Neuroregeneration

Research Overview

Neuroregeneration focuses on the study of stem cells for modelling diseases, aspects of development and regeneration.

The extreme difficulty in obtaining ocular tissue from living people currently represents a major barrier to developing new treatments for blinding disease. Recent breakthroughs in stem cell technology have led to the ability to generate stem cells from adult tissue, and these “induced pluripotent stem cells” (iPSCs) now represent a powerful disease modelling tool. Generating iPSCs directly from patients allows cells to be differentiated into specific cells of interest for disease modelling, drug screening, and understanding of fundamental pathogenic mechanisms.

We have the established techniques and methodologies to efficiently generate patient-specific retinal pigment epithelium cells, which are dysfunctional in age-related macular degeneration (AMD) and inherited retinal dystrophies, as well as retinal ganglion cells, which are affected in glaucoma and other optic neuropathies. We are now modelling these ocular conditions in a dish, using iPSCs derived from specific patients in order to establish the molecular events leading to disease progression. We are also studying the cellular mechanisms involved in the genetic disease Friedreich Ataxia.                                                                                                                                                                                                                                                                                                                      

We are using gene editing technology for correction of monogenic diseases of the retina and the optic nerve. The CRISPR system is used by bacteria to counter viral intrusion and has recently been adapted to allow efficient editing of the mammalian nuclear genome. CRISPR-based technology is being heralded as a relatively straightforward technology for in vitro correction of genetic mutations in patient-specific cells and is particularly attractive for treating inherited diseases caused by genes with very specific spatial and stoichiometric expression, such as those found in many of the retinal dystrophies. We are using our unique cohort of patients with distinct monogenic inherited retinal dystrophies and iPSC technology to directly study the utility of genomic editing and correction.                                                                                                                                                                                                                                                                                                                     

Finally, human pluripotent stem cells provide an invaluable tool to study early developmental processes and the fundamental aspects of cell fate. Their manipulation towards differentiation into chosen cell types provides a powerful in vitro system to investigate the mechanisms involved in pluripotency and differentiation.

The study of lipids, or lipidomics, is an emerging and exciting area of biological science. Our laboratory dissects the roles of specific bioactive lipids in pluripotency and differentiation.

Staff

Alison Conquest, Research Assistant

Tejal Kulkarni, Research Assistant

Sandy Hung, Research Fellow

Duncan Crombie, Research Fellow

Damian Hernandez, Research fellow

Grace Liderwood, PhD Student

Maciej Daniszewski, PhD student

Collaborators

National

- Assoc. Prof. Alex Hewitt,  CERA

- Prof. Robyn Guymer,CERA

-Assoc. Prof. Mirella Dottori, University of Melbourne

-Dr. Max Lim, St Vincent Institute

-Robyn Jamieson, MRCI

International

- Stem Cell Biology & Tissue Engineering Institute for Integrated Cell-Material Sciences, Kyoto University, Japan.

-Lpath Inc., San Diego, USA.

-RaNA therapeutics, Boston, USA.

- Prof. Andrew Morris, University of Kentucky, USA.

Funding

National Health & Medical Research Council

Australian Research Council

Friedreich Ataxia Research Alliance

Ophthalmic Research Institute of Australia

Retina Australia

Joan and Peter Clemenger Foundation

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

* Co-senior  authors.

McCaughey T*, Sanfilippo PG*, Gooden GEC*, Budden DM, Fan L, Fenwick E, Rees G, MacGregor C, Craig JE, Si L, Chen C, Liang HH, Baldwin T, Pébay A*, Hewitt AW* (2016). A global social media survey of attitudes to human genome editing. Cell Stem Cell. 18 (5).

McCaughey T, Liang HL, Chen C, Fenwick E, Rees G, Wong RCB, Vickers JC, Summers MJ, MacGregor C, Craig JE, Munsie M, Pébay A*, Hewitt AW* (2016). An Interactive Multimedia Approach to Improving Informed Consent for Induced Pluripotent Stem Cell Research. Cell Stem Cell. 18 (3): 307-308.

Lidgerwood GE, Ali R, Lim SY, Crombie DE, Gill KP, Hernández D, Kie J, Conquest A, Waugh HS, Wong RCB, Liang HH, Hewitt AW*, Davidson KC*, Pébay A* (2016). Defined medium conditions for the induction and expansion of human induced pluripotent stem cell-derived retinal pigment epithelium. Stem Cell Reviews and Reports. In press, accepted 31.10.15.

Crombie DE, Van Bergen N, Davidson KC, Anjomani Virmouni S, Mckelvie PA, Chrysostomou V, Conquest A, Corben LA, Pook MA, Kulkani T, Trounce I, Pera MF, Delatycki MB, Pébay A (2015). Characterization of the retinal pigment epithelium in Friedreich ataxia. Biochemistry and Biophysics Reports. 1(4): 141-147.

Crack PJ, Zhang M, Morganti-Kossmann MC, Morris A, Wojciak JM, Fleming JK, Karve I, Wright D, Sahindranath M, Goldshmit Y, Conquest A, Daglas M, Johnston LA, Medcalf RL, Sabbadini RS and Pébay A (2014). Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes. Journal of Neuroinflammation 11(1): 37.

Frisca F, Crombie DE, Dottori M, Goldshmit Y and Pébay A (2013). The Rho/ROCK pathway is essential to the expansion, differentiation and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid. Journal of Lipid Research 54(5): 1192-1206.

Goldshmit Y, Matteo R, Sztal T, Ellett F, Frisca F, Moreno K, Crombie D, Lieschke GJ, Currie PD, Sabbadini RA and Pébay A (2012). Blockage of lysophosphatidic acid signalling improves spinal cord injury outcomes. American Journal of Pathology 181(3): 978-992.

Selected reviews

Crombie DE, Pera MF, Delatycki MB and Pébay A (2016). Using Human Pluripotent Stem Cells to Study Friedreich Ataxia Cardiomyopathy. International Journal of Cardiology 212: 37-43.

Gill KP, Hewitt AH, Davidson KC, Pébay A and Wong RCB (2014). Methods of retinal ganglion cell differentiation from pluripotent stem cells. Translational Vision Science & Technology 3(4): 1-13.

Davidson KC, Guymer RH, Pera MF and Pébay A (2014). Human pluripotent stem cell strategies for age-related macular degeneration. Optometry & Vision Science 91(8): 887-93.

Selected edited book

Stem Cell Biology and Regenerative Medicine, Regenerative Biology of the Eye. Humana Press. Pébay & Turksen Editors. May 2014.

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact Associate Professor Alice Pébay

Department / Centre

Surgery

Unit / Centre

Neuroregeneration