Professor Roy Bicknell MA, D.Phil, FSB

Professor Roy Bicknell

Institute of Cardiovascular Sciences
Professor of Functional Genomics

Contact details

Address
Institute of Cardiovascular Sciences
Institute for Biomedical Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham, B15 2TT

Roy Bicknell originally read chemistry at St. John's College, University of Oxford before studying for a doctorate in The William Dunn School of Pathology, University of Oxford as an E.P.Abraham scholar. He then won a NATO Postdoctoral Fellowship to study at Harvard Medical School. His original research interest was bacterial resistance to antibiotics but at Harvard moved to growth and angiogenic factors. He has published over 300 papers in the field of angiogenesis, has an H-index of 68 (Research Gate) and is recognised as an international expert in the field. 

Qualifications

  • Fellow of the Royal Society of Biology
  • D. Phil Pathology, 1984
  • MA Chemistry St. John's College, University of Oxford, 1984
  • BA Chemistry St. John's College, University of Oxford, 1980

Biography

Roy's interest were always in biology although he originally read chemistry as a sound knowledge of chemistry is a good grounding for biochemical research. For his PhD he chose to look at bacterial resistance to beta-lactam antibiotics. In that time he characterised two metallo beta-lactamases and studied their mechanism of action using cryoenzymology. On completion of his PhD he studied the mechanism of the zinc metalloenzyme  angiotensin converting enzyme  (ACE) with Bert Vallee at Harvard Medical School. It was during this time that the ACE inhibitors captopril and enalopril were discovered and high blood pressure ceased to be a major clinical problem. At the time Vallee and Folkman were trying to isolate a putative angiogenic factor and because of his protein expertise he asked Vallee if he could join the team. Angiogenesis was to be his main interest for the next 30 years and remains so today.

In 1989 he moved back to Oxford to set up the Angiogenesis Group of the Imperial Cancer Research Fund in the newly built Institute of Molecular Medicine.  Roy's work involved many studies on the newly identified vascular endothelial growth factor (VEGF) as well as other angiogenic factors. He was awarded tenure in 2004. These years led to some of his most highly cited papers including one that has over a thousand citations. That work showed that nitric oxide is essential for VEGF but not fibroblast growth factor induced angiogenesis. For the first time we realised that there is not just one mechanism of angiogenesis. With the rise of genomics Roy became interested in the identification of new endothelial genes. The first was delta-like 4 that was independently identified by three groups (one being led by a former PhD student of his). Later came Robo4 that he worked on for several years. Robo4 is the only endothelial specific roundabout gene and was an interesting finding for it showed that all four of the known neuronal guidance pathways have homologues in the endothelial cell involved in angiogenesis. In 2004 he was appointed Professor of Cancer Cell Biology in Oxford.

In 2005 Roy was recruited to Birmingham and started a five-year Cancer Research UK programme working together with Victoria Heath. They were still interested in novel endothelial genes but focussed on finding those that had potential as targets in tumour vessels. This led to the discovery of C-type lectin 14A (CLEC14A). CLEC14A expression is regulated by shear stress. Low shear stress induces expression and this leads to significantly higher expression in tumour vessels (due to poor blood flow) than in those in healthy tissues. Our work on CLEC14A has taken two paths. The first is to understand its function and the second is to develop it as a target. It is clearly involved in angiogenesis and we recently characterised the interaction with its ligand multimerin-2 (MMRN2) and showed that it forms a 'supercomplex' in which multimerin2 also binds the related endosialin and CD93. We plan now to study the functional consequences and interactions of this complex. For targeting they work with Steve Lee on CAR modified T cells (funded by the cell therapy catapult) and with several companies on antibody drug conjugates. Our final interest is in developing vaccines that target the tumour vasculature.

Teaching

  • Lectures and small group teaching for cancer and cardiovascular science to MBChB and Biomedical Sciences.
  • Lectures in BMedSci year 3 modules in cancer, vascular biology and inflammation.
  • Lectures on multiple MRes and MSc courses.

