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Saving sight. Changing lives.

Cellular Reprogramming

Affiliated with the University of MelbourneUniversity of Melbourne Logo

Lead Researcher: Dr Raymond C.B. Wong 


Current Research

The retina is a multilayer of cells at the back of the eye that is responsible for vision. Many degenerative diseases in the retina are characterised by a loss of retinal cells, such as the loss of the light-sensing cells – photoreceptors in retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy. These diseases affect millions of patients worldwide and cause a significant socio-economic burden on our healthcare system. Currently, there are no effective means to cure blindness once the retinal cells are lost. We must therefore, find a new approach to help restore vision in these patients. Regenerative medicine has the very real prospect of replacing the retinal cell losses and help restore vision in these patients.

The Cellular Reprogramming Unit is dedicated to better understand and develop treatment for eye diseases using cell reprogramming and stem cell technologies. We incorporate advanced techniques such as human induced pluripotent stem (iPS) cells, CRISPR/Cas9 gene editing and single cell transcriptomics in our research, with the goal to better understand and control cell fate decisions in the eye. This allow us to develop new ways to generate human retinal cells in the lab which can be used to study the mechanism underlying retinal diseases, tissue engineering and ultimately, transplantation.

The research focus of this laboratory is:

1. Using cell reprogramming to develop therapy to regenerate photoreceptors
2. Understanding the genetic signals that define retinal cell identity
3. Develop new cell reprogramming methods and new biomaterials to generate human stem cells and neural/retinal cells
4. Using stem cells to generate disease model to better understand eye diseases

 

Representative results of single cell transcriptome analysis and stem cell culture in Cellular Reprogramming Unit

 

 

 

 

 

 

 

 

 

Selected Appointments/Awards/Fellowships

2008 CIRM Post-doctoral Training Fellowship, California Institute for Regenerative Medicine, USA

2011 NIH Visiting Fellow Award, National Institutes of Health, USA

2013 Cranbourne Fellowship, Peggy & Leslie Cranbourne Foundation, Australia

2015 ACES-SVHM Bionics Award for Excellence in iPSC Modelling, ARC Centre of Excellence for Science & St Vincent’s Hospital, Australia

2016 MAWA fellowship, Medical Advances Without Animals Trust, Australia

2017 Guest Professor, Chief iPS cell Consultant, Department of Cornea, Shenzhen Eye Hospital, China

 

Selected research output (last 5 years)

Patent

Pebay, A., Hewitt, A., Crombie, D., Liang, H., Wong, R., Daniszewski, M., Zalivani M. (2018) Automated system for maintenance and differentiation of cells, US 2018/0282682 A1

Stem cells & cell reprogramming

1. Fang, L., Wazan, L., Tan, C., Nguyen, T., Hung, S., Hewitt, A., Wong, R. (2018) Potentials of cellular reprogramming as a novel strategy for regenerative medicine. Frontiers in Cellular Neuroscience, 2018 Nov 30; 12:460. (5 yr IF = 4.915)

2. Fang, L., Ding, Y., Liang, H., Wong, R. (2018) Using cellular reprogramming technology and induced pluripotent stem cells to study and treat retinal diseases. Chinese Journal of Experimental Ophthalmology, 36 (11).

3. Galloway, C., Dalvi, S., Hung, S., MacDonald, L., Latchney, L., Wong, R., Guymer, R., Mackey, D., Williams, D., Chung, M., Gamm, D., Pebay, A., Hewitt, A., Singh, R. (2017) Drusen in patient-derived hiPSC-RPE models of macular dystrophies.
Proceedings of the National Academy of Sciences – USA, accepted 2017.08.08 (5 yr IF = 10.359)

4. Nguyen, T., Wong, R. (2017) Neuroregeneration using in vivo cellular reprogramming. Neural Regeneration Research, 12(7): 1073-1074 (IF = 2.234)

5. Wong, R., Hung, S., Jackson, S., Singh, V., Khan, S., Liang, H., Kearns, L., Nguyen, T., Conquest, A., Daniszewski, M., Hewitt, A., Pébay, A. (2017) Generation of a human induced pluripotent stem cell line CERAi001-A-6 using episomal vectors. Stem Cell Research, 22(2017): 13-15 (5 yr IF =2.929)

