
My
group’s research is focused on understanding of the basic biology of
human embryonic stem cells, their self-renewal and differentiation to
haematopoietic, retinal and corneal lineages. I believe very strongly
that understanding of the self-renewal mechanisms and their links to
master transcription factors is crucial for explaining the unusual cell
cycle regulation and the culture requirements for human embryonic stem
cells. My group has been one of the very few to initiate such basic
biology studies (already reported in several manuscripts in Hum. Mol.
Genet. Oncogene, J. Cell Biology and Stem Cells) and we are now in a
very strong position to pursue a large number of investigations in the
signalling and transcriptional regulation area in the next 5 years. Over
the last 4 years, we have been able to establish a very efficient model
of human ESC differentiation to haematopoietic lineages (Figure 1)
which results in long term multi-lineage haematopoietic engraftment into
immunocompromised recipients at levels higher (16.26%) than described
previously (paper was currently published by Cell Stem Cell and
accompanied by two commentaries one in Cell Stem Cell and one in Nature
Reports Stem Cells). We have also been the first group to drive the
differentiation of human ESC to corneal lineages and this was published
in the cover page of Stem Cells in May 2007 (Figure 2). Our standing in
the field has been marked by attraction of extramural funding (ca £ 2
million), 36 research publications in the last 6 years and 7 invited
reviews. 
One
of the most fascinating aspects of stem cell development in the last 2
years has been induction of pluripotency in differentiated cells. Seven
induced pluripotent stem cell lines have been now established in my lab
and are being used in various comparative studies of pluripotency and
differentiation. Most importantly we are combining this technology with
our established differentiation methods to initiate disease modelling in
patients diagnosed with Ligase IV, XLF deficiency and Fanconi anaemia.
A cornerstone of our work has been the clinical implementation of corneal stem cell therapy in patients with limbal stem cell deficiency. Work carried out in my group in collaboration with Mr Figueiredo, Dr Kolli and Dr Ahmad has resulted in definition of a GMP compatible culture system for expansion of limbal epithelial cells which can be transplanted into patients with unilateral limbal stem cell deficiency. In the last 18 months, eight patients have been transplanted successfully and have now a much 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.