Professor Levon Khachigian

Fields of research: Cardiovascular Medicine and Haematology, Cancer Cell Biology

Contact Details

Phone: +61 2 9385 2537
Email: l.khachigian@unsw.edu.au

Bio

Professor Levon Khachigian is the Director of the Centre for Vascular Research at UNSW, and Head of the Transcription and Gene Targeting Group

Qualifications: BSc(Hons I), PhD, DSc UNSW

Research Interests    
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-” (e.g. DNAzyme, siRNA, microRNA) 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, MSc and Hons projects are available in both these research streams in the Khachigian Lab in 2013 or 2014. If you’re interested, please email l.khachigian@unsw.edu.au asap, sending your CV.


Broad Research Areas    

  • Cardiology and Vascular Disease
  • Cell Biology and Gene Regulation
  • Pathology
  • Cancer
  • Inflammation

Specific Research Keywords    

  • Atherogenesis and Inflammation
  • Cardiology and Vascular Disease
  • Genetics
  • Signalling and Transcription
  • Molecular Mechanisms

Teaching Interests    

  • Molecular pathobiology
  • Molecular biology/transcriptional control
  • Atherosclerosis
  • Post-angioplasty restenosis
  • Inflammation
  • Angiogenesis
  • Cancer
  • Drug discovery

Funding Sources    

  • National Health and Medical Research Council (NHMRC)
  • Australian Research Council (ARC)
  • Cancer Institute NSW (CINSW)
  • National Heart Foundation (NHF)    

Thesis topics for current UNSW Medicine postgraduate research students

  • DNAzymes and neovascular eye conditions.
  • Identifying the transcriptional regulation of DcR1 in vascular smooth muscle cells
  • Mechanisms of vascular disease: targeted control of cancer growth.
  • Regulation of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) expression in vascular smooth muscle cells.
  • Signaling and transcriptional control in cancer cells.

Project Topics for current Honours Students

  • Discovering novel inhibitors of key immediate-early genes by high throughput screening strategies

Prizes and Distinctions
2012 Distinguished Researcher Award, Australian Vascular Biology Society
2010 The Royal Society of Victoria Research Medal
2010 Premier’s Award for Excellence in Translational Cancer Research
2009 Australia Fellowship NHMRC
2009 Rotary International Vocational Excellence Award
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

Society Presidencies

  • Australian Society for Medical Research (ASMR, Past President)
  • Australian Vascular Biology Society (AVBS, Past President)

Conference Organization

  • Executive Organising Committee, 27th Congress of International Society on Thrombosis and Haemostasis, Melbourne 2019
  • Chair, 15th International Vascular Biology Meeting, Sydney 2008
  • Vascular Biology Section Chair & Conference Treasurer, 20th Congress of International Society on Thrombosis and Haemostasis, Sydney 2005

Publications

(Selected publications from >185)

Cai H, Santiago FS, Prado-Lourenco L, Wang B, Patrikakis M, Davenport MP, Maghzal GJ, Stocker R, Parish CR, Chong BH, Lieschke GJ, Wong TW, Chesterman CN, Francis DJ, Moloney FJ, Barnetson RStC, Halliday GM, Khachigian LM. DNAzyme targeting c-jun suppresses skin cancer growth. Science Translational Medicine 2012;4:139ra82

Sanchez-Guerrero E, Chen E, Kockx M, An SW, Chong BH, Khachigian LM. IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM. PLoS ONE 2012;7:e39811

Chan CWS, Kaplan W, Parish CR, Khachigian LM. Reduced retinal microvascular density, improved forepaw reach, comparative microarray and gene set enrichment analysis with c-jun targeting DNA enzyme. PLoS ONE 2012;7:e39160

Malabanan K, Nath A, Khachigian LM. Platelet-derived growth factor-BB mediates cell migration through Induction of activation transcription factor-4 and tenascin C. American Journal of Pathology 2012;180:2590-7

Zhang N, Chan CS, Sanchez-Guerrero E, Khachigian LM. Repression of PDGF-R-alpha after cellular injury involves TNF-alpha, formation of a c-Fos-YY1 complex and negative regulation by HDAC. American Journal of Physiology-Cell Physiology 2012;302:C1590-8

Ishii H, Hulett MD, Li JM, Santiago FS, Parish CR, Khachigian LM. Yin yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. International Journal of Oncology 2012;40:1575-80

Little PJ, Getachew R, Sanchez-Guerrero E, Khachigian LM, Zheng W, Ballinger ML, Osman N.  Genistein inhibits PDGF-stimulated proteoglycan synthesis in vascular smooth muscle without blocking PDGF-beta receptor phosphorylation. Archives of Biochemistry and Biophysics 2012;525:25-31

Bhindi R, Fahmy RG, McMahon AC, Khachigian LM, Lowe HC. Intracoronary delivery of DNAzymes targeting human EGR-1 reduces infarct size following myocardial ischaemia reperfusion. Journal of Pathology 2012;227:157-64

Perdomo J, Jiang X-M, Khachigian LM, Chong BH. SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4. PLoS ONE 2012; in press

Sanchez-Guerrero E, Jo SR, Chong BH, Khachigian LM. EGFR and the complexity of receptor crosstalk in the cardiovascular system. Current Molecular Medicine 2012: in press

Hitchins M, Rapkins R, Chau-To K, Srivastava S, Wong J, Khachigian LM, Polly P, Goldblatt J, Ward RL. Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5'UTR. Cancer Cell 2011;20:200-13

Chen JB, Liu M, Parish CR, Chong BH, Khachigian LM. Nuclear import of early growth response-1 involves importin-7 and the novel nuclear localization signal serine-proline-serine.  International Journal of Biochemistry & Cell Biology 2011;43:905-12.

Li D, Bhindi R, Khachigian LM. Recent developments in drug eluting stents. Journal of Molecular Medicine 2011;89:545-53

Truong A, Wong TY, Khachigian LM. Emerging therapeutic approaches in the management of retinal angiogenesis and edema. Journal of Molecular Medicine 2011; 89:343-61

Beck K, Wu BJ, Ni J, Santiago FS, Malabanan K, Li C, Wang Y, Khachigian LM, Stocker R. Interplay between heme oxygenase-1 and the multifunctional transcription factor Yin Yang 1.  Circulation Research 2010;107:1490-7

Liang SX, Pinkevych M, Khachigian LM, Parish CR, Davenport MP, Chong BH. Drug-induced thrombocytopenia: Development of a novel NOD/SCID mouse model to evaluate clearance of circulating platelets by drug-dependent antibodies and the efficacy of IVIG. Blood 2010;116:1958-60

Chan JC, Prado-Lourenco L, Khachigian LM, Di Bartolo B, Bennett MR, Kavurma MM.  TRAIL promotes VSMC proliferation and neointima formation after arterial injury in a FGF-2, Sp1 and NFkappaB-dependent manner. Circulation Research 2010;106:1061-71

Wang B, Chen J, Santiago FS, Janes M, Kavurma MM, Chong BH, Pimanda JE, Khachigian LM. Phosphorylation and acetylation of histone H3 and autoregulation by EGR-1 mediate IL-1beta induction of EGR-1 transcription.  Arteriosclerosis, Thrombosis and Vascular Biology 2010;30:536-45

Ni J, Waldman A, Khachigian LM. c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits and intimal hyperplasia in human saphenous veins. Journal of Biological Chemistry 2010;285:4038-48

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

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

University role

Professor & Director

SEO tags

  • Cardiovascular System and Diseases
  • Cancer and Related Disorders

Location

Lowy Cancer Research Centre

Publications