Cancer | Microbiome, Infection, Immunity and Inflammation | Drug Discovery, Development and Delivery | Cardiovascular & Metabolic Disease
The Khachigian Group has 2 principal aims:
To better understand how potentially harmful genes are controlled in vascular cells. This arm investigates signalling and transcriptional mechanisms of growth factor- and/or pro-inflammatory cytokine-dependent gene expression, post-translational mechanisms that modify protein behaviour, characterization of genes that are induced or repressed by acute vascular cell injury, and molecular control in vascular cell migration and proliferation. The group has considerable expertise in preclinical models of cardiovascular disease, inflammation and cancer;
To develop novel vascular therapeutic agents for cardiovascular and inflammatory disease, tumour growth and metastasis. The lab is harnessing the outcomes of its fundamental research by pioneering the development of novel anti-gene, gene-therapeutic and small molecule pharmacological strategies targeting regulatory genes in experimental vascular diseases. These agents may be applied to conditions such as wet age-related macular degeneration. The strategy involves interdigitating in-house laboratory research with national and international collaborations with a range of clinical and preclinical specialists, global contract research organisations, leading industrial medicinal chemists and drug development consultants.
Current projects
- Development of novel anti-inflammatory therapeutics for cardiovascular disease
- Development of novel cancer pharmacotherapeutics
- Development of novel therapeutics for acute respiratory distress syndrome
- Development of novel therapeutics for wet age-related macular degeneration
Likely techniques you will learn: Cell and tissue culture, microscopy, cell proliferation assays, cell migration assays, tubule formation assays, RNA-seq and transcriptomics, Western blotting and quantitation, PCR, histological processing, immunohistochemical staining and analyses, animal handling and experimental models.
Highlighted publications
- Li Y, Wu B, Hossain MJ, Quagliata L, O’Meara C, Wilkins MR, Corley S, Khachigian LM. Flubendazole inhibits PD-1 and suppresses melanoma growth in immunocompetent mice. Journal of Translational Medicine 2023;21:467 http://dx.doi.org/10.1186/s12967-023-04289-y
- Santiago FS, Li Y, Zhong L, Raftery MJ, Lins L, Khachigian LM. Truncated YY1 interacts with BASP1 through a 339KLK341 motif in YY1 and suppresses vascular smooth muscle cell growth and intimal hyperplasia after vascular injury. Cardiovascular Research 2021;cvab021 http://dx.doi.org/10.1093/cvr/cvab021
- Li Y, Alhendi AMN, Yeh MC, Elahy M, Santiago FS, Deshpande NP, Wu B, Chan E, Inam S, Prado-Lourenco L, Marchand J, Joyce RD, Wilkinson-White LE, Raftery MJ, Zhu M, Adamson SJ, Barnat F, Viaud-Quentric K, Sockler J, Mackay JP, Chang A, Mitchell P, Marcuccio SM, Khachigian LM. Thermostable small molecule inhibitor of angiogenesis and vascular permeability that suppresses a pERK-FosB/ΔFosB-VCAM-1 axis. Science Advances 2020;6:eaaz7815 http://dx.doi.org/10.1126/sciadv.aaz7815
- O’Meara C, Coupland L, Kordbacheh F, Quah B, Chang CW, Davis DS, Bezos A … Khachigian LM, et al. Neutralizing the pathological effects of extracellular histones with small polyanions. Nature Communications 2020;11:6408 http://dx.doi.org/10.1038/s41467-020-20231-y
- Forrest AR, Kawaji H, Rehli M, Baillie JK, de Hoon MJ, Haberle V, Lassmann T, Kulakovskiy IV, Lizio M, Itoh M, Andersson R … Khachigian LM, et al. A promoter level mammalian expression atlas. Nature 2014; 507:462-70 http://dx.doi.org/10.1038/nature13182
Our experts
Professor Levon Michael Khachigian - Group Leader
Levon is a molecular and cell biologist with longstanding interests in blood vessel pathology. This means his research spans cardiovascular disease, inflammation, ocular disease and cancer. He has pioneered the development of novel strategies targeting immediate-early genes in multiple experimental vascular proliferative disorders, and successfully directed the bench-to-bedside transition of novel drugs through first-in-human, first-in-class clinical trials.
Levon began his undergraduate studies in science at UNSW in 1982 (majoring in biochemistry and microbiology) and graduated with first class honours in biochemistry in 1986. He became interested in vascular biology at Prince Henry Hospital with the support of a National Heart Foundation Vacation Scholarship then commenced predoctoral studies in Medicine at St George Hospital and Prince of Wales Hospital, gaining valuable training in molecular biology at CSIRO and immunology at the Garvan Institute. After obtaining his PhD in 1993, Levon was awarded a NHMRC CJ Martin Fellowship and trained in vascular pathobiology at Harvard Medical School where he was appointed Instructor. He returned to UNSW in 1996 and established an independent research group in the Centre for Vascular Research (CVR), one of UNSW’s largest research centres. A NHMRC RD Wright Fellowship and a series of NHMRC Research Fellowships followed. Levon was appointed to Professor in 2004 and Director of CVR in 2009. In this role, Levon oversaw the design, construction and CVR’s relocation to Level 3 of the Lowy Cancer Research Building.
Construction of Lowy Cancer Research Centre with former Wallace-Wurth Building façade in background. L-to-R: Profs Murray Norris (CCIA), Nick Hawkins (SOMS), Levon Khachigian (CVR), Geoffrey Leeson (UNSW), Robyn Ward (Fac Med), Lahznimmo Architects, Deth Hatton (CVR), Philip Hogg (ACP).
Levon also holds a DSc from UNSW and a Master of Intellectual Property Law from UTS. He has held appointments as NHMRC Australia Fellow, Senior Principal Research Fellow and Principal Research Fellow. His group’s innovative research has been recognized by several prestigious awards including the Commonwealth Health Minister's Award for Excellence in Health and Medical Research, GSK Award for Research Excellence, Gottschalk Award and 3 Eureka Prizes. He is Past President of the Australian Society for Medical Research, Past President of the Australian Vascular Biology Society and Past Chair, International Vascular Biology Meeting.
Team members
- Dr Yue Li
- Dr Daniel Hu
- Dr Ben Wu
- Dr Connor O’Meara
- Ms Jannie Zhang
- Mr Zuhayr Jafri
- Ms Michaella Noof Albao
Research Theme