Levon Khachigian

Levon Michael Khachigian (born 6 March 1964 in Beirut, Lebanon)[1] is an Australian medical research scientist notable for his work in vascular cell and molecular biology.[2] He is a Professor in the Faculty of Medicine at the University of New South Wales.[3]

Khachigian is known for his studies in the area of transcriptional control and for translating basic discoveries into potential novel therapeutics. He is the inventor of the experimental drug Dz13, which may help treat a range of common diseases or complications including skin cancer, post-angioplasty restenosis, macular degeneration and asthma.[1][2][4]

Early life and education

Khachigian was born to Armenian parents who served as evangelical protestant missionaries in the Middle East[5] and migrated to Australia at age 18 months. He was raised in Naremburn, New South Wales, Australia[1] and attended Naremburn Public School and later Crows Nest Boys' High School.[6]

Khachigian obtained a B.Sc. with first-class honours in biochemistry in 1986 and Ph.D. in growth factor biochemistry and cell biology in 1993 from the University of New South Wales. He performed doctoral research at the School of Medicine, St George Hospital (Sydney), Division of Biomolecular Engineering, Commonwealth Scientific and Industrial Research Organisation and Department of Haematology, Prince of Wales Hospital (Sydney). He obtained a D.Sc. in vascular biology and transcriptional control in 2004 from the University of New South Wales.[2][3]

Research

Khachigian is a vascular biologist with a strong focus on "bench to bedside" translational research. His research has centered mainly on interrogating the roles of immediate-early genes (such as Egr1 and c-Jun) as molecular switches in the pathogenesis of disease. He and his collaborators have uncovered regulatory networks underpinning waves of transcriptional change in cellular activation in a range of single gene[7][8][9][10][11] and systems-based approaches.[12][13] Khachigian has developed a range of interventional approaches to target key regulatory genes for the development of novel therapeutics, particularly catalytic DNA.[14]

Khachigian invented Dz13, a molecule that targets the transcription factor c-Jun, implicated in a range of common proliferative, occlusive and inflammatory diseases. In 1999 Khachigian reported the first use of catalytic DNA as new experimental drugs in an animal model of any kind.[15] In 2013 he reported the first clinical use of catalytic DNA in human subjects.[16] This was later followed by numerous other independent, some multi-center, clinical trials evaluating DNAzymes in humans, including DNAzymes targeting EBV-LMP1 in patients with nasopharyngeal cancer[17] and DNAzymes targeting another nuclear transcription factor GATA3 in patients with allergic asthma[18] demonstrating DNAzyme efficacy and safety. Targeted catalytic DNA-based molecular therapy may represent a novel, effective and less invasive therapeutic approach in humans.[19]

Career

After obtaining his Ph.D. and with the support of a CJ Martin Research Fellowship from the National Health and Medical Research Council of Australia and Fulbright Program, Khachigian studied vascular biology and transcriptional control with Professor Tucker Collins[20] at Brigham and Women’s Hospital, Harvard Medical School, Boston USA. On returning to Australia in 1996 he established the Transcription Laboratory within the Centre for Vascular Research, Faculty of Medicine at the University of New South Wales.[6] He has been supported by an NHMRC RD Wright Fellowship, Principal Research Fellowship, Senior Principal Research Fellowship and the Australia Fellowship.[3] In 2004 Khachigian was appointed Professor in Medicine and in 2009 appointed Director of the Centre for Vascular Research, succeeding its Foundation Director Scientia Professor Colin Chesterman AO.[2][21]

Service

Khachigian has a strong record of service to international and national scientific societies and has been at the helm of numerous international conferences in vascular biology, drug design and discovery, and interdisciplinary health and medical research, including the International Vascular Biology Meeting and Congress of the International Society on Thrombosis and Haemostasis.[2] He has served as President of the Australian Society for Medical Research and President of the Australian Vascular Biology Society.[1][3] He is a member of the Faculty of 1000.[22]

Awards

Khachigian has received numerous prestigious national and international awards including the Commonwealth Health Minister's Award for Excellence in Health and Medical Research, GlaxoSmithKline Award for Research Excellence,[23] Gottschalk Medal from the Australian Academy of Science, Khwarizmi International Award for Science and Technology, and two separate Eureka Prizes from the Australian Museum for Scientific Research and for Medical Research.[3]

