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Biography
I was the founding Director of the University of Nottingham Centre for Cancer Sciences from 2019-2024, and now a supportive member of the centre. My research focuses on teh mechanisms of alternative splicing in cancer, diabetes, and other diseases, as well as physiology. In particular I am interested in the microcirculation and growht and permeability of blood vessels.
I am also Chief Scientific Officer of IsomAb Ltd, a drug discovery company that is developing an isoform specific antibody to the VEGF-A165b isoform for cardiovascular disease.
I joined the University of Nottingham as Head of Division of Preclinical Oncology in 2013, and in the same year founded Exonate Ltd, a spin out company based on developing small molecules to regulate mRNA splicing with Prof Steve Harper at University of Bristol, Prof Lucy Donaldson at UoN and Prof Jonathan Morris from UNSW, based on our discovery of new potential drugs for eye disease, cancer and other conditions. Exonate now has successfully completed its phase Ib/IIa clinical trial as an eye drop for treatment of diabetic macular oedema. I am currently Chair of the SAB for Exonate Ltd.
In 2001 I was awarded a BHF Lectureship, and established the Microvascular Research Laboratories in Bristol. In that year I discovered a new class of VEGF molecules. I was appointed Professor of Microvascular Biology and Medicine in the Department of Physiology and Pharmacology in 2007, where I was responsible for a MSci in Physiology with a year in Industry and the second year BSc Physiology course for 120 undergraduate students per year. My laboratory has discovered how new VEGFs contribute to blindness, diabetes, cancer, lung and heart disease and other conditions, resulting in 10 patent applications and >150 peer reviewed papers in both scientific (Nature Medicine, Cancer Cell etc), and medical journals (Cancer Research, Clinical Cancer Research, Nature Reviews Cancer, etc).
I completed my PhD in 1992 at the University of London, on how and why patients treated for breast cancer develop swollen arms (lymphoedema). After a year learning molecular genetics of fruit flies at Glasgow University, I spent three years at the University of California at Davis, where I learned and extended a technique to measure how proteins and fluid move across the walls of individual capillaries, by putting tiny glass needles into the smallest blood vessels of the body. At this point I started investigating a new protein called VEGF - or vascular endothelial growth factor. I continued as a lecturer at the University of Leicester from 1996-1998, using novel chemicals, that were part of the process of developing new drugs now used as anti-cancer agents. I developed methods to investigate how VEGF works to cause blood vessels to grow, and moved to the University of Bristol as a British Heart Foundation (BHF) research fellow in the Department of Physiology in 1999.
Expertise Summary
My research focuses on how genes use alternative splicing to form proteins that can have opposite functions in cancer, heart disease, diabetes and other conditions as well as physiology. My interest in cancer research started by investigating how blood vessels control fluid exchange between blood and tissues - the permeability of the vessel wall, the interstital properties and the function of teh lymphatic system, particularly in breast cancer. I moved from tehre to investigate how blood vessels grow, and in particular how a protein called Vascular Endothelial Growth Factor (or VEGF) as well as other proteins made by the body can make new vessels form in health and disease.
This expanded to the role of blood vessel growth and permeability in cancers, heart and vascular disease (including atherosclerosis, coronary ischaemia, and peripheral vascular disease), diabetes, (including retinopathy, which causes blindness, nephropathy, which causes kidney failure, vasculopathy which can cause pain and peripheral ischemia, which can lead to ulcers and amputations). Other diseases that I work on include rheumatoid arthritis, renal disease, lymphatic diseases, and the basic causes of oedema (swelling).
I have always had a keen interest in working with low income countries to address pathologies that impact specifically, or more heavily on these populations. This has taken me to Thailand and PDR Lao to work on cholangiocarcinoma, a cancer of the bile duct, which is common in south east Asia, and to South Africa to work on colorectal cancer, prostate cancer and cervical cancer with African scientists and traditional healers.
These areas have led me into drug discovery research and collaborations worldwide, including with Prof Jonathan Morris in Australia working on compounds that inhibit splicing factor kinases, with Prof Zodwa Dlamini in South Africa on indigenous plant extracts, on antibodies to interstitial proteins with Prof Grith Sorensen in Denmark, and on repurposing anti-cancer agents and seaweed extracts with Profs Wongprasert and Tohtong in Thailand.
