| Research at Medicine |
| Professor Levon Khachigian |
 | Phone: 02 9385 2537 |  |
| Email: |
| Qualifications: BSc, PhD, DSc UNSW |
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| School/Unit: |
| School of Medical Sciences
Centre for Vascular Research |
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| Broad Research Areas: | |
| Cancer / Oncology
Cell Biology and Gene Regulation
Pathology
Cardiology and Vascular Disease | |
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| Specific Research Keywords: | |
| Atherogenesis and Inflammation
Cardiology and Vascular Disease
Genetics
Signalling and Transcription
Molecular Mechanisms | |
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| Research Interests: | |
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Professor Khachigian is a molecular biologist with specific interests in transcription factors that control the expression of growth factor and cell cycle regulatory genes in vascular (endothelial and smooth muscle) cells, and in novel strategies exploiting this information in the development of interventional approaches to treat and/or prevent vascular occlusive and other proliferative disorders. Professor Khachigian's research group (comprising basic scientists and cardiologists) at the UNSW Centre for Vascular Research (SOMS, Department of Pathology) is focused on five principal areas of research: * Isolation and characterization of new genes induced or repressed by vascular cell injury * Mechanisms of signaling and transcriptional control in vascular endothelial cells and smooth muscle cells * Molecular control of vascular cell proliferation and apoptosis * DNAzymes, siRNA and modified antisense as molecular and therapeutic tools * Animal models of neointima formation, angiogenesis, tumor growth, myocardial ischemia, and inflammation.
If you are interested in joining the Khachigian lab, as a PhD student, postdoc or research assistant, please email your CV to L.Khachigian@unsw.edu.au. |
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| Teaching Interests: | |
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Molecular pathobiology
Molecular biology/transcriptional control
Atherosclerosis
Post-angioplasty restenosis
Inflammation
Angiogenesis
Cancer |
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| Society Memberships & Professional Activities: | |
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Australian Society for Medical Research (ASMR, Immediate-Past President) and Australian Vascular Biology Society (AVBS, Past President).
Conference Chair, International Vascular Biology Meeting 2008, Sydney, June 1-5 (visit www.ivbm2008.com)
Prizes and Distinctions:
2007 OSMR Eureka James Callachor Prize for Medical Research
2006 GlaxoSmithKline Award for Research Excellence
2006 Wakefield Medal for Research Supervision
2005 First Prize, Khwarizmi International Award for Science and Technology
2005 NHMRC Senior Principal Research Fellowship
2004 Australasian Science Prize
2003 C'wealth Health Minister's Award for Excellence in H/Medical Research
2003 Gottschalk Medal, Australian Academy of Science
2003 Eureka Prize for Scientific Research
2003 Alumni Award for Achievement
2002 NHMRC Principal Research Fellowship
2002 RT Hall Prize, Cardiac Society of Australia & New Zealand
2001 Eppendorf Award for the Young Australian Researcher (Inaugural)
2001 AMGEN Medical Researcher Award
2001 Young Tall Poppy Award
1999 NHMRC Research Fellowship
1997 Glaxo-Wellcome Australia Research Award (NSW)
1997 NHMRC R. Douglas Wright Research Fellowship
1993 NHMRC C.J. Martin Fellowship
1993 J. William Fulbright Award
1993 Rotary Foundation International Ambassadorial Award
1988 Queen Elizabeth II Silver Jubilee Trust Award for Young Australians |
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| Funding Sources: | |
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National Health and Medical Research Council (NHMRC)
Australian Research Council (ARC)
National Heart Foundation of Australia (NHF)
Cancer Institute NSW
Diabetes Australia
Cancer Council NSW |
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| Thesis topics for current UNSW Medicine postgraduate research students: |
| Insights into the function of YRDC, a novel regulator of mRNA translationSignal pathway and transcriptional control in vascular biologyTargeted approaches to c-Jun in models of vascular diseaseTranscriptional regulation of PDGF-DTranscriptional regulation of platelet-derived growth factor - A chain gene expressionVascular smooth muscle cell injury |
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| Key works/Publications: | |
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(Selected publications from >140; in chronologic order 1996-2008)
Khachigian LM, Lindner V, Williams AJ, Collins T. Egr-1-induced endothelial gene expression: a common theme in vascular injury. Science 1996; 271:1427-1431.
Rafty LA, Khachigian LM. Zinc finger transcription factors mediate high constitutive PDGF-B expression in smooth muscle cells derived from aortae of newborn rats. Journal of Biological Chemistry 1998; 273:5758-5764.
Day FL, Rafty LA, Chesterman CN, Khachigian LM. ATII-inducible PDGF A-chain gene expression is p44/42 ERK- and Egr-1/NGFI-A-dependent and mediated via the ATII type 1, but not type 2 receptor: induction by ATII antagonized by nitric oxide. Journal of Biological Chemistry 1999;274:23726-23733.
