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David Leake

Email:
d.s.leake@reading.ac.uk
Phone:
+44 (0) 118 378 7062
Job title:
Professor

Responsibilities:

Management Committee of Institute for Cardiovascular and Metabolic Research

Areas of interest

Mechanisms of low density lipoprotein oxidation in atherosclerosis
Use of novel lysosomotropic antioxidant drugs to treat atherosclerosis
Atherogenic effects of low extracellular pH on cells found in atherosclerotic lesions

Postgraduate supervision

Study for a PhD with Professor David Leake

Low density lipoprotein oxidation and atherosclerosis

Teaching

Part 1: Pathology: Introduction to Human Disease; Biochemistry and Metabolism
Part 2: Pharmacology (module convenor); Clinical Biochemistry (module convenor)
Part 3: Cardiovascular Disease (module convenor); Medical Genetics

Research centres and groups

National Collaborators

Prof. Peter Weinberg, Imperial College London
Dr Grisha Pirianov, Anglia Ruskin University
Prof Ronit Shiri-Sverdlov, Maastricht University, The Netherlands
Dr Robin Poston, Queen Mary University of London

Awards and honours

Esteem Factors

External Examiner for MRes in Biomedical Science at St George's University of London
Selected as the 'Scientist of the week' by the Association for Eradication of Heart Attack, USA in July 2002 for 'pioneering work on the low pH of atherosclerotic lesions'.
Prize for the best research paper of the year in the Faculty of Life Sciences of the University of Reading in 2009 (for research paper Wen, Y. & Leake, D.S. (2007) Circ. Res. 100, 1337-1343. Low density lipoprotein undergoes oxidation within lysosomes in cells)

Professional bodies/affiliations

Funding from British Heart Foundation

Impact, enterprise and outreach

Patent taken out for the change of use of an antioxidant lysosomotropic drug that inhibits atherosclerosis to treat coronary heart disease, strokes and peripheral artery disease
Advice on careers in biomedical sciences at Reading School Careers Conference
Highly commended image in the British Heart Foundation annual image competition (featured on websites of the BBC, Independent, Guardian and Daily Mail)

Publications

Poston, R. , Chughtai, J. , Ujkaj, D. , Louis, H. , Leake, D. , Cooper, D. (2022) Monocytic cell adhesion to oxidised ligands: relevance to cardiovascular disease. Biomedicines , 10 (12). ISSN: 2227-9059 | doi: https://dx.doi.org/10.3390/biomedicines10123083
Ojo, O. and Leake, D. (2022) Effects of lysosomal low density lipoprotein oxidation by ferritin on macrophage function. Free Radical Research ISSN: 1071-5762 | doi: https://dx.doi.org/10.1080/10715762.2022.2133703

Ojo, O. and Leake, D. (2021) Vitamins E and C do not effectively inhibit low density lipoprotein oxidation by ferritin at lysosomal pH. Free Radical Research ISSN: 1071-5762 | doi: https://dx.doi.org/10.1080/10715762.2021.1964494
Houben, T. , Yadati, T. , De Kruijf, R. , Gijbels, M. , Luiken, J. , Van Zandvoort, M. , Kapsokalyvas, D. , Lütjohann, D. , Westerterp, M. , Plat, J. , Leake, D. , Shiri-Sverdlov, R. (2021) Pro-inflammatory implications of 2-hydroxypropyl-β-cyclodextrin treatment. Frontiers in Immunology , 12 ISSN: 1664-3224 | doi: https://dx.doi.org/10.3389/fimmu.2021.716357
Ahmad, F. , Mitchell, R. , Houben, T. , Palo, A. , Yasdati, T. , Parnell, A. , Patel, K. , Shiri-Sverdlov, R. , Leake, D. (2021) Cysteamine decreases low density lipoprotein oxidation, causes regression of atherosclerosis and improves liver and muscle function in LDL receptor deficient mice. JAHA: Journal of the American Heart Association ISSN: 2047-9980 | doi: https://dx.doi.org/10.1161/JAHA.120.017524

Alboaklah, H. and Leake, D. (2020) Effect of vitamin E on low density lipoprotein oxidation at lysosomal pH. Free Radical Research , 54 (8-9). pp. 574-584. ISSN: 1071-5762 | doi: https://dx.doi.org/10.1080/10715762.2020.1817912
Bhatti, S. , Leidi, A. , Leake, D. , Li, J. (2020) Studying biological science does not lead to adoption of a healthy lifestyle. Perspectives in Public Health , 140 (4). pp. 232-239. ISSN: 1757-9139 | doi: https://dx.doi.org/10.1177/1757913919890889

Wen, Y. , Ahmad, F. , Mohri, Z. , Weinberg, P. , Leake, D. (2019) Cysteamine inhibits lysosomal oxidation of low density lipoprotein in human macrophages and reduces atherosclerosis in mice. Atherosclerosis , 291 pp. 9-18. ISSN: 0021-9150 | doi: https://dx.doi.org/10.1016/j.atherosclerosis.2019.09.019
Ahmad, F. and Leake, D. (2019) Lysosomal oxidation of LDL alters lysosomal pH, induces senescence and increases secretion of pro-inflammatory cytokines in human macrophages. Journal of Lipid Research , 60 pp. 98-110. ISSN: 1539-7262 | doi: https://dx.doi.org/10.1194/jlr.M088245

