Levon Khachigian

Khachigian was born to Armenian parents who served as evangelical missionaries in the Middle East{{cite web|url=http://www.smh.com.au/articles/2003/08/14/1060588496911.html |title=Gene result a touch of shear brilliance|website=Sydney Morning Herald|date=14 August 2003}} and migrated to Australia at age 18 months. He was raised in Naremburn, New South Wales, Australia, and attended Naremburn Public School and later Crows Nest Boys' High School.{{cite web|url=http://www.aips.net.au/wp-content/uploads/2011/03/Artery-Health.pdf |title= Tall Poppies in Flight|website=Australian Institute of Policy and Science|last1=Khachigian|first1=Levon}}

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.

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{{cite journal|last1=Khachigian|first1=LM|journal=Science|date=1996|volume=271|issue=5254|pages=1427–31|title=Egr-1-induced endothelial gene expression: a common theme in vascular injury|display-authors=etal|doi=10.1126/science.271.5254.1427|pmid=8596917|bibcode=1996Sci...271.1427K|s2cid=36935337}}{{cite journal|last1=Khachigian|first1=LM|journal=Circ Res|date=2006|volume=98|issue=2|pages=186–91|title=Early growth response-1 in cardiovascular pathobiology|doi=10.1161/01.res.0000200177.53882.c3|pmid=16456111|doi-access=free}}{{cite journal|last1=Tan|first1=NY|journal=Mol Cell Biol|date=2009|volume=29|issue=10|pages=2483–2488|title=Sp1 phosphorylation and its regulation of gene transcription|display-authors=etal|doi=10.1128/mcb.01828-08|pmid=19273606|pmc=2682032}}{{cite journal|last1=Zhang|first1=N|journal=Am J Physiol Cell Physiol|date=2012|volume=302|issue=11|pages=C1590-8|title=Repression of PDGF-R-alpha after cellular injury involves TNF-alpha, formation of a c-Fos-YY1 complex, and negative regulation by HDAC|display-authors=etal|doi=10.1152/ajpcell.00429.2011|pmid=22322974}}{{cite journal|last1=Khachigian|first1=LM|journal=J Mol Med |date=2016|volume=94|issue=7|pages=747–753|title=Early growth response-1 in the pathogenesis of cardiovascular disease|doi=10.1007/s00109-016-1428-x|pmid=27251707|s2cid=15905744}} and systems-based approaches.{{cite journal|last1=Forrest|first1=AR|journal=Nature|date=2014|volume=507|issue=7493|pages=462–470|title=A promoter-level mammalian expression atlas|display-authors=etal|doi=10.1038/nature13182|pmid=24670764|pmc=4529748|bibcode=2014Natur.507..462T}}{{cite journal|last1=Arner|first1=E|journal=Science|date=2015|volume=347|issue=6225|pages=1010–1014|title=Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells|display-authors=etal|doi=10.1126/science.1259418|pmid=25678556|pmc=4681433|bibcode=2015Sci...347.1010A}} Khachigian has developed a range of interventional approaches to target key regulatory genes for the development of novel therapeutics, particularly catalytic DNA.{{cite journal|last1=Khachigian|first1=LM|journal=J Clin Invest|date=2000|volume=106|issue=10|pages=1189–95|title=Catalytic DNAs as potential therapeutic agents and sequence-specific molecular tools to dissect biological function|doi=10.1172/jci11620|pmid=11086018|pmc=381443}}

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.{{cite journal|last1=Santiago|first1=FS|journal=Nature Medicine|date=1999|volume=5|issue=11|pages=1264–1269|title=New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury|display-authors=etal|doi=10.1038/15215|pmid=10545992|s2cid=9566888}} In 2013 he reported the first clinical use of catalytic DNA in human subjects.{{cite journal|last1=Cho|first1=EA|journal=The Lancet|date=2013|volume=381|issue=9880|pages=1835–1843|title=Safety and tolerability of an intratumorally injected DNAzyme, Dz13, in patients with nodular basal-cell carcinoma: a phase 1 first-in-human trial (DISCOVER)|display-authors=etal|doi=10.1016/s0140-6736(12)62166-7|pmid=23660123|pmc=3951714}} 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{{cite journal|last1=Krug|first1=N|journal= N Engl J Med|date=2015|volume=372|issue=21|pages=1987–95|title=Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme|display-authors=etal|doi=10.1056/nejmoa1411776|pmid=25981191|hdl=1854/LU-6862585|hdl-access=free}} and DNAzymes targeting another nuclear transcription factor GATA3 in patients with allergic asthma{{cite journal|last1=Cao|first1=Y|journal=Mol Ther|date=2014|volume=22|issue=2|pages=371–7|title=Therapeutic evaluation of Epstein-Barr virus-encoded latent membrane protein-1 targeted DNAzyme for treating of nasopharyngeal carcinomas|display-authors=etal|doi=10.1038/mt.2013.257|pmid=24322331|pmc=3916047}} demonstrating DNAzyme efficacy and safety. Targeted catalytic DNA-based molecular therapy may represent a novel, effective and less invasive therapeutic approach in humans.{{cite web|url=http://www.asianscientist.com/health-medicine/drug-dz13-targets-skin-cancer-2013 |title=Dz13 drug targets skin cancer in clinical trial (Asian Scientist 13 May 2013)|date=2013-05-13}}

