Yr Athro Dipak Ramji
Reader
- Email:
- ramji@cardiff.ac.uk
- Telephone:
- +44 (0)29 2087 6753
- Fax:
- +44 (0)29 2087 4116
- Location:
- Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
- Ar gael fel goruchwyliwr ôl-raddedig
Research overview
The overall aim of research in my laboratory is to understand comprehensively how specific factors, such as cytokines and lipid metabolites, regulate gene expression during health and disease. In particular, we are elucidating the pathways leading from the interaction of such factors with their receptors, through the intracellular signalling cascades, to the control of gene expression in the nucleus. Specific focus is on cytokine signalling and gene expression, particularly in macrophages, in inflammatory disorders such as atherosclerosis, with the longer-term goal of identifying new therapeutic/preventative targets/avenues. Previous and current research has been funded by grants from the Wellcome Trust, BBSRC, British Heart Foundation, MRC and GlaxoSmithKline.
Research division
I did my BSc in Biochemistry and PhD on Dictyostelium development at The University of Leeds. This was followed by postdoctoral research at the European Molecular Biology Laboratories (Heidelberg) and Istituto di Ricerche di Biologia Molecolare "P. Angeletti" (Rome) on the molecular mechanisms underlying liver-specific gene expression during inflammation. I was a recipient of fellowships from the Royal Society, EMBL, University of Rome and the EU. I moved to Cardiff University as a Lecturer in August 1992. I was promoted to a Senior Lecturer in 2003 and to a Reader in 2006.
2019
- Gallagher, H.et al. 2019. Dihimo-γ-linolenic acid inhibits several key cellular processes associated with atherosclerosis. BBA - Molecular Basis of Disease 1865(9), pp. 2538-2550. (10.1016/j.bbadis.2019.06.011)
- Buckley, M. L.et al. 2019. The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways. Scientific Reports 9, article number: 11317. (10.1038/s41598-019-47620-8)
- Ramji, D. P. 2019. Polyunsaturated fatty acids and atherosclerosis: insights from pre-clinical studies. European Journal of Lipid Science and Technology 121(1), article number: 1800029. (10.1002/ejlt.201800029)
2018
- Moss, J., Williams, J. and Ramji, D. 2018. Nutraceuticals as therapeutic agents for atherosclerosis. Biochimica et Biophysica Acta - Molecular Basis of Disease 1864(5. A.), pp. 1562-1572. (10.1016/j.bbadis.2018.02.006)
2017
- Moss, J. and Ramji, D. 2017. Cytokines in Atherosclerosis. In: Foti, M. and Locati, M. eds. Cytokine Effector Functions in Tissues.. Academic Press, pp. 109-118.
- Gallagher, H.et al. 2017. Nutraceuticals in the prevention and treatment of Atherosclerosis. Cardiology 137(S1), pp. 264. (10.1159/000477751)
- Michael, D. R.et al. 2017. The anti-cholesterolaemic effect of a consortium of probiotics: an acute study in C57BL/6J mice. Scientific Reports 7(1), article number: 2883i. (10.1038/s41598-017-02889-5)
2016
- Salter, R. C.et al. 2016. The role of mitogen-activated protein kinases and sterol receptor coactivator-1 in TGF-β-regulated expression of genes implicated in macrophage cholesterol uptake. Scientific Reports 6, article number: 34368. (10.1038/srep34368)
- Moss, J. W. E. and Ramji, D. P. 2016. Nutraceutical therapies for atherosclerosis. Nature Reviews Cardiology 13(9), pp. 513-532. (10.1038/nrcardio.2016.103)
- Moss, J. and Ramji, D. P. 2016. Cytokines: roles in atherosclerosis disease progression and potential therapeutic targets. Future Medicinal Chemistry 8(11), pp. 1317-1330. (10.4155/fmc-2016-0072)
- Davies, T.et al. 2016. The action of Nutraceuticals on key macrophage processes associated with Atherosclerosis. Cardiology 134(S1), pp. 314-314. (10.1159/000447505)
- Ramji, D.et al. 2016. Cytkines in atherosclerosis: molecular mechanisms underlying their actions and promising therapeutic targets. Journal of Clinical and Experimental Cardiology 7(6), pp. 52-52.
