Dr Amy Winship completed her PhD in 2016 at the Hudson Institute of Medical Research before receiving a Cancer Council Victoria Postdoctoral Fellowship to expand on her PhD studies to advance understanding of the development and progression of uterine cancer. In 2017, she relocated to the Monash Biomedicine Discovery Institute to study the importance of numerous different DNA repair pathways for maintaining oocyte (egg) quality and female fertility in response to anti-cancer treatments, environmental toxins and maternal ageing. During this time, she has been awarded an ARC DECRA and NHMRC Early Career Fellowship. Dr Winship is now a Group Leader in reproductive biology at Monash University, having advanced knowledge of endocrine and immune regulators driving ovarian, uterine or placental dysfunction leading to infertility, pregnancy loss, or pregnancy complications.
Research
Cancer therapies, like chemotherapy, can cause devastating side-effects for young female survivors, such as infertility and early menopause. Now, immunotherapies are revolutionising cancer therapy. They activate the patient’s immune system to target and kill tumour cells. Because they are so effective, patients are receiving these drugs before the full spectrum of side-effects have been tested. Since women are often excluded from clinical trials of new cancer therapies, the impacts of immunotherapies on the female reproductive and endocrine systems in particular were unknow.
Dr Winship’s research has begun to address this crucial knowledge gap; recent data have shown for the first time that immunotherapies cause an inflammatory response in the ovaries. This inflammation is damaging enough to kill the eggs stored within, which may have permanent impacts to fertility and hormone production that is necessary to support overall health in girls and women. This finding has been ground-breaking in the field because it has uncovered entirely new interactions between the immune system and the ovary, which were previously unknown.
Additionally, while the fertility preservation field has focused almost exclusively on understanding how cancer treatments damage the ovary, Dr Winship’s research team are world-leading in identifying mechanisms by which different cancer therapies can impair the uterine response to hormones, providing an additional barrier to the establishment and maintenance of healthy pregnancy for female cancer survivors.
The Al & Val Rosenstrauss Fellowship supports current studies which are focused on improving understanding of the precise causes of immunotherapy-induced ovarian damage, as well as defining the potential long-term impacts of immunotherapies on hormone levels, fertility and pregnancy. At the same time, testing will be performed to determine the efficacy of multiple different protection strategies, including tests of an existing drug that is already approved to treat inflammation.
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.
