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Research Overview

There are currently many incurable childhood diseases, and stem cell research offers significant promise towards therapies in these conditions.

The Stem Cell Medicine Group uses the potential of stem cells to create models of eye and ear diseases in the laboratory. These models offer us a window through which to understand disease mechanisms and develop new therapeutic approaches, treatments, and cures.

Our aim is to disseminate and increase translational stem cell research and utilise the great potential of regenerative medicine.

The stem cell field of research has developed considerably in the past few years with the advent of induced pluripotent stem (iPS) cells. These are stem cells which are generated from tissues of children or adults, including blood and skin cells. We can direct the iPS cells to turn into specific cell types of the body that can form tissues and mini-organ structures – known as organoids- in the laboratory dish, a process biologists call differentiation.

Our research uses this technology to study organoids derived from a patient’s own cells, which exhibit the genetic disease of the patient. We work with organoids because they replicate aspects of normal development and provide unlimited quantities of cells for research. Organoids are also amenable to molecular and imaging approaches, providing a unique way to understand human organs. We have developed differentiation methods to generate retina, inner ear, and brain organoids from iPS cells.

Dr Anai Gonzalez Cordero leads both the Stem Cell Medicine Group and The Stem Cell and Organoid Facility.

The Stem Cell Medicine Group uses the potential of pluripotent stem cells to create laboratory models of eye and ear diseases to understand disease mechanisms and develop new therapeutic approaches. Our aim is to disseminate and increase translational stem cell research and utilise the great potential of regenerative medicine for childhood disease.

There are currently many incurable childhood diseases, and stem cell approaches offer significant promise towards developing new therapies for these conditions. The stem cell field of research has developed considerably in the last few years with the advent of iPS cells. These are stem cells which are generated from tissues of children or adults, including blood and skin cells. We can then direct the iPS cells to turn into cells that can form tissue and mini-organ structures ("organoids") in the laboratory dish, a process biologists called "differentiation", so they can be used in studies.

This technology provides us with an opportunity to study tissues derived from a patient’s own cells. We have developed differentiation methods to generate retinal and inner ear organoids from iPS cells. We work with organoids as they replicate aspects of normal development and provide unlimited quantities of cells for research. Organoids are also amenable to molecular and imaging approaches.

Dr Anai Gonzalez Cordero leads both the Stem Cell Medicine Group and The Stem Cell and Organoid Facility.

Lab Head

Anai

Anai Gonzalez Cordero

Group Leader, Stem Cell Medicine
Available for Student Supervision

Group Leader, Stem Cell Medicine and Head, Stem Cell & Organoid Facility. If you are interested in joining the Stem Cell Medicine Group or Stem Cell & Organoid Facility, please contact Dr Gonzalez Cordero directly.

View full bio

Team Members

Deborah Aubin
Deborah Aubin
Research Officer
Melissa Mangala
Melissa Mangala
Research Officer
Ben Lim 2
Ben Lim
Research Assistant
Emilie Wong
Emilie Wong
Research Assistant
Keeva Connolly
Keeva Connolly
PhD Candidate
Michelle
Michelle O'Hara-Wright
PhD Candidate

Research Projects

Our group's main areas of research involve the use of organoids to:

  • understand the development of the human retina
  • develop new bioengineering technologies to improve the differentiation and maturation of organoids
  • model retinal and inner ear genetic diseases to further our understanding of disease pathophysiology
  • develop and test new therapies for genetic conditions of the retina and inner ear.

Understanding human retinogenesis

In the lab, we are interested in using our 3D retinal organoids to understand human retinal development. Of particular interest is the development of cone photoreceptor cells and the events leading to the formation of the cone-rich macular region in the human eye.

Embryonic retinogenesis takes place in a three-dimensional environment, where various cellular, molecular, and electrophysiological cues are spatially and temporally coordinated.

More than likely, many of these cues are missing from our current in vitro system. We are using omics and bioengineering technology together to promote macular development and dissect the detailed events of human retinogenesis.

Biotechnology to improve organoid development 

We have comprehensively characterised our retinal organoids and demonstrated their utility in modelling diseases and for gene and cell therapies.

However, these culture systems still have limitations. We aim to improve culture conditions to better model the in vivo retinal niche by applying a combination of techniques that are overlooked in current culture practices.

For example, the culture of complex retinal-brain organoids promises to improve survival of retinal ganglion cells.

Cortical-retinal complex organoids: These are generated using our 2D/3D protocol. We utilise the potential of having these two organs developing in close proximity to study connections between the two organs.

We are currently investigating whether addition of electrical, and light-evoked biomimetic cues to organoid cultures enhances their development and maturation.

