Stem Cell Medicine
We focus on two complementary fields: stem cell research and regenerative medicine.
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 differentiation of human iPS cells into retinal and inner ear organoids to understand the development of the human retina and to model diseases.
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 humans. 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. Adding cultures with molecular, electrical, and light-evoked cues to the cultures may increase the utility of the in vitro system in dissecting the detailed events in human retinogenesis.
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. The approaches we are using include gene therapy and gene editing technologies.
Our projects in this area aim to investigate the pathophysiology of USH syndrome using iPS cells and thus improve our understanding of USH syndrome. Mutations in over 13 genes have been identified to cause USH, especially affecting sensory hair cells and photoreceptors in the inner ear and retina, respectively. The lack of animal models that faithfully replicate the human pathology means that little is known about its pathophysiology and the mechanism of cellular degeneration, 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. Hair and photoreceptor sensory cells share common structural features, such as cilia and ribbon synapses, and the USH syndromes can therefore be regarded as diseases of cilia ("ciliopathies").
The main objectives of our research are to characterise both retinal and inner ear USH iPS-derived organoids to investigate disease physiology and most importantly to develop new therapeutic approaches, such as gene therapies.
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.
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