| Research at Medicine |
| Professor Levon Khachigian |
 | Phone: 02 9385 2537 |  |
| Email: |
| Qualifications: BSc(Hons I), PhD, DSc UNSW |
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| School/Unit: |
| Centre for Vascular Research
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| Broad Research Areas: | |
| Cardiology and Vascular Disease
Cell Biology and Gene Regulation
Pathology
Cancer
Inflammation | |
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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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Cardiovascular disease and cancer remain the most prevalent causes of morbidity and mortality. The pathogenesis of these and a myriad of related diseases is underpinned by molecular and cellular changes in our blood vessels. Professor Levon Khachigian’s research is uncovering key networks of transcriptional control and inducible gene-regulatory circuits that lead to vascular disease. The group is also developing new experimental drugs that have the potential to treat a diverse range of health problems, from cancer and inflammation through to eye and heart disease. Professor Khachigian’s research program has two major objectives: 1. To better understand how harmful genes are controlled in vascular cells. This arm investigates signaling and transcriptional mechanisms of pro-inflammatory cytokine-dependent gene expression, post-translational mechanisms that modify protein behavior, proteinase control, the isolation and characterization of new genes induced or repressed by vascular cell injury, and the molecular control of vascular cell migration and proliferation. The group has considerable expertise in animal models of neointima formation, angiogenesis, tumor growth, myocardial ischemia, and inflammation. 2. To develop new vascular therapeutic agents. The lab is harnessing the outcomes of its fundamental research by pioneering the development of novel “anti-gene-” and “gene-therapeutic” strategies targeting key regulatory genes in a myriad of vascular disorders. This involves strategic collaborations with a range of clinical specialists, academics and drug development consultants. -------> PhD and Hons projects are available in both these research streams in Khachigian Lab in 2010. If you’re interested, please email l.khachigian@unsw.edu.au asap, sending your CV. |
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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, Past President) and Australian Vascular Biology Society (AVBS, Past President). Conference Chair, 15th International Vascular Biology Meeting 2008, Sydney (June 1-5)
Prizes and Distinctions:
2009 Australia Fellowship NHMRC
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 |
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| Key works/Publications: | |
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(Selected publications from >150; 1996-present)
Liu MY, Khachigian LM. HDAC-1 is enriched at the PDGF-D promoter in response to IL-1beta and forms a cytokine-inducible gene silencing complex with NF-kappaB p65 and IRF-1. Journal of Biological Chemistry 2009: in press
Tan N, Li JM, Stocker R, Khachigian LM. Angiotensin II-inducible smooth muscle cell apoptosis involves the AT2 receptor, GATA-6 activation and FasL-Fas engagement. Circulation Research 2009:105:422-30
Luo X, Cai H, Ni J, Bhindi R, Lowe HC, Chesterman CN, Khachigian LM. c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury. Arteriosclerosis, Thrombosis and Vascular Biology 2009: 29:1836-42
Zhang N, Khachigian LM. Injury-induced platelet-derived growth factor receptor-alpha expression mediated by interleukin-1beta (IL-1beta) release and cooperative transactivation by NF-kappaB and ATF-4: IL-1beta facilitates HDAC-1/2 dissociation from promoter. Journal of Biological Chemistry 2009; 284:27933-43
Tan NY, Khachigian LM. Sp1 phosphorylation and its regulation of gene transcription. Molecular and Cellular Biology 2009; 29:2483-8
Abdel-Malak NA, Mayaki D, Khachigian LM, Hussain SNA. Early growth response-1 regulates angiopoeitin-1-induced endothelial cell proliferation, migration and differentiation. Arteriosclerosis, Thrombosis and Vascular Biology 2009; 29:209-16
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; 103:378-87
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; 102:e38-51
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
Fahmy RG, Waldman A, Zhang G, Mitchell A, Tedla N, Cai H, Chesterman CN, Geczy CR, Perry MA, Khachigian LM. Suppression of vascular permeability and inflammation by targeting of the transcription factor c-Jun. Nature Biotechnology 2006; 24: 856-863
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
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
Zhang G, Dass CR, Sumithran E, Di Girolamo NR, Sun LQ, 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, 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
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
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
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
Lowe HC, Fahmy RG, Kavurma MM, Baker A, Chesterman CN, Khachigian LM. Catalytic oligodeoxynucleotides define a critical regulatory role for early growth response factor-1 in the porcine coronary artery model of in-stent restenosis. Circulation Research 2001;89:670-677
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;5:1264-1269
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 |
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