Ojo, O. and Leake, D. (2018) Low density lipoprotein oxidation by ferritin at lysosomal pH. Chemistry and Physics of Lipids , 217 pp. 51-57. ISSN: 0009-3084 | doi: https://dx.doi.org/10.1016/j.chemphyslip.2018.09.016
Palmer, C. , Peri, F. , Neumann, F. , Ahmad, F. , Leake, D. , Pirianov, G. (2018) The synthetic glycolipid-based TLR4 antagonist FP7 negatively regulates in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling. Innate Immunity , 24 (7). pp. 411-421. ISSN: 1753-4267 | doi: https://dx.doi.org/10.1177/1753425918798904
Ahmad, F. and Leake, D. (2018) Antioxidants inhibit low density lipoprotein oxidation less at lysosomal pH: a possible explanation as to why the clinical trials of antioxidants might have failed. Chemistry and Physics of Lipids , 213 pp. 13-24. ISSN: 0009-3084 | doi: https://dx.doi.org/10.1016/j.chemphyslip.2018.03.001

Calabuig-Navarro, M. , Jackson, K. , Kemp, C. , Leake, D. , Walden, C. , Lovegrove, J. , Minihane, A. (2017) A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s. Scientific Reports , 7 ISSN: 2045-2322 | doi: https://dx.doi.org/10.1038/srep44119

Gerry, A. and Leake, D. (2014) Effect of low extracellular pH on NF-κB activation in macrophages. Atherosclerosis , 233 (2). pp. 537-544. ISSN: 0021-9150 | doi: https://dx.doi.org/10.1016/j.atherosclerosis.2014.01.014

Wraith, K. , Magwenzi, S. , Aburima, A. , Wen, Y. , Leake, D. , Naseem, K. (2013) Oxidised low-density lipoproteins induce rapid platelet activation and shape change through tyrosine kinase and Rho kinase-signaling pathways. Blood , 122 (4). pp. 580-589. ISSN: 0006-4971 | doi: https://dx.doi.org/10.1182/blood-2013-04-491688

Satchell, L. and Leake, D. (2012) Oxidation of low density lipoprotein by iron at lysosomal pH: implications for atherosclerosis. Biochemistry , 51 (18). pp. 3767-3775. ISSN: 0006-2960 | doi: https://dx.doi.org/10.1021/bi2017975

Gieseg, . , Leake, . , Flavall, . , Amit, . , Reid, . , Yang, . (2009) Macrophage antioxidant protection within atherosclerotic plaques. Frontiers in Bioscience , 1 (14). pp. 1230-1246. ISSN: 1093-9946 | doi: https://dx.doi.org/10.2741/3305

Gerry, A. and Leake, D. (2008) A moderate reduction in extracellular pH protects macrophages against apoptosis induced by oxidised low density lipoprotein. Journal of Lipid Research , 49 (4). pp. 782-789. ISSN: 1539-7262 | doi: https://dx.doi.org/10.1194/jlr.M700349-JLR200
Gomez-Ruiz, . , Ames, . , Leake, . (2008) Antioxidant activity and protective effects of green and dark coffee components against human low density lipoprotein oxidation. European Food Research and Technology , 227 (4). pp. 1017-1024. ISSN: 1438-2377 | doi: https://dx.doi.org/10.1007/s00217-007-0815-5
Gerry, . , Satchell, . , Leake, . (2008) A novel method for production of lipid hydroperoxide- or oxysterol-rich low-density lipoprotein. Atherosclerosis , 197 (2). pp. 579-587. ISSN: 0021-9150 | doi: https://dx.doi.org/10.1016/j.atherosclerosis.2007.08.026

Wong, . , Gerry, . , Putt, . , Roberts, . , Weinberg, . , Humphries, . , Leake, . , Talmud, . (2007) Common variants of apolipoprotein A-IV differ in their ability to inhibit low density lipoprotein oxidation. Atherosclerosis , 192 (2). pp. 266-274. ISSN: 0021-9150 | doi: https://dx.doi.org/10.1016/j.atherosclerosis.2006.07.017
Wen, . and Leake, . (2007) Low density lipoprotein undergoes oxidation within lysosomes in cells. Circulation Research , 100 (9). pp. 1337-1343. ISSN: 0009-7330 | doi: https://dx.doi.org/10.1161/circresaha.107.151704
Kappler, . , Gerry, . , Brown, . , Reid, . , Leake, . , Gieseg, . (2007) Aqueous peroxyl radical exposure to THP-1 cells causes glutathione loss followed by protein oxidation and cell death without increased caspase-3 activity. Biochimica Et Biophysica Acta-Molecular Cell Research , 1773 (6). pp. 945-953. ISSN: 0167-4889 | doi: https://dx.doi.org/10.1016/j.bbamcr.2007.04.001
Horsley, . , Burkitt, . , Jones, . , Patterson, . , Harris, . , Moss, . , del Rio, . , Leake, . (2007) Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions. Archives of Biochemistry and Biophysics , 465 (2). pp. 303-314. ISSN: 0003-9861 | doi: https://dx.doi.org/10.1016/j.abb.2007.07.005
Gomez-Ruiz, . , Leake, . , Ames, . (2007) In vitro antioxidant activity of coffee compounds and their metabolites. Journal of Agricultural and Food Chemistry , 55 (17). pp. 6962-6969. ISSN: 0021-8561 | doi: https://dx.doi.org/10.1021/jf0710985
Wen, Y. and Leake, D. (2007) Low density lipoprotein undergoes oxidation within lysosomes in cells. Circulation Research , 100 pp. 1337-1343. ISSN: 0009-7330 | doi: https://dx.doi.org/10.1161/CIRCRESAHA.107.151704

