Dave Bates
Research
I am also British Heart Foundation Senior Lecturer in Basic Biomedical Science and Scientific Director of the Microvascular Research Laboratories
Understanding how vascular growth factors (VEGFs) regulate microvascular function is a key hurdle in developing treatments for as varied disease types as cancer, diabetes, vascular disease, psoriasis, age-related macular degeneration, and arthritis. These seemingly diverse diseases are either characterised by excessive and uncontrolled microvascular growth and permeability, such as in cancer, psoriasis, arthritis and diabetic retinopathy, or by an insufficiency of vascular growth into damaged tissue, for instance in peripheral ischaemia, diabetic ulceration and coronary ischaemia. Moreover, VEGFs are critical in non-angiogenesis-dependent diseases such as ARDS and neurodegenerative pathologies, although the mechanism is still contentious.
A principal difficulty in understanding how VEGFs work is their pluripotent nature. VEGFs are potent vascular permeability agents, strong vasodilators, autocrine growth factors on many cell types, and stimulate lymphatic growth. We have investigated how these multiple pathways can be separated using multiple methods, including coincident measurement of vascular permeability and compliance (figure A1), developing models for measuring angiogenesis and lymphangiogenesis in physiological systems (see figure A2&3), and investigating autocrine signalling pathways in multiple cell types.
As a way of integrating these approaches, we have set up the University of Bristol Microvascular Research Laboratories, focussing on translating basic biological science to clinical relevance and therapeutic development. More details of the MVRL can be found on its website
The MVRL is an in-vivo applied laboratory of the University of Bristol Wellcome Trust 4 year PhD programme in Dynamic Cell Imaging , and also takes on students through BHF, cancer charity and eye charity funded programmes.
(Back to top)
Figure A1. Capillary in mesentery of frog perfused with rat red cells, and occluded to measure permeability in vivo Capillary diameter = 20µm.
Figure A2. Angiogenesis in the mesentery induced by Ad-VEGF165 infection of the surrounding fat pad (dark area). Blood vessels grow into the almost avascular connective tissue after 6 days. Scale bar = 100µm
Figure A3. Confocal image of sprouting blood vessel in a mesentery after injection with Adenovirus expressing VEGF165. In contrast to developing angiogenesis in the mouse, adult angiogenesis induced by potential therapeutic agents results in a single extension of the leading cell, which is likely to lead to less connections with other vessels. Scale bar = 8µm.
Links
Selected Publications
- Y. Qiu, H.S. Bevan, S. Weeraperuma, D. Wratting, D. Murphy, C.R. Neal, D.O. Bates, S J. Harper (2008)
Mammary alveolar development during lactation is inhibited by the endogenous anti-angiogenic growth factor isoform, VEGF165b.
Faseb Journal 2008 Apr;22(4):1104-12. - A.V. Benest, W.H. Millar, C. J. Glover, J B. Uney. A H. Baker, S J. Harper, D O. Bates. (2008)
Arteriolargenesis and angiogenesis induced by endothelial nitric oxide synthase overexpression results in a mature vasculature.
Arter Thromb Vasc Biol. 2008 (8):1462-8 - D.G. Nowak, J. Woolard, O. Konopatskaya, A.J. Churchill, S.J. Harper,M. Ladomery,and D.O. Bates. (2008)
Expression of pro- and anti-angiogenic isoforms of VEGF are differentially regulated by known splicing factors and environmental stimuli.
J Cell Sci 2008 121: 3487-3495 - V L. Bills, J Varet, A Millar, S J. Harper, P W Soothill D O. Bates (2008)
Low VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia.
Clinical Science - SJ Harper, DO Bates. (2008)
VEGF splicing ? the key to anti-angiogenic therapy?
Nature Cancer Reviews.In press.
.
A complete list of publications for 2008 can be found on the 'link' below
Publications link