|Associate Professor Alice Pebàyemail@example.com||+61 3 99298165||View page|
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.
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
- 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
- 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.
National Health & Medical Research Council
Australian Research Council
Friedreich Ataxia Research Alliance
Ophthalmic Research Institute of Australia
Joan and Peter Clemenger Foundation
* 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.
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.
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For further information about this research, please contact Associate Professor Alice Pebày