Modelling of retinal and otic degenerative diseases

We have a lot of expertise and experience in deriving retinal and inner ear organoids from pluripotent stem cells. These organoids mimic the in vivo human organs containing the cell populations necessary to generate a functional structure. We are interested in the cells affected in the majority of the retinal and otic diseases, the light sensing photoreceptor cells, and the mechanosensory hair cells of the inner ear.

Relatively little is known about why photoreceptor and hair cells die in many different degenerative conditions.

We seek to understand the mechanisms underlying diseases of the retina and ear as well as develop therapeutic approaches that will slow or prevent the loss of degenerative cells.

In the lab, we study two of the most common inherited retinal degenerations (IRDs), Stargardt’s macular degeneration and Usher Syndrome. The large size of these genes has hampered the development of gene therapy for these conditions. We are therefore investigating various other genetic therapies.

hIPS-derived hair cell & Virally labelled hPSC-derived retinal organoid.


Stargardt's disease

Stargardt’s disease (STGD1) is one of the most common inherited retinal diseases, with no current treatment. It is characterised by loss of light-sensing photoreceptor cells in the macular region of the eye, resulting in irreversible vision loss and blindness. STGD1 is caused by mutations in the retina-specific ATP-binding cassette transporter gene, ABCA4, which is highly expressed in photoreceptor cells.

We use retinal organoids derived from induced pluripotent stem cells (iPSCs) to recapitulate the development of the human retina and model diseases, such as Stargartd’s. We are conducting omics studies to elucidate disease toxicity specifically in photoreceptor cells. Our investigations have the potential to lead to novel pathways and treatment targets.

Usher (USH) syndrome

Mutations in more than 13 genes have been identified to cause USH, especially affecting hair cells and photoreceptors in the inner ear and retina, respectively.

However, little is known about the pathophysiology of USH syndrome, hindering the development of new therapies.

Currently no treatments are available for the retinal defect, and only a limited number of the patients can benefit from cochlear implants.

Both cell types affected during disease, the hair and photoreceptor sensory cells, share common structural features, such as cilia and ribbon synapses. In the lab, we generate iPS-derived retinal and inner ear organoids containing these cell types and these structures enable the study of USH in both organs.

The main objective of our research is to develop new therapeutic approaches for various subtypes of USH.

We are currently developing gene therapies for Usher1b, Usher1f and Usher2a.

Team Photos

Opportunities

For current opportunities in the Stem Cell team please refer to the careers page here.

Call to Honours Students!

Have you finished your degree and still passionate about science? Want to get hands on experience in the laboratory and get paid to do that?

Join the Stem Cell Medicine Group as a Research Assistant to learn all about stem cell research and organoids. Only pre-requisite is that you are passionate about science and a keen learner. You will help the group on day-to-day activities and be involved in our various projects.

Contact [email protected] with your CV for more information.

Stem Cell Academy

One week STEM work experience program during November for Year 11-12 students in Western Sydney. Applications close October 15th. Learn more here.

PhD Student Candidates

CMRI offers a competitive PhD Research Award, providing a top-up on other PhD scholarships.

Applications are open all year; more details about the application process can be found on the CMRI Research Awards page. 

For further information, contact the CMRI Postgraduate student coordinator ([email protected])

A few of the projects available include: 

  • Understanding Birdshot Uveitis using iPSC-derived microglia and organoids
  • Developing gene therapy for Usher1F disease using induced pluripotent stem cells (iPS)
  • Creating a macula in retinal organoids
  • Investigating the development of complex retinal and brain organoids

Honour Students  

Interested applicants should submit CV and Cover Letter to Dr. Anai Gonzalez-Cordero ([email protected]).

Publications

Bioelectric potential in next-generation organoids: electrical stimulation to enhance 3D structures of the Central Nervous System.

Michelle O’Hara-Wright, Sahba Mobini, Anai Gonzalez-Cordero. Frontiers in Cell and Developmental Biology. 17 May 2022; doi.org/10.3389/fcell.2022.901652.

Differentiation of brain and retinal organoids from confluent cultures of pluripotent stem cells connected by nerve-like axonal projections of optic origin.

Milan Fernando, Scott Lee, Jesse R. Wark, Di Xiao, Hani J. Kim, Grady C. Smith, Ted Wong, Erdahl T. Teber, Robin R. Ali, Pengyi Yang, Mark E. Graham, Anai Gonzalez-Cordero 2022, Stem Cell Reports; doi.org/10.1016/j.stemcr.2022.04.003.

Human iPSC-Derived Retinal Organoids and Retinal Pigment Epithelium for Novel Intronic RPGR Variant Assessment for Therapy Suitability.