Investigations

The University of New South Wales advised in 2015 that over a period of several years it investigated matters involving Khachigian in accordance with the Australian Code for the Responsible Conduct of Research.[24] Khachigian maintained there was no wrongdoing.[25] UNSW commissioned multiple different, independent external panels of inquiry or reports pursuant to the Australian Code.[24] During this time a clinical trial involving Dz13 was put on hold “to err on the side of caution”.[26] Khachigian released a statement in reply to questions posed to him in 2013 in which he asserted that he commissioned a range of measures to verify the data in question including data reanalysis, new mouse tumor experiments and external inspection of data that confirmed its veracity.[27] UNSW advised that Khachigian's work was approved by ethics committees and that funding bodies were informed.[24] Independent external panel investigating concerns in relation to Dz13 and other publications appointed in 2011 made no finding of research misconduct.[26] UNSW further advised in 2015 that multiple subsequent independent external inquiry panels of inquiry found genuine error.[24]

References

  1. 1 2 3 4 "To crack the maze (Sydney Morning Herald 27 April 2006)".
  2. 1 2 3 4 5 "Levon M. Khachigian: IJO Editorial Academy (September 2012)".
  3. 1 2 3 4 5 "LM Khachigian website".
  4. ↑ "Wide role for new drug targeting skin cancer gene (Sydney Morning Herald 7 May 2013)".
  5. ↑ "Gene result a touch of shear brilliance (Sydney Morning Herald, 14 August 2003".
  6. 1 2 "Tall Poppies in Flight: Australian Institute of Policy and Science" (PDF).
  7. ↑ Khachigian, LM; et al. (1996). "Egr-1-induced endothelial gene expression: a common theme in vascular injury". Science. 271: 1427–31. doi:10.1126/science.271.5254.1427.
  8. ↑ Khachigian, LM (2006). "Early growth response-1 in cardiovascular pathobiology". Circ Res. 98: 186–91. doi:10.1161/01.res.0000200177.53882.c3.
  9. ↑ Tan, NY; et al. (2009). "Sp1 phosphorylation and its regulation of gene transcription". Mol Cell Biol. 29: 2483–2488. doi:10.1128/mcb.01828-08.
  10. ↑ Zhang, N; et al. (2012). "Repression of PDGF-R-alpha after cellular injury involves TNF-alpha, formation of a c-Fos-YY1 complex, and negative regulation by HDAC". Am J Physiol Cell Physiol. 302: C1590-1598. doi:10.1152/ajpcell.00429.2011.
  11. ↑ Khachigian, LM (2016). "Early growth response-1 in the pathogenesis of cardiovascular disease". J Mol Med. 94: 947–531. doi:10.1126/science.271.5254.1427.
  12. ↑ Forrest, AR; et al. (2014). "A promoter-level mammalian expression atlas". Nature. 507: 462-470.
  13. ↑ Arner, E; et al. (2015). "Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells". Science. 347: 1010-1014.
  14. ↑ Khachigian, LM (2000). "Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function". J Clin Invest. 106: 1189–95. doi:10.1172/jci11620.
  15. ↑ Santiago, FS; et al. (1999). "New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury". Nature Med. 5: 1264–1269. doi:10.1038/15215.
  16. ↑ Cho, EA; et al. (2013). "Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER)". The Lancet. 381: 1835–1843. doi:10.1016/s0140-6736(12)62166-7.
  17. ↑ Krug, N; et al. (2015). "Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme". N Engl J Med. 372: 1987–95.
  18. ↑ Cao, Y; et al. (2014). "Therapeutic evaluation of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme for treating of nasopharyngeal carcinomas". Mol Ther. 22: 371–7.
  19. ↑ "Dz13 drug targets skin cancer in clinical trial (Asian Scientist 13 May 2013)".
  20. ↑ Khachigian, LM (2007). "Science never sleeps: Tucker Collins MD, PhD". Endothelium. 14: 173–174. doi:10.1080/10623320701670026.
  21. ↑ "First class honours (UNSW 12 June 2007)".
  22. ↑ "F1000 Prime Drug Discovery & Design (14 June 2012)".
  23. ↑ "Novel and pioneering research offers hope for cardiovascular disease (2006)".
  24. 1 2 3 4 "UNSW statement (26 November 2015)" (PDF).
  25. ↑ "ABC News (18 April 2014)".
  26. 1 2 "UNSW statement (12 August 2013)".
  27. ↑ "Khachigian statement (11 August 2013)" (PDF).

External links


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