6. Wong, R., Lim, S., Hung, S., Jackson, S., Khan, S., Van Bergen, N., De Smit, E., Liang, H., Kearns, L., Clarke, L., Mackey, D., Hewitt, A., Trounce, I., Pebay, A. (2017) Mitochondrial replacement in an iPSC model of Leber’s Hereditary Optic Neuropathy, Aging, 9(4):1341-1350 (5 yr IF = 5.437)

7. Hung, S., Khan, S., Lo, C., Hewitt, A., Wong, R. (2017) Drug discovery using induced pluripotent stem cell models of neurodegenerative and ocular diseases. Pharmacology and Therapeutics, pii: S0163-7258(17)30040-2. (5 yr IF = 10.562)

8. Gill, K.*, Hung, S.*, Sharov, A., Lo, C., Needham, K., Lidgerwood, G., Jackson, S., Crombie, D., Nayagam, B., Cook, A., Hewitt, A., Pébay, A.#, Wong, R.# (2016) Enriched retinal ganglion cells derived from human embryonic stem cells. Scientific Reports, 2016 Aug 10;6:30552. # = equal last author. (5 yr IF = 4.609)

9. 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, 8(5):945-57 (5 yr IF = 5.437)

10. 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, 37(33):2586-90 (IF = 23.425)

11. 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 (5 yr IF = 23.799)

12. 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, 12(2):179-88 (5 yr IF = 3.396)

13. 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). (5 yr IF = 1.677)

14. 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 Cells Translational Medicine, 3(7): 787-91. # = equal last author. (5 yr IF = 5.144)

CRISPR technologies

15. Tran, M., Khalid, M., Pebay, A., Cook, A., Lian, H., Wong, R., Craig, J., Liu, G.S., Hung, S., Hewitt, A. (2019) Screening of CRISPR/Cas base editors to target the AMD high-risk Y402H complement factor H variant, Molecular Vision, accepted 2019 Feb 18. (5 yr IF = 2.336)

16. Fang, L.*, Hung, S.*, Yek, J., Nguyen, T., Khan, S., Hewitt, A., Wong, R. (2018) A simple cloning-free method to efficiently induce gene expression using CRISPR/Cas9. Molecular Therapy -Nucleic Acids, 14: 184-191, Mar 01, 2019. (5 yr IF = 5.882)

17. Hung, S., Chrysostomou, V., Li, F., Lim, J., Wang, J.H., Powell, J., Tu, L., Daniszewski, M., Lo, C., Wong, R., Crowston, J., Pébay, A., King, A., Bui, B., Liu, G.S., Hewitt, A. (2016) AAV-mediated CRISPR/Cas gene editing of retinal cells in vivo. Investigative Ophthalmology & Visual Science, 57(7):3470-6 (5 yr IF = 3.731)

Biomaterials

18. Wang, P.Y., Khan, S., Nguyen, T., Kingshott, P., Wong, R. (2018) Topographical modulation of pluripotency and differentiation of human embryonic stem cells. IEEE Transactions on Nanotechnology, 17(3), May 2018, 381-384 (IF = 2.857)

19. Wang, P.Y., Ding, S., Sumer, H., Wong, R., Kingshott, P. (2017) Heterogeneity of mesenchymal and pluripotent stem cell populations grown on nanogroves and nanopillars. Journal of Materials Chemistry B, 5, 7927-7938. (5 yr IF = 4.959)

20. Wang, P.Y., Hung, S., Thissen, H., Kingshott, P., Wong, R. (2016) Binary colloidal crystals (BCCs) as a feeder-free system to generate human induced pluripotent stem cells (hiPSCs). Scientific Reports, 2016 Nov 11;6:36845 (5 yr IF = 4.609)

Single cell transcriptomics

21. Lukowski, S*, Lo, C.*, Sharov, A., Nguyen, Q., Fang, L., Hung, s., Nguyen, T., Senabouth, A., Jabbari, J., Welby, E., Sowden, J., Waugh, H., Mackey, A., Pollock, G., Lamb, T., Wang, P.Y., Hewitt, A., Powell, J.#, Wong, R.# (2018) Generation of human neural retina transcriptome atlas by single cell RNA sequencing. BioRxiv, 425223, # = equal last author