Chahine Karam F, Loi TH, Ma A, Nash BM, Grigg JR, Parekh D, Riley LG, Farnsworth E, Bennetts B, Gonzalez-Cordero A, Jamieson RV. 2022, J Pers Med. 2022 Mar 21;12(3):502. doi: 10.3390/jpm12030502.

AAV-p40 bioengineering platform for variant selection based on transgene expression.

Westhaus A, Cabanes Creus M, Jonker T, Sallard E, Navarro RG, Zhu E, Baltazar G, Lee S, Wilmott P, Gonzalez-Cordero A, Santilli G, Thrasher AJ, Alexander IE, Lisowski L. 2022, Hum Gene Ther. 2022 Mar 17. doi: 10.1089/hum.2021.278.

Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids.

West EL, Majunder P, Naeem A, Fernando M, O'Hara-Wright M, Lanning E, Kloc M, Ribeiro J, Ovando-Roche P, Shum IO, Jumbu N, Sampson R, Hayes M, Bainbridge JWB, Georgiadis A, Smith AJ, Gonzalez-Cordero A, Ali RR. 2022, Stem Cell Reports. 2022 Mar 15:S2213-6711(22)00132-1. doi: 10.1016/j.stemcr.2022.02.019

Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.

Ribeiro J, Procyk CA, West EL, O'Hara-Wright M, Martins MF, Khorasani MM, Hare A, Basche M, Fernando M, Goh D, Jumbo N, Rizzi M, Powell K, Tariq M, Michaelides M, Bainbridge JWB, Smith AJ, Pearson RA, Gonzalez-Cordero A, Ali RR. 2021. Cell Reports. Apr 20;35(3):109022.

Evaluation for Retinal Therapy for RPE65 Variation Assessed in hiPSC Retinal Pigment Epithelial Cells.

Nash BM, Loi TH, Fernando M, Sabri A, Robinson J, Cheng A, Eamegdool SS, Farnsworth E, Bennetts B, Grigg JR, Chung SK, Gonzalez-Cordero A, Jamieson RV. 2021, Stem Cells International. 2021:4536382. DOI: 10.1155/2021/4536382.

Retinal organoids: a window into human retinal development.

Michelle O’Hara-Wright and Anai Gonzalez-Cordero. 2020. Development, 147: dev189746

Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina

Awais Javed, Pierre Mattar, Kamil Kruzcek, Suying Lu, Anai Gonzalez-Cordero, Magdalena Kloc, Rod Bremner, Robin R. Ali and Michel Cayouette. 2020. Development 2020 Sep 2; dev.188730.

High-Throughput In Vitro, Ex Vivo, and In Vivo Screen of Adeno-Associated Virus Vectors Based on Physical and Functional Transduction.

Adrian Westhaus, Marti Cabanes-Creus, Arkadiusz Rybicki, Grober Baltazar, Renina Gale Navarro, Erhua Zhu, Matthieu Drouyer, Maddison Knight, Razvan F. Albu, Boaz H. Ng, Predrag Kalajdzic, Magdalena Kwiatek, Kenneth Hsu, Giorgia Santilli, Wendy Gold, Belinda Kramer, Anai Gonzalez-Cordero, Adrian J. Thrasher, Ian E. Alexander, Leszek Lisowski. Hum Gene Ther. May 2020; 31(9-10): 575–589. Published online 2020 May 8. doi: 10.1089/hum.2019.264

Use of bioreactors for culturing human retinal organoids improves photoreceptor yields.

Ovando-Roche P., West EL, Branch M.J, Sampson RD, Fernando M, Munro P, Georgiadis A, Rizzi M, Kloc M, Naeem A, Ribeiro J, Smith AJ, Gonzalez-Cordero A and Ali RR. 2018. Stem Cell Research and Therapeutics, 9:156.

Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells.

Gonzalez-Cordero A, Goh D, Kruczek K, Naeem A, Fernando M, kleine Holthaus SM, Takaaki M, Blackford SJI, Kloc M, Agundez L, Sampson RD, Borooah S, Ovando-Roche P, Mehat MS, West EL, Smith AJ, Pearson RA, Ali RR. 2018. Human Gene Therapy. 29:10

Transplanted Donor- or Stem Cell-Derived Cone Photoreceptors Can Both Integrate and Undergo Material Transfer in an Environment-Dependent Manner.