- Ramji, D.et al. 2016. Nutraceuticals as preventative and therapeutic agents in atherosclerosis. Journal of Clinical and Experimental Cardiology 7(6), pp. 31-31. (10.4172/2155-9880.C1.029)
- Michael, D. R.et al. 2016. Lactobacillus plantarum CUL66 can impact cholesterol homeostasis in Caco-2 enterocytes. Beneficial Microbes 7(3), pp. 443-451. (10.3920/BM2015.0146)
- Moss, J. W. E.et al. 2016. A unique combination of nutritionally active ingredients can prevent several key processes associated with atherosclerosis in vitro. PLoS ONE 11(3), article number: e0151057. (10.1371/journal.pone.0151057)
2015
- Ramji, D. P. and Davies, T. S. 2015. Cytokines in atherosclerosis: key players in all stages of disease and promising therapeutic targets. Cytokine & Growth Factor Reviews 26(6), pp. 673-685. (10.1016/j.cytogfr.2015.04.003)
- Huwait, E. A.et al. 2015. Protein Kinase C is involved in the induction of ATP-Binding cassette transporter A1 expression by liver X receptor/retinoid X receptor agonist in human macrophages. Journal of Cellular Biochemistry 116(9), pp. 2032-2038. (10.1002/jcb.25157)
- Moss, J. and Ramji, D. P. 2015. Interferon-γ: Promising therapeutic target in atherosclerosis. World Journal of Experimental Medicine 5(3), pp. 154-159. (10.5493/wjem.v5.i3.154)
- Buckley, M. and Ramji, D. P. 2015. The influence of dysfunctional signaling and lipid homeostasis in mediating the inflammatory responses during atherosclerosis. Biochimica et Biophysica Acta - Molecular Basis of Disease 1852(7), pp. 1498-1510. (10.1016/j.bbadis.2015.04.011)
- Michael, D. R.et al. 2015. The phosphoinositide 3-kinase signaling pathway is involved in the control of modified low-density lipoprotein uptake by human macrophages. Lipids 50(3), pp. 253-260. (10.1007/s11745-015-3993-0)
- Davies, T. S.et al. 2015. Interferon gamma signalling in atherosclerosis: pro-atherogenic actions and therapeutic approaches. Cardiology 131, pp. 292-292.
2014
- Willis, G. R.et al. 2014. Young women with polycystic ovary syndrome have raised levels of circulating annexin V-positive platelet microparticles. Human Reproduction 29(12), pp. 2756-2769. (10.1093/humrep/deu281)
- Davies, T. S.et al. 2014. Pro- therogenic actions of interferon-gamma on macrophages in atherosclerosis. Cardiology 128(S1), pp. 278-278. (10.1159/000365062)
- Ashlin, T. G.et al. 2014. The anti-atherogenic cytokine interleukin-33 inhibits the expression of a disintegrin and metalloproteinase with thrombospondin motifs-1,-4 and-5 in human macrophages: Requirement of extracellular signal-regulated kinase, c-Jun N-terminal kinase and phosphoinositide 3-kinase signaling pathways. The International Journal of Biochemistry & Cell Biology 46, pp. 113-123. (10.1016/j.biocel.2013.11.008)
2013
- Michael, D. R.et al. 2013. Differential regulation of macropinocytosis in macrophages by cytokines: Implications for foam cell formation and atherosclerosis. Cytokine 64(1), pp. 357-361. (10.1016/j.cyto.2013.05.016)
- Ashlin, T. G., Kwan, A. P. L. and Ramji, D. P. 2013. Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17. Cytokine 64(1), pp. 234-242. (10.1016/j.cyto.2013.06.315)
2012
- Michael, D. R., Salter, R. C. and Ramji, D. P. 2012. TGF-β inhibits the uptake of modified low density lipoprotein by human macrophages through a Smad-dependent pathway: A dominant role for Smad-2. Biochimica et Biophysica Acta - Molecular Basis of Disease 1822(10), pp. 1608-1616. (10.1016/j.bbadis.2012.06.002)
- Michael, D. R.et al. 2012. Liver X receptors, atherosclerosis and inflammation. Current Atherosclerosis Reports 14(3), pp. 284-293. (10.1007/s11883-012-0239-y)
- Michael, D. R.et al. 2012. Macrophages, lipid metabolism and gene expression in atherogenesis: a therapeutic target of the future?. Clinical Lipidology 7(1), pp. 37-48. (10.2217/clp.11.73)
2011
- McLaren, J. E.et al. 2011. Eicosapentaenoic acid and docosahexaenoic acid regulate modified LDL uptake and macropinocytosis in human macrophages. Lipids 46(11), pp. 1053-1061.
