Cellular Reprogramming Group

Research Overview

Blindness is one of the most feared disabilities and many common causes of blindness are currently untreatable. The extreme difficulty in obtaining eye tissue from living people currently represents a major barrier to studying and treating blinding diseases. The cellular reprogramming group use induced pluripotent stem cell (iPSC) technology to model eye diseases affecting the optic nerves. We focus on generating patient-specific iPSCs and developing methods to differentiate pluripotent stem cells into retinal ganglion cells (RGCs). Generation of disease-specific iPSCs and RGCs will allow us to study the precise mechanism underlying the pathology of eye diseases, as well as allowing us to screen drugs to improve treatment options and development of gene therapy and cell replacement therapy.

Staff

Dr Shahnaz Khan, visiting scientist;

Mr Maciej Daniszewski, PhD student;

Ms Katie Gills, PhD student

Collaborators

A/Prof Alice Pebay, CERA; Dr Alex Hewitt, CERA; A/Prof Ian Trounce, CERA; Dr Hélène Jousset, WEHI; Prof David Mackey, Lions Eye Institute; Dr Bryony Nayagam, Uni. Melb; A/Prof Robyn Jamieson, Uni. Sydney; Dr Karina Needham, Uni. Melb.; Dr George Wang, Swinburne Uni. Of Tech. ; Dr Max Lim, St Vincent’s Institute; Dr Paul Lockhart, Murdoch Childrens Research Institute; Prof Jamie Craig, Flinders Uni.; Dr Shiwani Sharma, Flinders Uni. ; Dr Tony Cook, Uni. Tas.; A/Prof Nuri Guven, Uni. Tas.; Dr Camden Lo, Monash Uni.; Dr Elaine Sanij, Peter Mac. Cancer Centre

Funding

MAWA fellowship, Medical Advances Without Animals; University of Melbourne Therapeutic technologies research seed funding, ‘Modelling retinoblastoma using human induced pluripotent stem cells’; NHMRC project grant, ‘Modelling Leber’s Hereditary Optic Neuropathy using human induced pluripotent stem cells’; ORIA grant, ‘Automated differentiation of patient derived stem cells into eye cells’

Research Outcomes

1.Hung, S., Van Bergen, N., Jackson, S., Liang, H., Mackey, D., Hernandez, D., Lim, S.Y., Hewitt, A., Trounce, I., Pébay, A., Wong, R. (2016) Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells. Aging, accepted 2016.04.04

2.Phelan, D., Anderson, D., Howden, S., Wong, R., Hickey, P., Pope, K., Wilson, G., Pébay, A., Davis, A., Petrou, S., Elefanty, A., Stanley, E., James, P., Macciocca, I., Bahlo, M., Cheung, M., Amor, D., Elliott, D., Lockhart, P. (2016) ALPK3 deficient cardiomyocytes generated from patient derived iPSCs and mutant hESCs display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy. European Heart Journal, accepted 2016.03.13

3.McCaughey, T., Liang, H., Chen, C., Fenwick, E., Rees, G., Wong, R., Vickers, J., Summers, M., MacGregor, C., Craig, J., Munsie, M., Pebay, A., Hewitt, A. (2016) An interactive multimedia approach to improving informed consent for induced pluripotent stem cell research. Cell Stem Cell, 18(3):307-8

4.Lidgerwood, G., Ali, R., Lim, S.Y., Crombie, D., Gill, K., Hernandez, D., Kie, J., Conquest, A., Waugh, H., Wong, R, Liang, H., Hewitt, A., Davidson, K., Pébay, A. (2015) Defined medium conditions for the induction and expansion of human pluripotent stem cell-derived retinal pigment epithelium. Stem cell Reviews and Reports,  2015 Nov 20.

5.Hernandez, D., Millard, R., Sivakumaran, P., Wong, R., Crombie, D., Hewitt, A., Liang, H., Hung, S., Pébay, A., Shepherd, R., Dusting, G., Lim, S.Y. (2015) Electrical stimulation promotes cardiac differentiation of human induced pluripotent stem cells. Stem Cells International, 2016;2016:1718041.

6.Hung, S., Pébay, A., Wong, R. (2015) Generation of integration-free human induced pluripotent stem cells using hair-derived keratinocytes. Journal of Visualized Experiments, 2015 Aug 20; (102).

7.Gill, K., Hewitt, A., Davidson, K., Pébay, A., Wong, R. (2014) Methods of retinal ganglion cell differentiation from pluripotent stem cells. Translational Vision Science & Technology, 3 (4).

8.Piao, Y., Hung, S., Lim, S., Wong, R.#, Ko, M#. (2014) Efficient generation of integration-free human induced pluripotent stem cells from keratinocytes by simple transfection of episomal vectors. Stem Cell Translational Medicine, 3(7): 787-91. # = equal last author.

9.Pébay, A., Wong, R. (2014) Study of gap junctions in human embryonic stem cells. Methods in Molecular Biology, 2014 May 24 (Epub ahead of print).

10.Peh, G., Wong, R.# (2014) Advances in pluripotent and adult stem cells for eye research. Regenerative Biology of the Eye, Stem Cell Biology and Regenerative Medicine series, Springer publishers, ch5, 101-120. # = Corresponding author.