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{{cite journal|last1=Khachigian|first1=LM|journal=Endothelium|date=2007|volume=14|issue=4–5|pages=173–174|title=Science never sleeps: Tucker Collins MD, PhD|doi=10.1080/10623320701670026}} at Brigham and Women's Hospital, Harvard Medical School, Boston, US. 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. He has been supported by an NHMRC RD Wright Fellowship, Principal Research Fellowship, Senior Principal Research Fellowship and the Australia Fellowship. 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.{{cite web|url=https://newsroom.unsw.edu.au/news/first-class-honours |title=First class honours (UNSW 12 June 2007)|work=UNSW Newsroom |date=2007-06-12 |author1=Anonymous }}

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. He has served as president of the Australian Society for Medical Research and president of the Australian Vascular Biology Society. He is a member of the Faculty of 1000.{{cite web|url=http://f1000.com/prime/thefaculty/member/1835938941930258 |title=F1000 Prime Drug Discovery & Design (14 June 2012)}}

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,{{cite web|url=http://au.gsk.com/en-au/research/gsk-award-for-research-excellence/2006/ |title=Novel and pioneering research offers hope for cardiovascular disease (2006)}} Gottschalk Medal from the Australian Academy of Science, Khwarizmi International Award for Science and Technology, and 3 separate Eureka Prizes from the Australian Museum for scientific research, medical research and international scientific collaboration.

The University of New South Wales investigated matters involving Khachigian in accordance with the Australian Code for the Responsible Conduct of Research. Khachigian maintained there was no wrongdoing{{cite web|url=http://www.abc.net.au/news/2014-04-17/research-investigations-mounting-for-embattled-professor/5397516|title=ABC News (18 April 2014)|website=Australian Broadcasting Corporation |date=2014-04-17}}{{cite web|url=http://www.abc.net.au/reslib/201308/r1157035_14557155.pdf |title=Khachigian statement (11 August 2013)|website=Australian Broadcasting Corporation }} and a trial involving Dz13 was put on hold “to err on the side of caution”.{{cite web|url=http://newsroom.unsw.edu.au/news/general/unsw-response-abc-730-story |title=UNSW statement (12 August 2013)|date=2013-08-12}} Six research articles co-authored by Khachigian have been retracted and one corrected.{{Cite web|url=http://retractiondatabase.org/RetractionSearch.aspx#?auth%3dKhachigian%252c%2bLevon%2bM|title=Retraction Watch Database}} None of the independent external expert panels of inquiry or investigations conducted under the Australian Code made any finding of research misconduct on the part of Khachigian, and they concluded that breaches arose from genuine error or honest oversight.{{cite web|url=https://imgur.com/a/7SEhqZa|title=UNSW public statement (26 November 2015)}}{{cite web|url=http://www.theaustralian.com.au/higher-education/unsw-clears-levon-khachigian-of-all-allegations-of-research-misconduct/news-story/f707b2c14b5cc251a4db5fcbe5778002|title=UNSW clears Levon Khachigian of all allegations of research misconduct (22 December 2015)}} In 2017, a fifth independent external expert panel, set up following the Australian Research Integrity Committee’s review of all previous independent investigations by external experts, came to the same conclusion that there was no finding of research misconduct.{{cite web|url=https://www.abc.net.au/news/2019-10-17/unsw-skin-cancer-levon-khachigian-allegations-and-retractions/11585768|title=UNSW skin cancer researcher Levon Khachigian|website=Australian Broadcasting Corporation |date=16 October 2019}} This decision was discussed in a news article by the Australian Broadcasting Corporation in October 2019. Some members of the panels have expressed concerns about the handling of the investigations.{{Cite news |last=Ryan |first=Jackson |date=September 2023 |title=Science fiction in university labs? |url=https://www.themonthly.com.au/issue/2023/september/jackson-ryan/science-fiction-university-labs |work=The Monthly}}

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• {{Official website|https://research.unsw.edu.au/people/professor-levon-michael-khachigian}}

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Category:Australian biochemists

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Category:Lebanese people of Armenian descent

Category:Australian people of Armenian descent

Category:Scientists from Sydney

Category:University of New South Wales alumni

Category:Academic staff of the University of New South Wales

Category:1964 births

Category:Living people

Category:Scientists from Beirut

Category:Armenian biochemists