- McLaren, J. E.et al. 2011. Cytokines, macrophage lipid metabolism and foam cells: implications for cardiovascular disease therapy. Progress in Lipid Research 50(4), pp. 331-347. (10.1016/j.plipres.2011.04.002)
- Salter, R.et al. 2011. The expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 in human macrophages is inhibited by the anti-atherogenic cytokine transforming growth factor-β and requires Smads, p38 mitogen-activated protein kinase and c-Jun. The International Journal of Biochemistry & Cell Biology 43(5), pp. 805-811. (10.1016/j.biocel.2011.02.005)
- Huwait, E.et al. 2011. A novel role for c-Jun N-terminal kinase and phosphoinositide 3-kinase in the liver X receptor-mediated induction of macrophage gene expression. Cellular Signalling 23(3), pp. 542-549. (10.1016/j.cellsig.2010.11.002)
- Li, N., Salter, R. C. and Ramji, D. P. 2011. Molecular mechanisms underlying the inhibition of IFN-γ-induced, STAT1-mediated gene transcription in human macrophages by simvastatin and agonists of PPARs and LXRs. Journal of Cellular Biochemistry 112(2), pp. 675-683. (10.1002/jcb.22976)
2010
- McLaren, J. E.et al. 2010. In vitro promotion of macrophage foam cell formation by Death Receptor 3 and its ligand TL1A. Immunology 131(1), pp. 103-103.
- Li, N.et al. 2010. ERK is integral to the IFN-γ-mediated activation of STAT1, the expression of key genes implicated in atherosclerosis, and the uptake of modified lipoproteins by human macrophages. The Journal of Immunology 185(5), pp. 3041-3048. (10.4049/jimmunol.1000993)
- McLaren, J. E.et al. 2010. IL-33 reduces macrophage foam cell formation. The Journal of Immunology 185(2), pp. 1222-1229. (10.4049/jimmunol.1000520)
- McLaren, J. E.et al. 2010. The TNF-like protein 1A-death receptor 3 pathway promotes macrophage foam cell formation in vitro. Journal of Immunology 184(10), pp. 5827-5834. (10.4049/jimmunol.0903782)
- Salter, R. C.et al. 2010. ADAMTS proteases: key roles in atherosclerosis?. Journal of Molecular Medicine 88(12), pp. 1203-1211. (10.1007/s00109-010-0654-x)
- Ali, S.et al. 2010. Requirement for nuclear factor kappa B signalling in the interleukin-1-induced expression of the CCAAT/enhancer binding protein-delta gene in hepatocytes. International Journal of Biochemistry & Cell Biology 42(1), pp. 113-119. (10.1016/j.biocel.2009.09.018)
2009
- McLaren, J. E. and Ramji, D. 2009. Interferon gamma: A master regulator of atherosclerosis. Cytokine & Growth Factor Reviews 20(2), pp. 125-135. (10.1016/j.cytogfr.2008.11.003)
- McLaren, J. E. and Ramji, D. P. 2009. Interferon gamma: A master regulator of atherosclerosis. Cytokine & Growth Factor Reviews 20(2), pp. 125-135. (10.1016/j.cytogfr.2008.11.003)
- Ramji, D. P. 2009. Growth hormone-releasing peptides, CD36, and stimulation of cholesterol efflux: cyclooxygenase-2 is the link. Cardiovascular Research 83(3), pp. 419-420. (10.1093/cvr/cvp195)
- Foka, P.et al. 2009. The tumour necrosis factor-a-mediated suppression of the CCAAT/enhancer binding protein-a gene transcription in hepatocytes involves inhibition of autoregulation. International Journal of Biochemistry & Cell Biology 41(5), pp. 1189-1197. (10.1016/j.biocel.2008.10.024)
2008