Waldron PVW, Marco F, Kruczek K, Ribeiro J, Graca AB, Hippert C, Aghaizu ND, Kalargyrou A, Barber AC, Grimaldi G, Duran Y, Blackford SJI, Kloc M, Goh D, Aldunate EZ, Sampson RD, Bainbridge JWB, Smith AJ, Gonzalez-Cordero A, Sowden JC, Ali RR,and Pearson RA. 2018. Stem Cell Reports; 10(2):406-421.

Recapitulation of Human Retinal Development From Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.

Gonzalez-Cordero A, Kruczek K, Naeem A, Fernando M, Kloc M, Ribeiro J, Goh D, et al. 2017. Stem Cell Reports, 9 (3): 820–37.

Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors Into a Mouse Model of End-Stage Retinal Degeneration.

Kruczek K, Gonzalez Cordero A, Goh D, Naeem A, Jonikas M, Blackford SJI, Kloc M, et al. 2017. Stem Cell Reports; 8 (6): 1659–74.

lsolation and Comparative Transcriptome Analysis of Human Fetal and iPSC-derived Cone Photoreceptor Cells.

Welby E, Lakowski J, Di Foggia V, Budinger D, Gonzalez-Cordero A, Lun ATL, Epstein M, Patel A, Cuevas E, Kruczek K, Naeem A, Minneci F, Hubank M, Jones DT, Marioni JC, Ali RR, Sowden JC. 2017. Cells. Stem Cell Reports. 12;9(6):1898-1915.

Human Stem Cell-Derived Retinal Epithelial Cells Activate Complement via Collectin 11 in Response to Stress.

Fanelli G, Gonzalez Cordero A, Gardner PJ, Peng Q, Fernando M, Kloc M, Farrar CA, et al. 2017. Scientific Reports 7 (1).

Pluripotent stem cells and their utility in treating photoreceptor degenerations.

Aghaizu ND, Kruczek K, Gonzalez-Cordero A, Ali RR, Pearson RA. 2017. Prog Brain Res.;231:191-223.

Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors.

Pearson RA, Gonzalez-Cordero A, West EL, Ribeiro J, Aghaizu ND, Goh D, Sampson RD, Georgiadis A, Waldron PV, Duran Y, Naeem A, Kloc M, Cristante E, Kruczec K, Warre-Cornish K, Sowden JC, Smith AJ and Ali RR. 2016. Nature Communications 7,13029.

Development of an Optimized AAV2/5 Gene Therapy Vector for Leber Congenital Amaurosis Owing to Defects in RPE65.

Georgiadis, A, Duran Y, Ribeiro J, Abelleira-Hervas L, Robbie SJ, Sünkel-Laing B, Fourali S, Gonzalez-Cordero A, Cristante E, Michaelides M, Bainbridge JWB , Smith AJ and Ali RR. 2016. Gene Therapy 23 (12).

Multimodal analysis of ocular inflammation using endotoxin-induced uveitis.

Chu CJ, Gardner PJ, Liyanage SE, Gonzalez-Cordero A, kleine Holthaus SM, Copland DA, Luhmann UFO, Smith AJ, Ali RR, and Dick AD. 2016. Dis Model Mech.,1;9(4):473-81.

Cellular strategies for retinal repair by photoreceptor replacement.

Jayakody SA, Gonzalez-Cordero A, Ali RR, & Pearson RA. 2015. Progress in Retinal and Eye Research, 1–36.

An essential role for LPA signalling in telencephalon development.

Geach TJ, Faas L, Devader C, Gonzalez-Cordero A, Tabler JM, Brunsdon H, Isaacs HV and Dale L. 2014. Development, 141: 940–949.

Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina.

Gonzalez-Cordero A, West EL, Pearson RA, Duran Y, Carvalho LS, Chu CJ, Naeem A, Blackford SJI, Georgiadis A, Lakowski J, Hubank M, Smith AJ, Bainbridge JWB, Sowden JC, Ali RR. 2013. Nature Biotechnology, 31: 741–747.

Defining the integration capacity of embryonic stem cell-derived photoreceptor precursors.

Gonzalez-Cordero A, West EL, Hippert C, Osakada F, Martinez-Barbera JP, Pearson RA, Sowden JC, Takahashi M, Ali RR. 2012b. Stem cells 30: 1424–1435.

Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival.

West EL, Pearson RA, Duran Y, Gonzalez-Cordero A, Maclaren RE, Smith AJ, Sowden JC, Ali RR. 2012a. Cell Transplantation, 21: 871–887

Effective Transplantation of Photoreceptor Precursor Cells Selected Via Cell Surface Antigen Expression.

Lakowski J, Han YT, Pearson RA, Gonzalez-Cordero A, West EL, Gualdoni S, Barber AC, Hubank M, Ali RR, Sowden JC. 2011. Stem cells 29: 1391–1404.