Stem Cell Medicine
We focus on two complementary fields: stem cell research and regenerative medicine.
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.
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.
Our group's main areas of research involve the use of organoids to:
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.
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.
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 (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.
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.
For current opportunities in the Stem Cell team please refer to the careers page here.
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.
One week STEM work experience program during November for Year 11-12 students in Western Sydney. Applications close October 15th. Learn more here.
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:
Interested applicants should submit CV and Cover Letter to Dr. Anai Gonzalez-Cordero ([email protected]).
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.
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.
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.
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.
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
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.
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.
Michelle O’Hara-Wright and Anai Gonzalez-Cordero. 2020. Development, 147: dev189746
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.
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
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.
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
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.
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.
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.
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.
Fanelli G, Gonzalez Cordero A, Gardner PJ, Peng Q, Fernando M, Kloc M, Farrar CA, et al. 2017. Scientific Reports 7 (1).
Aghaizu ND, Kruczek K, Gonzalez-Cordero A, Ali RR, Pearson RA. 2017. Prog Brain Res.;231:191-223.
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.
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).
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.
Jayakody SA, Gonzalez-Cordero A, Ali RR, & Pearson RA. 2015. Progress in Retinal and Eye Research, 1–36.
Lakowski J, Gonzalez-Cordero A, West EL, et al. 2015. Stem Cells, 33(8), 2469–2482.
Geach TJ, Faas L, Devader C, Gonzalez-Cordero A, Tabler JM, Brunsdon H, Isaacs HV and Dale L. 2014. Development, 141: 940–949.
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.
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.
West EL, Pearson RA, Duran Y, Gonzalez-Cordero A, Maclaren RE, Smith AJ, Sowden JC, Ali RR. 2012a. Cell Transplantation, 21: 871–887
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.