- Singh, N. N., Salter, R. C. and Ramji, D. P. 2008. Molecular mechanisms underlying transforming growth factor-beta-induced expression of the apolipoprotein E gene [Abstract]. Atherosclerosis Supplements 9(1), pp. 21. (10.1016/S1567-5688(08)70078-3)
- Ramji, D. P.et al. 2008. Cytokine signalling in macrophages and the expression of key genes implicated in atherosclerosis [Abstract]. Atherosclerosis Supplements 9(1), pp. 53. (10.1016/S1567-5688(08)70209-5)
- Harris, S. M.et al. 2008. The interferon-γ-mediated inhibition of lipoprotein lipase gene transcription in macrophages involves casein kinase 2- and phosphoinositide-3-kinase-mediated regulation of transcription factors Sp1 and Sp3. Cellular Signalling 20(12), pp. 2296-2301. (10.1016/j.cellsig.2008.08.016)
- Singh, N. N. and Ramji, D. P. 2008. Protein kinase CK2, an important regulator of the inflammatory response?. Journal of Molecular Medicine 86(8), pp. 887-897. (10.1007/s00109-008-0352-0)
2007
- Singh, N. N.et al. 2007. Signaling pathways underlying cytokine regulated expression of key genes in macrophages implicated in atherosclerosis. Atherosclerosis Supplements 8(1), pp. 4-4.
- Harvey, E. J., Li, N. and Ramji, D. . P. 2007. Critical role for casein kinase 2 and phosphoinositide-3-kinase in the interferon- -induced expression of monocyte chemoattractant protein-1 and other key genes implicated in atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology 27(4), pp. 806-812. (10.1161/01.ATV.0000258867.79411.96)
2006
- Monslow, J.et al. 2006. Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene. The Journal of Biological Chemistry 281(26), pp. 18043-18050. (10.1074/jbc.M510467200)
- Foka, P.et al. 2006. Signalling pathways underlying transforming growth factor-beta regulated expression of key genes implicated in the control of foam cell formation. Atherosclerosis Supplements 7(3), pp. 237-237.
- Kockar, F., Yildirim, H. and Ramji, D. P. 2006. Molecular characterisation and comparative analysis of the human C/EBP delta promoter to mammalian homologues. FEBS Letters 273, pp. 334-334.
- Singh, N. N. and Ramji, D. P. 2006. The role of transforming growth factor-β in atherosclerosis. Cytokine & Growth Factor Reviews 17(6), pp. 487-499. (10.1016/j.cytogfr.2006.09.002)
- Singh, N. N.et al. 2006. Transforming growth factor-b-regulated expression of genes in macrophages implicated in the control of cholesterol homoeostasis. Biochemical Society Transactions 34(6), pp. 1141-1141. (10.1042/BST0341141)
- Singh, N. N. and Ramji, D. P. 2006. Transforming growth factor-β-induced expression of the apolipoprotein e gene requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2. Arteriosclerosis Thrombosis and Vascular Biology 26(6), pp. 1323-1329. (10.1161/01.ATV.0000220383.19192.55)
- Irvine, S. A.et al. 2006. Lipoprotein lipase is expressed by glomerular mesangial cells. The International Journal of Biochemistry & Cell Biology 38(1), pp. 12-16. (10.1016/j.biocel.2005.07.008)
2005
- Harvey, E. J. and Ramji, D. P. 2005. Up-regulation of monocyte chemoattractant protein-1 and the monocyte chemoattractant protein-1 receptor (CCR2) in macrophages by the pro-inflammatory cytokine interferon-gamma. Arteriosclerosis Thrombosis and Vascular Biology 25(5), pp. E64-E64.