Santiago FS, Lowe HC, Kavurma MM, Chesterman CN, Atkins DG, Khachigian LM. Novel DNA enzyme targeting NGFI-A mRNA inhibits vascular smooth muscle proliferation and regrowth after injury. Nature Medicine 1999;11:1264-1269.
Rafty LA, Khachigian LM. Identification of a novel negative regulatory element in the proximal region of the platelet-derived growth factor B-chain promoter. Journal of Biological Chemistry 2000;275,11478-11483.
Taylor LM, Khachigian LM. Induction of platelet-derived growth factor B-chain expression by transforming growth factor-beta involves transactivation by Smads. Journal of Biological Chemistry 2000; 275,16709-16716.
Kavurma MM, Santiago FS, Bonfoco E, Khachigian LM. Sp1 phosphorylation regulates apoptosis via extracellular FasL-Fas engagement. Journal of Biological Chemistry 2001; 276:4964-4971.
Rafty LA, Khachigian LM. Sp1 phosphorylation mediates inducible platelet-derived growth factor B-chain gene expression. Nucleic Acids Research 2001: 29: 1027-1033.
Rafty LA, Santiago FS, Khachigian LM. NF1/X represses PDGF A-chain transcription by interacting with Sp1 and antagonizing Sp1 occupancy of the promoter. EMBO Journal 2002; 21, 334-343.
Khachigian LM. DNAzymes: cutting a path to a new class of therapeutics. Current Opinion in Molecular Therapeutics 2002;4:119-121.
Khachigian LM, Fahmy RG, Zhang G, Bobryshev YV, Kaniaros A. c-Jun regulates vascular smooth muscle cell growth and neointima formation after arterial injury: inhibition by a novel DNAzyme targeting c-Jun. Journal of Biological Chemistry 2002;277:22985-22991.
Kavurma MM, Bobryshev YV, Khachigian LM. Ets-1 positively regulates Fas Ligand transcription via co-operative interactions with Sp1. Journal of Biological Chemistry 2002;277:36244-36252.
Francis DJ, Parish CR, McGarry M, Santiago FS, Lowe HC, Brown KJ, Bingley J, Hayward IP, Cowden WB, Campbell JH, Campbell GR, Chesterman CN, Khachigian LM. Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling and inhibits proliferation. Circulation Research 2003;92:E70-77.
Zhang C, Kavurma MM, Lai A, Khachigian LM. Ets-1 protects vascular smooth muscle cells from undergoing apoptosis by activating p21WAF1/Cip1: Ets-1 regulates basal and inducible p21WAF1/Cip1 transcription via distinct cis-acting elements in the p21WAF1/Cip1 promoter. Journal of Biological Chemistry 2003;278:27903-27909.
Kavurma MM, Khachigian LM. Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells by repressing p21WAF1/Cip1 transcription and cyclin D1/Cdk4/p21WAF1/Cip1 complex formation. Journal of Biological Chemistry 2003;278:32537-32543.
Fahmy RG, Dass CR, Sun LQ, Chesterman CN, Khachigian LM. Zinc finger transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth. Nature Medicine 2003;9:1026-1032.
Zhang G, Dass CR, Sumithran E, Di Girolamo NR, Sun L-Q, Khachigian LM. Effect of deoxyribozymes targeting c-Jun on solid tumor growth and angiogenesis in rodents. Journal of the National Cancer Institute 2004;96:683-696.
Fahmy RG, Khachigian LM. Locked nucleic acid modified DNA enzymes targeting early growth response-1 inhibit human vascular smooth muscle cell growth. Nucleic Acids Research 2004;32:2281-2285.
Mitchell A, Dass CR, Sun LQ, Khachigian LM. Inhibition of human breast carcinoma proliferation, migration, chemoinvasion and solid tumor growth by DNAzymes targeting the zinc finger transcription factor EGR-1. Nucleic Acids Research 2004;32:3065-9.
Santiago FS, Khachigian LM. Ets-1 stimulates platelet-derived growth factor A-chain gene transcription and vascular smooth muscle cell growth via co-operative interactions with Sp1. Circulation Research 2004;95:479-487.
Bonello M, Khachigian LM. Fibroblast growth factor-2 represses platelet-derived growth factor receptor-alpha transcription via ERK1/2-dependent Sp1 phosphorylation and an atypical cis-acting element in the proximal PDGFR-alpha promoter. Journal of Biological Chemistry 2004; 279:2377-82.
Midgley V, Khachigian LM. Fibroblast growth factor-2 induction of platelet-derived growth factor C-chain transcription in vascular smooth muscle cells is ERK- but not JNK-dependent and mediated by Egr-1. Journal of Biological Chemistry 2004;279:40289-95.
