Stem Cell Medicine

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.

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.

A pipeline of gene editing treatments designed specifically for several genetically-confirmed Australian patients with Stargardt’s and Usher2a syndromes will be developed at Children’s Medical Research Institute and tested in organoids. The overall outcome of this Fellowship will be the generation of data that facilitates the process toward clinical trial applications. A long-term vision is the follow-up testing of clinical grade Good Manufacturing Practice (GMP) produced vectors – a pre-requisite for eye gene therapy clinical programs.

Vision Loss Priority Setting Partnership (PSP)

The Stem Cell Medicine Group is currently running a Vision Loss Priority Setting Partnership (PSP) in collaboration with the Behavioural Science Unit at UNSW and the University of Sydney. If you would like to learn more and how you could participate, visit this page.

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 10-12 students in Western Sydney. Annual applications close October September and open in August. 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])

Honour Students  

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

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