My work has been funded by major medical research charities such as the British Heart Foundation, The Wellcome Trust, Cancer Research UK and Diabetes UK, as well as by charities focussed on specific diseases such as teh AMMF (cholangiocarcinoma), Kidney Research UK, the Little Princess Trust (childhood cancers) and the Skin Cancer Research Fund (SCaRF). It has also received substantial support from the UK government through the UKRI route (MRC, BBSRC) as well as from Industry (Roche, Novo Nordisk), and from patent income.
Teaching Summary
Since moving to Nottingham I have led the development of a new undergraduate course in Cancer Sciences, the first of its kind in the UK, and potentially worldwide. The course now recruits up to 70… read more
Research Summary
I have programs focussing on controlling blood vessel growth in age related macular degeneration, diabetes, cancer of the bile duct, melanoma, basic mechanisms of blood vessel function (including… read more
Recent Publications
GRANT ZL, WHITEHEAD L, WONG VHY, HE Z, YAN RY, MILES AR, BENEST AV, BATES DO, PRAHST C, BENTLEY K, BUI BV, SYMONS RC and COULTAS L, 2020. Blocking endothelial apoptosis revascularises the retina in a model of ischemic retinopathy. The Journal of clinical investigation. (In Press.)
MAKHAFOLA, T. J., MBELE, M., YACQUB-USMAN, K., HENDREN, A., HAIGH, D. B., BLACKLEY, Z., MEYER, M., MONGAN, N. P., BATES, D. O. and DLAMINI, Z., 2020. Apoptosis in Cancer Cells Is Induced by Alternative Splicing of hnRNPA2/B1 Through Splicing of Bcl-x, a Mechanism that Can Be Stimulated by an Extract of the South African Medicinal Plant, Cotyledon orbiculata: Front Oncol Front Oncol. 10, 547392 BOONSRI, B., YACQUB-USMAN, K., THINTHARUA, P., MYINT, K. Z., SAE-LAO, T., COLLIER, P., SURIYONPLENGSAENG, C., LARBCHAROENSUB, N., BALASUBRAMANIAN, B., VENKATRAMAN, S., EGBUNIWE, I. U., GOMEZ, D., MUKHERJEE, A., KUMKATE, S., JANVILISRI, T., ZAITOUN, A. M., KUAKPAETOON, T., TOHTONG, R., GRABOWSKA, A. M., BATES, D. O. and WONGPRASERT, K., 2020. Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells: Cancer Res Treat Cancer Res Treat. HULL, R., MBELE, M., MAKHAFOLA, T., HICKS, C., WANG, S. M., REIS, R. M., MEHROTRA, R., MKHIZE-KWITSHANA, Z., HUSSAIN, S., KIBIKI, G., BATES, D. O. and DLAMINI, Z., 2020. A multinational review: Oesophageal cancer in low to middle-income countries: Oncol Lett Oncol Lett. 20(4), 42
Since moving to Nottingham I have led the development of a new undergraduate course in Cancer Sciences, the first of its kind in the UK, and potentially worldwide. The course now recruits up to 70 students a year. I led the course design, planning and resourcing, secured the pump priming from the University (£1.9M) to recruit 7 full time and 4 part time academic staff, leading a team of 5 academics to put this in place. I played a significant role in the curriculum development, and taught on all three years of the course. In 2023 I was awarded teh Lord Dearing Award for Teaching Excellence
Prior to this I had an extensive undergraduate teaching background, in Bristol, at the University of Leicester, UC Davis, and at St George's Hospital Medical School. I have redesigned modules (cardiovascular, molecular physiology and cell signalling), and implemented new modules (microcirculation), as well as taken responsibility for the running of the 2nd year course in Physiology in Bristol (120 students per year). The feedback I have had from the students that I have taught, have consistently described the lectures as entertaining, enthusiastic, and clear. I was particularly proud to note feedback on my second year teaching "Best lecturer of the year", particularly as I gave the last three lectures of the year immediately before the exams!