Khachigian LM (ed.). High Risk Atherosclerotic Plaques: Mechanisms, Imaging, Models and Therapy, CRC Press (Boca Raton, FL) (ISBN: 0849330289; Cat No. 3028), 2004.
Khachigian LM (ed.). Synthetic Nucleic Acids as Inhibitors of Gene Expression: Mechanisms, Applications and Therapeutic Implications, CRC Press (Boca Raton, FL) (ISBN: 0849330254; Cat No. 3025), 2004.
Bonello MR, Bobryshev Y, Khachigian LM. Peroxide-inducible Ets-1 mediates platelet-derived growth factor receptor-alpha gene transcription in vascular smooth muscle cells. American Journal of Pathology 2005;167 1149-1159.
Khachigian LM. Suppressing a sick heart. Nature Medicine 2005;11:828-829.
de Mestre AM, Rao S, Hornby JR, Soe-Htwe T, Khachigian LM, Hulett M. EGR1 regulates heparanase gene transcription in tumor cells. Journal of Biological Chemistry 2005: 280:35136-47.
Liu MY, Eyries M, Zhang C, Santiago FS, Khachigian LM. Inducible platelet-derived growth factor D-chain expression by angiotensin II and hydrogen peroxide involves transcriptional regulation by Ets-1 and Sp1. Blood 2006: 107:2322-9.
Khachigian LM. Egr-1 in cardiovascular pathobiology. Circulation Research 2006: 98:186-91.
Zhang G, Luo X, Sumithran E, Pua VSC, Barnetson RS, Halliday GM, Khachigian LM. Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase (MMP)-2 and MMP-9 expression. Oncogene 2006; 25:7260-6.
Bhindi R, Khachigian LM, Lowe HC. DNAzymes targeting the transcription factor Egr-1 reduce myocardial infarct size in the rat ischemia-reperfusion model. Journal of Thrombosis and Haemostasis 2006; 4:1479-83.
Fahmy R, Waldman A, Zhang G, Mitchell A, Tedla N, Cai H, Chesterman CN, Geczy CR, Perry MA, Khachigian LM. Vascular permeability and inflammation are critically-dependent upon the bZIP transcription factor c-Jun. Nature Biotechnology 2006; 24:856-63.
Zhang G, Fahmy RG, N DiGirolamo, Khachigian LM. Basic region-leucine zipper transcription factor c-Jun mediates matrix metalloproteinase-2 expression, microvascular endothelial growth and retinal neovascularization. J Cell Science 2006; 119:3219-26.
Khachigian LM. Health and medical research funding an investment in Australia's future. Medical Journal of Australia 2006; 185:348-9.
Khachigian LM. Collagen antibody-induced arthritis. Nature Protocols 2006; 1: 2512-2516.
Bhindi R, Fahmy RG, Lowe HC, Chesterman CN, Dass CR, Cairns MJ, Saravolac EG, Sun L-Q, Khachigian LM. Brothers in arms: DNAzymes, siRNA and the emerging wave of small molecule nucleic acid-based gene silencing strategies. American Journal of Pathology 2007: 171:1079-88.
Santiago FS, Ishii H, Shafi S, Khurana R, Kanellakis P, Bhindi R, Ramirez M, Bobik A, Martin J, Chesterman CN, Zachary IC, Khachigian LM. Yin yang-1 inhibits intimal thickening by repressing p21WAF1/Cip1 transcription and p21WAF1/Cip1-Cdk4-Cyclin D1 assembly. Circulation Research 2007; 101:146-55.
Khachigian LM. Science never sleeps: Tucker Collins MD, PhD. Endothelium 2007; 14:174-174.
Sanchez-Guerrero S, Midgley VC, Khachigian LM. Angiotensin II induction of PDGF-C expression is mediated by AT1 receptor-dependent Egr-1 transactivation. Nucleic Acids Research 2008: in press.
Kavurma MM, Schoppet M, Bobryshev YV, Khachigian LM, Bennett MR. TRAIL stimulates proliferation of VSMC via activation and induction of insulin-growth factor-1 receptor. Journal of Biological Chemistry 2008; in press
Tan N, Midgley VC, Kavurma MM, Santiago FS, Luo X, Peden R, Fahmy RG, Berndt MC, Molloy MP, Khachigian LM. Angiotensin II-inducible platelet-derived growth factor-D transcription requires specific Ser/Thr residues in the second zinc finger region of Sp1. Circulation Research 2008; in press
Malabanan K, Kanellakis P, Bobik A, Khachigian LM. ATF-4 induced by FGF-2 regulates VEGF-A transcription in vascular SMCs and mediates intimal thickening in rat arteries following balloon injury. Circulation Research 2008; in press |
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