2009-2010 Sabbatical fellow at Centro de Investigacion Principe Felipe, Spain
2008-2009 Reader in Stem Cell Biology, Newcastle University
2004–2008 Senior Lecturer in Stem Cell Biology, Newcastle University
2003–2004 Lecturer in Stem Cell Biology, Newcastle University
1998–2003 Senior Research Associate, Department of Biological Sciences, Durham University
1994–1998 Junior Research Associate, Department of Human Genetics, Newcastle University
Dr. Carla Mellough
Dr. Irina Neganova
Dr. Joseph Collin
Dr. Nicola Hunt
Dr. Min Yu
Dr. Sanja Bojic
Dr. Dean Hallam
Dr. Birthe Dorgau
Dr. Lili Zhu
Dr. Georgios Anyfantis
Mr. Dario Melguzo (PhD student)
Mr. Shibo Jin (PhD student)
Ms. Ellie Meader (PhD student)
Mrs. Taty Kamarudin (PhD student)
Mr. Majed Falemban (PhD student)
Ms. Valeria Chichagova (PhD student)
My research group works on human pluripotent stem cells. Our aims are to understand and define the early events occurring in human embryogenesis with special focus on eye formation and developing new treatments for eye disease. We are engaged in several large research programmes that aim to define good manufacturing protocols for deriving functional corneal and retinal cells that can be used for drug testing, disease modelling and cell based replacement therapies.
This is largely facilitated by our expertise in the derivation of human pluripotent stem cells. We were one of the first groups in the UK to derive and fully characterise human embryonic stem cells (hESCs) in 2003, and these were the first to be deposited in the UK Stem Cell Bank. Our contribution to this field has been consolidated by a large awards to our group (€ 2.2 M) from the Innovative Medicines 1 Initiative (European Community) which has enabled us to establish induced pluripotent stem cell (iPSC) lines from a large number of patients (300+) with neurodegenerative diseases. Moreover we have expanded a number of these cell lines for deposition in the European Bank of induced Pluripotent Stem Cells. We have performed a large number of molecular and disease modelling studies with the aim of better understanding the role of pluripotency factors and signaling pathways and how these underpin the maintenance of pluripotent phenotype, stem cell renewal and maintenance of genomic stability.
A cornerstone of our work has been the clinical implementation of stem cell therapy in patients with total and severe limbal stem cell deficiency. Work carried out in my group in collaboration with Prof. Figueiredo has resulted in the development of a GMP compatible culture system for expansion of limbal epithelial cells which have been transplanted into patients with unilateral limbal stem cell deficiency. In the last eight years, 33 patients have been transplanted successfully and now have a greatly improved vision and quality of life. This is the first example of corneal transplantations in the UK carried out in the absence of any animal derived ingredients. In parallel to this program, my group has been pursuing differentiation of human pluripotent stem cells to rod and cone photoreceptors and retinal pigmented epithelial (RPE) cells using GMP compatible protocols. We have established an efficient differentiation system that results in formation of optic cup structures which undergo further differentiation to laminated neural retina containing all the retinal cell types. Our current research programme funded by ERC, Fight for Sight UK, Macular Disease Society UK and RPFB UK is focused on making this differentiation applicable and efficient in a large range of pluripotent stem cells. In collaboration with the human developmental biology resource (HDBR) we have started to investigate expression of key transcription factors that govern human eye formation which provides for us a golden and unprecedented platform to compare and guide our stem cell differentiation studies.
Using our iPSC expertise, we have been able to establish iPSC from patients suffering from both retinitis pigmentosa and AMD and moreover we intend to correct the faulty genes in these iPSC using Crispr/Cas9 technology. With the same technology we are currently targeting reporter genes to key retinal factors that control rod and cone commitment, thus enabling us to track their emergence during differentiation process and initiate studies of their transcriptome and proteome. In collaboration with Mr. Steel, we are developing new tools for delivering RPE and photoreceptors cells with high viability into degenerate retina as well as taking part in a multi-centre phase I/II clinical trial aiming at treating Stargard’t patients with hESC derived RPE cells.