and recent Events

We have a dynamic and active training and social programme. Friday afternoon Cancer Biology seminars (including regional food and drink) start again in September 2019

Seminar Series

Recent Publications (2018)

(Bold = current lab members, italics = Nottingham linked labs)

Tridgett M, Lozano L, Passaretti P, Desai NR, Proctor TJ, Little HA, Logan RT, Arkill KP, Oppenheimer PG, Dafforn TR.Dye Aggregate-Mediated Self-Assembly of Bacteriophage Bioconjugates.
Bioconjug Chem. 2018 Nov 21;29(11):3705-3714. doi: 10.1021/acs.bioconjchem.8b00617. Epub 2018 Oct 31.

Onions K, Gamez M, Buckner NR, Baker SL, Betteridge KB, Desideri S, Dallyn BP, Ramnath R, Neal CR, Farmer LK, Mathieson PW, Gnudi L, Alitalo K, Bates DO, Salmon AHJ, Welsh GI, Satchell SC, Foster RR.
VEGFC Reduces Glomerular Albumin Permeability and Protects Against Alterations in VEGF Receptor Expression in Diabetic Nephropathy. Diabetes. 2018 Nov 2. pii: db180045. doi: 10.2337/db18-0045. [Epub ahead of print]

Descamps B, Saif J, Benest AV, Biglino G, Bates DO, Chamorro-Jorganes A, Emanueli C. BDNF (Brain-Derived Neurotrophic Factor) Promotes Embryonic Stem Cells Differentiation to Endothelial Cells Via a Molecular Pathway, Including MicroRNA-214, EZH2 (Enhancer of Zeste Homolog 2), and eNOS (Endothelial Nitric Oxide Synthase). Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2117-2125. doi: 10.1161/ATVBAHA.118.311400.

Muhammad BA, Almozyan S, Babaei-Jadidi R, Onyido EK, Saadeddin A, Kashfi SH, Spencer-Dene B, Ilyas M, Lourdusamy A, Behrens A, Nateri AS. FLYWCH1, a Novel Suppressor of Nuclear β-catenin, Regulates Migration and Morphology in Colorectal Cancer. Mol Cancer Res. 2018 Aug 10. pii: molcanres.0262.2018. doi: 10.1158/1541-7786.MCR-18-0262. [Epub ahead of print]

Chung GHC, Domart MC, Peddie C, Mantell J, Mclaverty K, Arabiotorre A, Hodgson L, Byrne RD, Verkade P, Arkill K, Collinson LM, Larijani B.Acute depletion of diacylglycerol from the cis-Golgi affects localized nuclear envelope morphology during mitosis. J Lipid Res. 2018 Aug;59(8):1402-1413. doi: 10.1194/jlr.M083899. Epub 2018 Jun 12.

Bates DO, Beazley-Long N, Benest AV, Ye X, Ved N, Hulse RP, Barratt S, Machado MJ, Donaldson LF, Harper SJ, Peiris-Pages M, Tortonese DJ, Oltean S, Foster RR. Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators. Compr Physiol. 2018 Jun 18;8(3):955-979. doi: 10.1002/cphy.c170015.

Bestall SM, Hulse RP, Blackley Z, Swift M, Ved N, Paton K, Beazley-Long N, Bates DO, Donaldson LF.
Sensory neuronal sensitisation occurs through HMGB-1-RAGE and TRPV1 in high-glucose conditions. J Cell Sci. 2018 Jul 26;131(14). pii: jcs215939. doi: 10.1242/jcs.215939.

El Ansari R, McIntyre A, Craze ML, Ellis IO, Rakha EA, Green AR. Altered glutamine metabolism in breast cancer; subtype dependencies and alternative adaptations. Histopathology. 2018 Jan;72(2):183-190. doi: 10.1111/his.13334. Epub 2017 Oct 17. Review.

Neal CR, Arkill KP, Bell JS, Betteridge KB, Bates DO, Winlove CP, Salmon AH, Harper SJ. Novel Haemodynamic Structures in the Human Kidney Am J Physiol Renal Physiol. 2018 Jun 20. doi: 10.1152/ajprenal.00566.2017. [Epub ahead of print]

Ved N, Da Vitoria Lobo ME, Bestall SM, L Vidueira C, Beazley-Long N, Ballmer-Hofer K, Hirashima M, Bates DO, Donaldson LF, Hulse RP. Diabetes-induced microvascular complications at the level of the spinal cord: a contributing factor in diabetic neuropathic pain. J Physiol. 2018 Aug;596(16):3675-3693. doi: 10.1113/JP275067. Epub 2018 Jul 11.

N Beazley-Long, F Almahasneh, W Ashby, SM Bestall, MN Swift, A Durrant, CE Moss, AV Benest, RP Hulse, DO Bates, LF Donaldson. VEGFR2 promotes central endothelial activation and the spread of pain in inflammatory arthritis Brain Behaviour and Immunity. 2018 Mar 14. pii: S0889-1591(18)30060-6

SL Barratt, T Blythe, K Ourradi, C Jarrett, GI Welsh, DO Bates, AB Millar  Effects of hypoxia and hyperoxia on the differential expression of VEGF-A isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF). Respir Res. 2018 Jan 15;19(1):9

M Stevens, CR Neal, AHJ Salmon, DO Bates, SJ Harper, S Oltean. VEGF-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury. Nephron In Press

Posters

Exonate Ltd is a spin out company of the TVBL, focussed on developing treatments for diseases involving altered splicing, particularly of VEGF.

Funding

Our funding comes from multiple sources. We gratefully acknowledge funding from the following bodies