- Foka, P.et al. 2005. Molecular mechanisms involved in the cytokine-regulated expression of genes in macrophages implicated in foam cell formation and atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology 25(5), pp. E71-E71.
- Irvine, S. A.et al. 2005. A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages. Nucleic Acids Research, pp. 1423-1434. (10.1093/nar/gki280)
- Harvey, E. J. and Ramji, D. P. 2005. Interferon-γ and atherosclerosis: pro- or anti-atherogenic?. Cardiovascular Research 67(1), pp. 11-20. (10.1016/j.cardiores.2005.04.019)
- Greenow, K., Pearce, N. J. and Ramji, D. . P. 2005. The key role of apolipoprotein E in atherosclerosis. Journal of Molecular Medicine 83(5), pp. 329-342. (10.1007/s00109-004-0631-3)
2004
- Greenow, K. R., Pearce, N. and Ramji, D. P. 2004. A critical role for the phosphoinositide-3-kinase signal transduction pathway in the activation of apolipoprotein E gene expression. Atherosclerosis Supplements 5(1), pp. 25-25. (10.1016/S1567-5688(04)90110-4)
- Foka, P., Irvine, S. and Ramji, D. P. 2004. Regulation of CCAAT/enhancer binding protein-alpha gene transcription by interleukin-6. Atherosclerosis Supplements 5(1), pp. 31-31.
- Irvine, S. A., Foka, P. and Ramji, D. P. 2004. Transcriptional regulation of macrophage lipoprotein lipase gene expression by transforming growth factor-beta. Atherosclerosis Supplements 5(1), pp. 31-32. (10.1016/S1567-5688(04)90137-2)
- Ramji, D. P.et al. 2004. Signal transduction pathways and transcriptional control mechanisms involved in the cytokine-mediated, regulation of key genes in macrophages implicated in foam cell formation and atherosclerosis. Atherosclerosis Supplements 5(1), pp. 29-30.
2003
- Foka, P.et al. 2003. Interleukin-6 represses the transcription of the CCAAT/enhancer binding protein-α in hepatoma cells by inhibiting its ability to autoactivate the proximal promoter region. Nucleic Acids Research, pp. 6722-6732. (10.1093/nar/gkg861)
- Ramji, D. P.et al. 2003. Novel pathways for cytokine-mediated regulation of macrophage lipoprotein lipase gene expression. Atherosclerosis Supplements 4(2), pp. 62-62. (10.1016/S1567-5688(03)90263-7)
- Mead, J. R.et al. 2003. Interferon-γ stimulates the expression of the inducible cAMP early repressor in macrophages through the activation of casein kinase 2: A Potentially novel pathway for interferon-γ-mediated inhibition of gene transcription. Journal of Biological Chemistry, pp. 17741-17751. (10.1074/jbc.M301602200)
2002
- Ramji, D. P. and Foka, P. 2002. CCAAT/Enhancer binding proteins: structure, function and regulation. Biochemical Journal 365, pp. 561-575. (10.1042/BJ20020508)
- Mead, J. R. and Ramji, D. P. 2002. The pivotal role of lipoprotein lipase in atherosclerosis. Cardiovascular Research 55(2), pp. 261-269. (10.1016/S0008-6363(02)00405-4)
- Hughes, T. R.et al. 2002. A novel role of Sp1 and Sp3 in the interferon- -mediated suppression of macrophage lipoprotein lipase gene transcription. Journal of Biological Chemistry 277(13), pp. 11097-11106. (10.1074/jbc.M106774200)