Jackson, K. , Maitin, V. , Leake, D. , Yaqoob, P. , Williams, C. (2006) Saturated fat-induced changes in S-f 60-400 particle composition reduces uptake of LDL by HepG2 cells. Journal of Lipid Research , 47 (2). pp. 393-403. ISSN: 0022-2275 | doi: https://dx.doi.org/10.1194/jlr.M500382-JLR200
Tricon, . , Burdge, . , Jones, . , Russell, . , El-Khazen, . , Moretti, . , Hall, . , Gerry, . , Leake, D. , Grimble, . , Williams, . , Calder, . , Yaqoob, . (2006) Effects of dairy products naturally enriched with cis-9,trans-11 conjugated linoleic acid on the blood lipid profile in healthy middle-aged men. American Journal of Clinical Nutrition , 83 (4). pp. 744-753. ISSN: 0002-9165
Harris, . , Mann, . , Ruiz, . , Mushtaq, . , Leake, . (2006) Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein. Archives of Biochemistry and Biophysics , 455 (1). pp. 68-76. ISSN: 0003-9861 | doi: https://dx.doi.org/10.1016/j.abb.2006.07.019

Anwar, . , Li, . , Leake, . , Ishii, . , Mann, . , Siow, . (2005) Induction of heme oxygenase 1 by moderately oxidized low-density lipoproteins in human vascular smooth muscle cells: role of mitogen-activated protein kinases and Nrf2. Free Radical Biology and Medicine , 39 (2). pp. 227-236. ISSN: 0891-5849 | doi: https://dx.doi.org/10.1016/j.freeradbiomed.2005.03.012

Ishii, . , Itoh, . , Ruiz, . , Leake, . , Unoki, . , Yamamoto, . , Mann, . (2004) Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages - Activation by oxidatively modified LDL and 4-hydroxynonenal. Circulation Research , 94 (5). pp. 609-616. ISSN: 0009-7330 | doi: https://dx.doi.org/10.1161/01.res.0000119171.44657.45
Anwar, . , Leake, . , Siow, . (2004) MAPK pathways mediate induction of heme oxygenase-1 and glutathione by moderately oxidized low density lipoproteins in vascular smooth muscle cells. Free Radical Biology and Medicine , 36 pp. S44-S44. ISSN: 0891-5849

Kavanagh, . , Symes, . , Renaudin, . , Nova, . , Mesa, . , Boukouvalas, . , Leake, D. , Yaqoob, P. (2003) Degree of oxidation of low density lipoprotein affects expression of CD36 and PPAR gamma, but not cytokine production, by human monocyte-macrophages. Atherosclerosis , 168 (2). pp. 271-282. ISSN: 0021-9150 | doi: https://dx.doi.org/10.1016/s0021-9150(03)00148-5
Talbot, . , del Rio, . , Leake, . , Weinberg, . (2003) Oxidation affects the flow-induced aggregation of low density lipoprotein and its inhibition by albumin. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids , 1634 (1-2). pp. 24-29. ISSN: 1388-1981 | doi: https://dx.doi.org/10.1016/j.bbalip.2003.08.002
Patterson, . , Horsley, . , Leake, . (2003) Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: important role of uric acid. Journal of Lipid Research , 44 (3). pp. 512-521. ISSN: 0022-2275 | doi: https://dx.doi.org/10.1194/jlr.M200407-JLR200
Patterson, . , Lamb, . , Leake, . (2003) Mechanisms by which cysteine can inhibit or promote the oxidation of low density lipoprotein by copper. Atherosclerosis , 169 (1). pp. 87-94. ISSN: 0021-9150 | doi: https://dx.doi.org/10.1016/s0021-9150(03)00154-0

Alderman, C. , Bunyard, P. , Chain, B. , Foreman, J. , Leake, D. , Katz, D. (2002) Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?. Cardiovascular Research , 55 (4). pp. 806-819. ISSN: 0008-6363 | doi: https://dx.doi.org/10.1016/S0008-6363(02)00447-9
Leigh-Firbank, E. , Minihane, A. , Leake, D. , Wright, J. , Murphy, M. , Griffin, B. , Williams, C. (2002) Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses. British Journal of Nutrition , 87 pp. 435-445. ISSN: 0007-1145 | doi: https://dx.doi.org/10.1079/BJN2002556