Dr Gonzalez Cordero is Group Leader of the Stem Cell Medicine Group and Head of the Stem Cell & Organoid Facility at Children’s Medical Research Institute (CMRI) and Senior Lecturer at The University of Sydney, Faculty of Medicine and Health. Dr Gonzalez Cordero joined CMRI in 2019 from University College London (UCL). Her Wellcome Trust-funded Developmental and Stem Cell Biology PhD in ophthalmology and stem cell therapies from the UCL Institute of Ophthalmology established proof of concept for the feasibility of stem cell therapy for retinal disease, by transplantation of stem cell-derived photoreceptor cells.
Dr Gonzalez Cordero also heads the Stem Cell and Organoid Facility at CMRI, a service-based facility where her team works closely with scientists across Australia to develop various stem cell-derived human organoid models for research. The Facility has developed neural, cardiac, kidney and lung organoids and is actively enhancing stem cell and translational research in New South Wales and Australia.
Research
Dr Gonzalez Cordero’s research combines stem cell technologies, human organoids (mini-organs derived from pluripotent stem cells), and advanced therapeutic techniques, to treat blindness. Her group uses 3D retinal organoids to investigate two therapeutic avenues. Firstly, her team reprogrammes patient somatic cells, skin or blood cells which are directed to form induced pluripotent stem cells (iPSCs). The iPSCs are then differentiated into retinal organoids that mimic the patient’s disease in the dish. The retinal organoids are used to investigate disease pathophysiology and develop new genetic treatments for some of the most common inherited retinal conditions. Secondly, 3D organoids derived from healthy individuals are used as a renewable source of healthy human photoreceptor cells for testing novel cell replacement therapies for eye disease.
The differentiation of stem cells into retinal organoids has been transformative – providing the ability to generate photoreceptors in the laboratory that closely resemble the in vivo counterparts.
The majority of inherited retinal diseases affect the tissue at the back of the eye – the retina. The photoreceptor cells that reside in the retina and sense light, are affected in a great number of disorders, leading to vision impairment and eventually total blindness. There is an unmet need for curative treatment for millions of people worldwide living with severe eye diseases.
The Al & Val Rosenstrauss Fellowship supports the development of genetic therapies for two of the most common retinal inherited retinal diseases, Stargardt’s and Usher2a syndrome. Dr Gonzalez Cordero and team aim to correct disease causing mutations in these diseases by editing (correcting) the genetic error at its source, using CRISPR gene editing technology. This machinery will be delivered into the stem cell-derived mini retina in the dish, i.e., the patients’ retinal organoids, using a specialised delivery mechanism called a vector. As the organoids are generated from induced pluripotent stem cells (iPSCs) which in turn come from patients’ own blood cells, the retinal organoids will contain the patients’ genetic make-up and their disease characteristics – a near-perfect model in which to test these new treatments.
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.