Postgraduate supervision

Roy has successfully supervised 45 PhD students to date. He currently supervises 6 students but is actively looking for new students. He is particularly interested in supervising doctoral research students in the following areas:

Elucidating the mechanisms by which multimerin-2 and it ligands CLEC14A, CD93 and endosialin mediate angiogenesis. We would like to focus on the extracellular protein interactions and intracellular signalling.

Development of a cancer vaccine using conjugate proteins.

Study of MCAM and its role in renal cancer. Use as a vascular target in mouse models of cancer.

Research

Research Themes

  • Angiogenesis
  • Endothelial biology and vascular targeting of anti-cancer therapies
  • Cell surface receptors and Imaging
  • Targeted therapies including CAR modified T cells, antibody drug conjugates and vaccines

Our research focuses on the endothelial cell and endothelial genes that act either as targets or play a role in angiogenesis. We are particularly interested in the type 14 family of C-type lectins that includes CLEC14A, CD93 and endosialin and their common ligand multimerin-2. We are also interested in MCAM as a target in renal cancer and von Hippel Lindau induced renal cancer. We use a wide variety  of techniques from basic cell and molecular biology through to animal models of cancer and mouse transgenesis.

Other activities

  • Editorial Board of Angiogenesis (1997-)
  • External examiner, Sheffield Medical School (2015-)
  • Consultant to five Pharma companies
  • Scientific founder of Cytox and Chimeric Therapeutics

Publications

Khan KA, Naylor AJ, Khan A, Noy PJ, Mambretti M, Lodhia P, Athwal J, Korzystka A, Buckley CD, Willcox BE, Mohammed F and Bicknell R. (2017) Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface. Oncogene, E-pub Jul 3.

Wragg JW, Heath VL and Bicknell R. (2017) Sunitinib treatment enhances metastasis of innately drug-resistant breast tumors. Cancer Res. 77(4):1008-1020

Ferguson HJ, Wragg JW, Ward S, Heath VL, Ismail T and Bicknell R. (2016) Glutamate dependent NMDA receptor 2D is a novel angiogenic tumour endothelial marker in colorectal cancer. Oncotarget. 7(15):20440-54

Noy PJ, Swain RK, Khan K, Lodhia P and Bicknell R. (2016) Sprouting angiogenesis is regulated by shedding of the C-type lectin family 14, member A (CLEC14A) ectodomain, catalyzed by rhomboid-like 2 protein (RHBDL2). FASEB J. 30(6):2311-23.

Wragg JW, Finnity JP, Anderson JA, Ferguson HJ, Porfiri E, Bhatt RI, Murray PG, Heath VL and Bicknell R. (2016) MCAM and LAMA4 are highly enriched in tumor blood vessels of renal cell carcinoma and predict patient outcome. Cancer Res. 76(8):2314-26.

Noy PJ, Lodhia P, Khan K, Zhuang X, Ward DG, Verissimo AR, Bacon A and Bicknell R. (2015) Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth. Oncogene. 34(47):5821-31

Zhuang X, Herbert JM, Lodhia P, Bradford J, Turner AM, Newby PM, Thickett D, Naidu U, Blakey D, Barry S, Cross DA and Bicknell R. (2015) Identification of novel vascular targets in lung cancer. Br J Cancer. 112(3):485-94

Zhuang X, Ahmed F, Zhang Y, Ferguson HJ, Steele JC, Steven NM, Nagy Z, Heath VL, Toellner KM and Bicknell R. (2015) Robo4 vaccines induce antibodies that retard tumor growth. Angiogenesis. 18(1):83-95

Mura M, Swain RK, Zhuang X, Vorschmitt H, Reynolds G, Durant S, Beesley JF, Herbert JM, Sheldon H, Andre M, Sanderson S, Glen K, Luu NT, McGettrick HM, Antczak P, Falciani F, Nash GB, Nagy ZS and Bicknell R. (2012) Identification and angiogenic role of the novel tumor endothelial marker CLEC14A. Oncogene. 31(3):293-305 

Expertise

Development of anti-cancer strategies by targeting the tumour blood vessels; development of anti-cancer drugs

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