- Mead, J., Irvine, S. and Ramji, D. P. 2002. Lipoprotein lipase: structure, function, regulation, and role in disease. Journal of Molecular Medicine 80(12), pp. 753-769. (10.1007/s00109-002-0384-9)
2001
- Kockar, F. T.et al. 2001. Analysis of the Xenopus laevis CCAAT-enhancer binding protein α gene promoter demonstrates species-specific differences in the mechanisms for both auto-activation and regulation by Sp1. Nucleic Acids Research 29(2), pp. 362-372. (10.1093/nar/29.2.362)
- Foka, P., Kousteni, S. and Ramji, D. P. 2001. Molecular characterization of the xenopus CCAAT-enhancer binding protein β gene promoter. Biochemical and Biophysical Research Communications 285(2), pp. 430-436. (10.1006/bbrc.2001.5203)
2000
- Tengku-Muhammad, T. S.et al. 2000. Differential regulation of macrophage ccaat- enhancer binding protein isoforms by lipopolysaccharide and cytokines. Cytokine 12(9), pp. 1430-1436. (10.1006/cyto.2000.0711)
- Granger, R. L., Hughes, T. R. and Ramji, D. P. 2000. Gene, stimulus and cell-type specific regulation of activator protein-1 in mesangial cells by lipopolysaccharide and cytokines. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1492(1), pp. 100-107. (10.1016/S0167-4781(00)00089-0)
- Tengku-Muhammad, T. S.et al. 2000. Cytokine-mediated differential regulation of macrophage activator protein-1 genes. Cytokine 12(6), pp. 720-726. (10.1006/cyto.1999.0620)
- Granger, R. L., Hughes, T. R. and Ramji, D. P. 2000. Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines. Biochimica et Biophysica Acta - Molecular Basis of Disease 1501(2-3), pp. 171-179. (10.1016/S0925-4439(00)00016-8)
- Davies, G. E.et al. 2000. The ovine CCAAT-enhancer binding protein δ gene: cloning, characterization, and species-specific autoregulation. Biochemical and Biophysical Research Communications 271(2), pp. 346-352. (10.1006/bbrc.2000.2630)
1999
- Mead, J. R., Cryer, A. and Ramji, D. P. 1999. Lipoprotein lipase, a key role in atherosclerosis?. FEBS Letters 462(1-2), pp. 1-6. (10.1016/S0014-5793(99)01495-7)
- Kousteni, S., Tura-Kockar, F. and Ramji, D. P. 1999. Sequence and expression analysis of a novel Xenopus laevis cDNA that encodes a protein similar to bacterial and chloroplast ribosomal protein L24. Gene 235(1-2), pp. 13-18. (10.1016/S0378-1119(99)00221-8)
- Tengku-Muhammad, T. S.et al. 1999. Involvement of both the tyrosine kinase and the phosphatidylinositol-3 ' kinase signal transduction pathways in the regulation of lipoprotein lipase expression in J774.2 macrophages by cytokines and lipopolysaccharide. Cytokine 11(7), pp. 463-468. (10.1006/cyto.1998.0460)
- Tengku-Muhammad, T. S.et al. 1999. Synergism between lipopolysaccharide and interferon gamma in the regulation of lipoprotein lipase in macrophages. Cytokine 11(6), pp. 408-415. (10.1006/cyto.1998.0447)
1998
- Sabatakos, G.et al. 1998. Rapid communication: Nucleotide sequence of ovine C/EBP epsilon gene. Journal of Animal Science 76(11), pp. 2953-2954.
