The Achen laboratory is focused on characterising key molecular signalling events in the tumour microenvironment that facilitate the growth and spread of cancer.
The ultimate aim is to therapeutically target these signalling events to block tumour progression.
Research in the laboratory is enabled by the expertise and resources of Peter Mac’s Molecular Pathology laboratory, Victorian Centre for Functional Genomics, Bioinformatics facility, Flow Cytometry facility, Microscopy and Histology facility, pre-clinical research models and Tissue Bank.
For information on potential collaborative or contract research agreements, or material transfer agreements with this laboratory, contact Peter Mac’s Technology Transfer Office.
Identify the miRNA network controlling the vascular response to cancer
MicroRNAs (miRNAs) are critical for coordinating the regulation of key biological processes in the tumour vasculature, such as sprouting growth and the remodelling of blood vessels and lymphatics. Vascular remodelling is already a well-validated target for anti-cancer therapeutics, but there is much room for improving drugs that target signalling in the blood vessels and lymphatics of tumours. We are using systems biology approaches focused on miRNAs to identify novel therapeutic targets associated with blood vessels and lymphatics in cancer.
Define molecular mechanisms controlling the remodelling of blood vessels and lymphatics in cancer
The vascular endothelial growth factors (VEGFs) are secreted proteins produced by tumour cells that induce angiogenesis and lymphangiogenesis in cancer, and thereby promote tumour growth and spread. We are characterising the structure/function relationship for members of the VEGF family to better understand how they function in cancer, and to inform potential therapeutic strategies to target these proteins in the clinic.
Sato T, Paquet-Fifield S, Harris NC, Roufail S, Turner DJ, Yuan Y, Zhang YF, Fox SB, Hibbs ML, Wilkinson-Berka JL, Williams RA, Stacker SA, Sly PD, Achen MG (2016). VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury. J Pathol. 239(2):152-61.
Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB and Achen MG (2014). Lymphangiogenesis and lymphatic vessel remodeling in cancer. Nat Rev Cancer.
Harris NC, Davydova N, Roufail S, Paquet-Fifield S, Paavonen K, Karnezis T, Zhang YF, Sato T, Rothacker J, Nice EC, Stacker SA, Achen MG (2013). The propeptides of VEGF-D determine heparin binding, receptor heterodimerization, and effects on tumor biology. J Biol Chem. 288(12):8176-86.
Paquet-Fifield S, Levy SM, Sato T, Shayan R, Karnezis T, Davydova N, Nowell CJ, Roufail S, Ma GZ, Zhang YF, Stacker SA, Achen MG (2013). Vascular endothelial growth factor-d modulates calibre and function of initial lymphatics in the dermis. J Invest Dermatol. 133(8):2074-84.
Karnezis T, Shayan R, Caesar C, Roufail S, Harris NC, Ardipradja K, Zhang YF, Williams SP, Farnsworth RH, Chai MG, Rupasinghe TW, Tull DL, Baldwin ME, Sloan EK, Fox SB, Achen MG, Stacker SA (2012). VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell. 21(2):181-95.
François M, Caprini A, Hosking B, Orsenigo F, Wilhelm D, Browne C, Paavonen K, Karnezis T, Shayan R, Downes M, Davidson T, Tutt D, Cheah KS, Stacker SA, Muscat GE, Achen MG, Dejana E, Koopman P (2008). Sox18 induces development of the lymphatic vasculature in mice. Nature. 456(7222):643-7.
Achen MG, McColl BK, Stacker SA (2005). Focus on lymphangiogenesis in tumor metastasis. Cancer Cell. 7(2):121-7.
McColl BK1, Baldwin ME, Roufail S, Freeman C, Moritz RL, Simpson RJ, Alitalo K, Stacker SA, Achen MG (2003). Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D. J Exp Med. 198(6):863-8.