Cardiovascular and Tumourivascular Laboratory
The group focuses on the discovery of new membrane and other targets in cardiovascular diseases and cancer. Each of the four projects begins with the development of novel antibodies which provide us with the tools for basic research and a pipeline for translational research. The translational model involves a collaboration with a biotech start-up company.
Antibodies have been raised against G protein-coupled receptors (GPCR) including extracellular epitopes, which have been notoriously elusive. Antibodies against one such epitope within this domain of the calcitonin receptor (CTR) have been useful for live staining of cells undergoing stress and programmed cell death, as well as expression in inflammation and brain tumours. An anti-NPY1 receptor antibody has also been characterised for studies on breast cancer and appetite. Both antibodies bind unique epitopes in the extracellular domains of their respective GPCR.
As an example of project development, the brain tumour (glioblastoma, GBM) project began with collaboration between our laboratory and neurosurgeons at the Alfred and led to the discovery of expression of CTR by glioma stem cells (GSCs, cancer stem cells). The pathway to the clinic has involved the development of an immunotoxin with an anti-CTR antibody conjugated to a plant toxin and the induction of cell death of GSCs.
- Professor David Hare
- Dr Peter Wookey
- Pragya Gupta - PhD Student
Dr Sebastian Furness (ARC Future Fellow), Drug Discovery Laboratories, Monash University, Royal Parade, Parkville. Studies with unique antibodies directed against an extracellular epitope of members of the family B GPCRs including CTR and NPY1R.
Assist/Prof Paula Soares, Department of Pathology and Oncology, Medical Faculty of Porto, Porto, Portugal. Calcitonin receptor expression in medullary thyroid carcinomas.
Prof Hendrik Fuchs, Institute for Laboratory Medicine, Charité UniversitätMedizin, Berlin, Germany. Enhancer therapy to improve efficacy of a novel immunotoxin in the treatment of glioblastoma multiforme.
Assoc/Prof Hui Gan and Professor Andrew Scott, Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute. The testing of anti-CTR immunotoxin to restrict sc. tumour expansion in mouse subcutaneous xenograft models.
International PhD scholarship(s) from the University of Melbourne, philanthropic funds, funds from the pharmaceutical industry and small institutional grants. Other grant applications (ARC and NHMRC) are pending.
Gilabert-Oriol R, Weng A, Trautner A, Weise C, Schmid D, Bhargava C, Niesler N, Wookey PJ, Fuchs H, Thakur M. Combinatorial approach to increase efficacy of Cetuximab, Panitumumab and Trastuzumab by dianthin conjugation and co-application of SO1861. Biochem Pharmacol 2015;97(3): 247-255.
Bullock CM, Wookey PJ, Bennett A, Mobasheri A, Dickerson I, Kelly S. Increased peripheral calcitonin gene-related peptide receptor signalling drives mechanical sensitization of the joint in rat models of osteoarthritic pain. Arthritis & Rheumatology 2014;66(8): 2188-2200.
Sharma V, Ling TW, Rewell S, Howells DW, Hare DL, Kourakis A, Wookey PJ. A novel population of α–smooth muscle actin –positive cells activated in a rat model of stroke: an analysis of the spatio-temporal distribution in response to ischaemia. J Cerebral Blood Flow Metab 2012;32(11): 2055-2065.
Wookey PJ, Turner K, Furness J. Transient expression of the calcitonin receptor by enteric neurons in the embryonic and immediately post-natal period in the mouse. Cell Tissue Res 2012;347: 311-317.
Potes CS, Boyle CN, Wookey PJ, Riediger T, Lutz TA. Involvement of the extracellular-signal regulated kinase 1/2 signalling pathway in amylin’s eating inhibitory effect. Am J Physiol (Reg. Integr. Comp. Physiol.) 2012;302: R340-R351.
Wookey PJ, McLean CA, Hwang P, Furness SGB, Nguyen S, Kourakis A, Hare DL, Rosenfeld JV. The expression of calcitonin receptor detected in malignant cells of the brain tumour glioblastoma multiforme and functional properties in the GBM cell line A172. Histopathol 2012;60: 895-910.
Wookey PJ, Zulli A, Lo C, Hare DL, Schwarer AP, Darby IA, Leung A. Calcitonin receptor (CTR) expression in embryonic, foetal and adult tissues: developmental and pathophysiological implications. In: “The calcitonin gene-related peptide family; form, function and future perspectives”, Eds Debbie L Hay & Ian M Dickerson. Netherlands: Springer. 2010, pp199-233 [ISBN: 978-90-481-2908-9].
Wookey PJ. A review of calcitonin receptor expression in embryonic, foetal and adult tissues with a hypothesis on the connection between expression during foetal development and disease. TheOpenZoology Journal 2009;2: 77-85.
Wookey PJ, Zulli A, Hare DL. The elevated expression of calcitonin receptor by cells recruited into the endothelial layer and neo-intima of atherosclerotic plaque. Histochem Cell Biol 2009;132 (2): 181-9.
Wookey PJ, Zulli A, Buxton BF, Hare DL. Calcitonin receptor immunoreactivity associated with specific cell types in diseased radial and internal mammary arteries. Histopathol 2008;52: 605-612.
School Research Themes
For further information about this research, please contact Group Leader Dr Peter J Wookey
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