- Kousteni, S.et al. 1998. Characterisation and developmental regulation of the Xenopus laevis CCAAT-enhancer binding protein β gene. Mechanisms of Development 77(2), pp. 143-148. (10.1016/S0925-4773(98)00128-2)
1997
- Kousteni, S.et al. 1997. Sequence and expression analysis of a Xenopus laevis cDNA which encodes a homologue of mammalian 14-3-3 zeta protein. Gene 190(2), pp. 279-285. (10.1016/S0378-1119(97)00013-9)
The overall aim of research in my laboratory is to understand comprehensively how specific factors, such as cytokines and lipid metabolites, regulate gene expression during health and disease. In particular, we are elucidating the pathways leading from the interaction of such factors with their receptors, through the intracellular signalling cascades, to the control of gene expression in the nucleus. Specific focus is on cytokine signalling and gene expression, particularly in macrophages, in inflammatory disorders such as atherosclerosis, with the longer-term goal of identifying new therapeutic/preventative targets/avenues. Previous and current research has been funded by grants from the Wellcome Trust, BBSRC, British Heart Foundation, MRC and GlaxoSmithKline. Our research is focused on two major areas:
Regulation of macrophage gene expression during atherosclerosis
Atherosclerosis and its complications, such as coronary heart disease and stroke, are directly responsible for about 34% of all deaths in the Western world. Atherosclerosis is an inflammatory disorder of the vasculature orchestrated by cytokines. Macrophages play a prominent role in the pathogenesis of this disease, with the uncontrolled uptake of atherogenic lipoproteins by these cells and the subsequent transformation into foam cells representing a critical early step in atherogenesis. The products of several genes contribute, either directly or indirectly, to the inflammatory response, lipoprotein metabolism and foam cell formation. The regulation of such genes by factors that are known to be present in the atherosclerotic lesion, such as cytokines, growth factors, chemotactic factors and modified lipoproteins is, therefore, likely to make a major contribution to the initiation and the progression of the disease. A major focus of research in my laboratory is devoted to understanding the molecular mechanisms by which such factors, particularly cytokines, regulate the inflammatory response, foam cell formation and the expression of key genes implicated in these processes. Specific focus is on the actions of interferon-gamma, transforming growth factor-beta and interleukin-33. In addition, the mechanisms underlying the anti-inflammatory actions of drugs (e.g. statins, activators of nuclear receptors) and fatty acids/metabolites (e.g. dihomo-gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid) are being elucidated. Such studies will advance our understanding of the molecular basis of foam cell formation and atherosclerosis and, in the longer term, identify potentially novel targets for therapeutic intervention.
Regulation of transcription factors belonging to the CCAAT/enhancer binding protein (C/EBP) family
The C/EBP family plays a key role in the control of cellular growth and differentiation, and the pathogenesis of several diseases. The regulation of these factors during both physiological and pathophysiological conditions has hitherto been poorly understood. The regulation of the C/EBP family during inflammation in the liver was the focus of my post-doctoral research and has been continued at Cardiff. In addition, several projects have been initiated to delineate the mechanisms by which cytokines regulate the expression of the C/EBP family during a number of other inflammatory conditions.
Grants
- Wellcome Trust
- British Heart Foundation
- GlaxoSmithKline
- BBSRC
- MRC
Collaborations
- Prof. Foo Liew (FRS), University of Glasgow
- Prof. Thomas Decker, Max F. Perutz Laboratories, Vienna
- Prof. Masato Ogata, Mie University Graduate School of Medicine
- Drs Jacques Pouysségur and Giles Pàges, University of Nice
- Prof. Sammy Boussiba and Dr. Inna Khozin-Goldberg, Ben-Gurion University
- Dr. Daryn Michael, Cultech Ltd
- Dr Jason Johnson (Bristol Heart Institute)
- Prof. Jonathan Napier and Dr. Olga Sayanova, Rothamsted Research
- Dr. Nigel Pearce, GlaxoSmithKline
- Prof. Gavin Wilkinson, and Drs Timothy Hughes, John Martin, Tim Bowen, Eddie Wang and Ian Humphreys, School of Medicine, Cardiff
- Prof. John Harwood and Drs Alvin Kwan and Irina Guschina, School of Biosciences, Cardiff