11.Hung, S., Wong, R., Sharov, A., Nakatake, Y., Yu, H., Ko, M. (2013) Repression of global protein synthesis by Eif1a-like genes that are expressed specifically in the two-cell embryos and the transient Zscan4-positive state of embryonic stem cells. DNA Research, 20(4): 391-402.

12.Fong, H., Wong, R., Donovan, P. (2012) Transcriptional regulation of TRKC by SOX2 in human embryonic stem cells. Stem Cell Research, 8(2), 206-214.

13.Wong, R., Pera, M., Pébay, A. (2012) Maintenance of human embryonic stem cells by sphingosin-1-phostate and platelet-derived growth factor. Methods in Molecular Biology; S-1-P Signalling Methods and Protocols, 874:167-75

14.Wong, R., Pollan, S., Fong, H., Ibrahim, H., Smith, E., Ho, M., Laslett, A., Donovan, P. (2011) A novel role for an RNA polymerase III subunit POLR3G in regulating pluripotency in human embryonic stem cells. Stem Cells, 29(10), 1517-1527.

15.Wong, R., Smith, E., Donovan, P. (2011) New techniques in the generation of induced pluripotent stem cells. Book chapter in Embryonic stem cells: Differentiation and Pluripotent Alternatives, InTech open access publisher, 373-398.

16.Wong, R., Ibrahim, A., Fong, H., Thompson, N., Lock, L., Donovan, P. (2011) L1TD1 is a marker for undifferentiated human embryonic stem cells. PLoS One, Apr 29; 6(4): e19355.

17.Wong, R., Donovan, P., Pébay, A. (2011) Molecular mechanism involved in the maintenance of pluripotent stem cells. Journal of Stem Cells, 2011; 6(4):213-32.

18.Pébay, A., Peshavariya, H., Wong, R., Dusting, G. (2011) Non-Classical Signalling Mechanisms in Stem Cells. Embryonic Stem Cells: The Hormonal Regulation of Pluripotency and Embryogenesis, InTech open access publisher, 317-336.

Professional involvement & international standing:

Speaker at international conferences: ISSCR meeting, USA (2016); TERMIS-AP meeting, Taiwan (2016); IPITA/IXA/CTS joint international congress, Australia (2015); 4th Annual World Congress of Molecular & Cell Biology, China (2014); Optic Nerve Conference, Austria (2013); Asia ARVO conference, India (2013)

Speaker at national conferences (2): Nanobionics (2015); Frontiers in Human Engineering Symposium (2014)

Research seminars at overseas institutes: Karolinska Institutet (2015); NIH (2012); Stanford Uni. (2011); University of California San Francisco (2011); University of California Irvine (2011)

Guest editor for Stem Cell International (2016), Stem Cell Biology and Regenerative Medicine – Lipidomics of Stem Cells (Springer, 2016)

Editorial board member : Recent patents in regenerative medicine (2012-), World Journal of Stem Cells (2011-), Chinese Journal of Biology (2013-), Ophathalmology – open journal (2015-); Ad-hoc reviewer for international journals including Stem Cells, PLoS ONE, , Stem Cells Trans. Med, Stem cell Review and Reports, and Stem Cells and Development; External grant reviewer for NHMRC (2011-) and Ophthalmic Research Institute of Australia  (2013-)

Research Publications

1.Hung, S., Van Bergen, N., Jackson, S., Liang, H., Mackey, D., Hernandez, D., Lim, S.Y., Hewitt, A., Trounce, I., Pébay, A., Wong, R. (2016) Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells. Aging, accepted 2016.04.04

2.Phelan, D., Anderson, D., Howden, S., Wong, R., Hickey, P., Pope, K., Wilson, G., Pébay, A., Davis, A., Petrou, S., Elefanty, A., Stanley, E., James, P., Macciocca, I., Bahlo, M., Cheung, M., Amor, D., Elliott, D., Lockhart, P. (2016) ALPK3 deficient cardiomyocytes generated from patient derived iPSCs and mutant hESCs display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy. European Heart Journal, accepted 2016.03.13

3.McCaughey, T., Liang, H., Chen, C., Fenwick, E., Rees, G., Wong, R., Vickers, J., Summers, M., MacGregor, C., Craig, J., Munsie, M., Pebay, A., Hewitt, A. (2016) An interactive multimedia approach to improving informed consent for induced pluripotent stem cell research. Cell Stem Cell, 18(3):307-8 6.Hung, S., Pébay, A., Wong, R. (2015) Generation of integration-free human induced pluripotent stem cells using hair-derived keratinocytes. Journal of Visualized Experiments, 2015 Aug 20; (102).

4.Gill, K., Hewitt, A., Davidson, K., Pébay, A., Wong, R. (2014) Methods of retinal ganglion cell differentiation from pluripotent stem cells. Translational Vision Science & Technology, 3 (4).

5.Piao, Y., Hung, S., Lim, S., Wong, R.#, Ko, M#. (2014) Efficient generation of integration-free human induced pluripotent stem cells from keratinocytes by simple transfection of episomal vectors. Stem Cell Translational Medicine, 3(7): 787-91. # = equal last author.

Research Projects

For project inquiries, contact our research group head.



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact Senior Research Fellow Dr Raymond Wong

Department / Centre

Surgery

Unit / Centre

Cellular Reprogramming Group

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