Sydney Cancer Center - Gene and Stem Cell Therapy

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Gene and Stem Cell Therapy

Members:
Dr Rose Martiniello-Wilks
Dr Charles Bailey
Dr Jeff Holst
Dr Stephane Flamant

Research Overview
This program located at the Cell and Molecular Therapy Laboratories within RPA and at the Centenary Institute continues to build on its international reputation in (1) the safe introduction of healthy genes (gene therapy) directly into patients with genetic disorders and into stem cells to treat patients with cancers and leukaemias (2) genetic research into the root causes of inherited diseases, cancers and leukaemias with particular expertise applied to cancer genes (transcription factors) and small regulatory genes known as micro RNAs. Our core long term goal is to cure human diseases through a better understanding of cellular and molecular mechanisms. Our core expertise in most gene transfer and adult stem cell technologies has led to extensive national and international collaborations with academic and commercial laboratories.

2007/2008 Highlights
Was awarded over $2M in funding from the Australian Cancer Research Foundation, Cancer Institute of NSW, Cell and Gene Trust and Governments to establish good manufacturing practise Cell and Molecular Therapy Laboratories at RPAH for state-of-the-art cell therapeutic clinical trials in cancer and to promote regenerative medicine.

Publications in the most prestigious medical research journal, Nature Medicine, in 2007 and in 2008, of our results in a clinical trial of gene therapy to treat the serious inherited bleeding disorder, haemophilia. This study performed with colleagues in the USA is a milestone in human gene therapy and suggests significant opportunities to improve this promising experimental technology.

Hosting the largest international meeting of physicians and scientists devoted to the many applications of stem and other cell treatments at the International Society for Cell Therapy in Sydney in June 2007.

Consolidated gene transfer technologies using adenovirus, adeno-associated virus, retrovirus and lentivirus vectors to benefit patients with genetic disorders in future clinical trials.

Refined techniques to study transcription factors and a new set of molecular control molecules (microRNAs) present in normal and cancerous human cells.

Showed that a special type of stem cell that forms the support structure of bone marrow can be coaxed out of its niche – paving the way for their easy collection prior to therapeutic transplantation.

Publications 2007/2008
1. Bailey, CG and Rasko JEJ, Autofluorescent Proteins for Flow Cytometry in Methods in Molecular Biology Book Series, The Humana Press Inc., 2007 411:99-110

2. Kovacic JC, Macdonald P, Freund J, Rasko JEJ, Allan R, Fernandes VB, Ma D, Moore J, Graham RM. Profound thrombocytopenia related to G-CSF, American Journal of Hematology, 2007, 10;82(3):229-230 IF: 1.882

3. Iyengar L, Wang Q, McAvoy JW, Rasko JEJ and Lovicu FJ. The duration of MAPK/ERK1/2 phosphorylation induced by FGF or ocular media determines lens cell fate. Differentiation 2007 83(3):667-78.

4. Lévesque, J-P, Winkler, I.G, Larsen, S.R. and Rasko JEJ, Mobilization of Bone Marrow-derived Progenitors, in Handbook of Experimental Pharmacology, Springer-Verlag, 2007, (180) 3-36.

5. Martiniello-Wilks R and Rasko JEJ, Cell and Gene Therapy in Australia, Cytotherapy, 2007, 9(3):209-221.

6. Hayward MD, Pötgens AJG, Drewlo S, Kaufmann P and Rasko JEJ, Distribution of Human Endogenous Retrovirus type W Receptor in Normal Human Villous Placenta, Pathology, 2007, 39:4, 406 - 412

7. Mingozzi F, Maus M, Hui D, Sabatino D, Murphy S, Rasko JEJ, Ragni M, Manno C, Sommer J, Jiang H, Pierce G, Ertl H and High KA, CD8+ T cell responses to AAV capsid in humans, Nature Medicine, 2007;13(4):419-22

8. Azmanov DN, Rodgers H, Auray-Blais C, Giguère R, Bailey C, Bröer S, Rasko JEJ, Cavanaugh JA, Persistence of the common Hartnup disease D173N allele in populations of European origin, Annals of Human Genetics. 2007;71(Pt 6):755-61.

9. Baoutina, A, Alexander, IE, Rasko, JEJ, Emslie KR, Potential use of gene transfer in athletic performance enhancement, Molecular Therapy, 2007;15(10):1751-66.

10. Horan KA, Watanabe K, Kong AM, Bailey CG, Rasko, JEJ, Sasaki T, Mitchell CA., Regulation of FcγR-stimulated phagocytosis by the 72 kDa inositol polyphosphate 5-phosphatase: SHIP1, but not the 72 kDa 5-phosphatase, regulates complement receptor-3-mediated phagocytosis, by differential recruitment of these 5-phosphatases to the phagocytic cup, Blood, 2007 ;110(13):4480-91

11. Baoutina A, Alexander IE, Rasko JEJ, Emslie KR. Developing strategies for detection of gene doping, The Journal of Gene Medicine 2008;10(1):3-20.

12. Sonja Kowalczuk, Angelika Bröer, Nadine Tietze, Jessica M. Vanslambrouck, Rasko JEJ, Stefan Bröer A protein complex in the brush-border membrane explains a Hartnup disorder allele, FASEB J., 2008;22(8):2880-7

13. Azmanov DN, Kowalczuk S, Rodgers H, Auray-Blais C, Giguère R, Rasko JEJ, Bröer S, Cavanaugh JA. Further evidence for allelic heterogeneity in Hartnup disorder. Human Mutation, Epub May 2008

14. Larsen, SR, Chng, K, Battah, F, Martiniello-Wilks, R and Rasko JEJ Improved G-CSF mobilization of hemopoietic progenitors using cytokine combinations in primates, Stem Cells, 2008; 26: 2974-2980

15. Power C and Rasko JEJ, Whither Prometheus’ Liver? Greek Myth and the Science of Regeneration, Annals of Internal Medicine, 2008;149(6):421-6

16. Bröer, S*, Bailey CB*, Kowalczuk, S, Ng, C, Vanslambrouck, JM, Rodgers, H, Auray-Blais, C, Cavanaugh, JS, Bröer, A and Rasko JEJ, Iminoglycinuria and hyperglycinuria are discrete phenotypes explained by complex mutations in proline and glycine transporters, J. Clinical Investigation, 2008 Nov 6. [Epub ahead of print]