| Research at Medicine |
| Professor Levon Khachigian |
 | Phone: 02 9385 2537 |  |
| Email: |
| Qualifications: BSc, PhD, DSc UNSW |
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| School/Unit: |
| 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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Cardiovascular disease and cancer remain the most important 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. A molecular and vascular biologist, Professor Levon Khachigian and his team have discovered key networks of transcriptional control and inducible gene-regulatory circuits. They have also developed a new class of experimental drug that has the potential to treat a diverse range of health problems, from cancer and inflammation through to eye and heart disease. Clinical trials will commence in skin cancer patients in 2009. Professor Khachigian's research group at the UNSW Centre for Vascular Research 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 in 2009 or 2010, 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:
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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| Thesis topics for current UNSW Medicine postgraduate research students: |
| Insights into the function of YRDC, a novel regulator of mRNA translation.Signal pathway and transcriptional control in vascular biologyTargeted approaches to c-Jun in models of vascular disease.The mechanistic involvement of trail in vascular biology and atherosclerosis.Transcriptional regulation of platelet-derived growth factor - A chain gene expression.Vascular smooth muscle cell injury |
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| Key works/Publications: | |
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(Selected publications from >145; 1996-present)
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: in press
Tan NY, Khachigian LM. Sp1 phosphorylation and its regulation of gene transcription. Molecular and Cellular Biology 2009; in press
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; 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; 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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