Fanconi Hope-Sponsored Research
|Fanconi Hope is pleased to announce the award of a £20,000 research grant to Dr Ketan J Patel, MD, PhD, from the Laboratory of Molecular Biology, Cambridge University towards his ongoing work on a research project entitled: Reconstituting and Dissecting Monoubiquitination in the FA Tumor Suppressor Pathway.
Dr Patel, who is recognised as a world expert in molecular research related to Fanconi Anaemia, is being funded in this research programme by the US Fanconi Anaemia Research Fund (FARF). Fanconi Hope’s contribution to this funding represents a significant proportion of the total required over the next year and demonstrates our commitment to support key FA researchers in the UK
Fanconi Hope, in collaboration with the Fanconi Anemia Research Fundin the USA, helped fund this research project with a grant of August 2010 with a grant of £42,000. Subsequent to this Prof Lako was able to secure additional funding from another UK source to continue this line of research and is in the process of securing further funds from a 3rd source to move to the next phase of her work .Using iPSC Technology to Understand Early Haematopoietic Development in FA Patients
This is a collaborative study by Prof Majilinda Lako, PhD., Institute of Human Genetics, NE Stem Cell Institute, Newcastle University and Prof Christopher Mathew, PhD., Division of Medical and Molecular Genetics, Guys and St. Thomas Hospital, London to produce ‘induced pluripotent stem cells’ derived from patients with FANCA, FANCC, FANCG and FANCD2 to compare with cells derived from unaffected patients in order to understand better the role of FA genes in the development of blood-producing cells.
If successful, this project would help the research community:
Prof Majlinda Lako’s research group is focused on understanding of the basic biology of human embryonic stem cells (ESCs) and iPSC, their self-renewal and the efficient differentiation of the human ESCs to haematopoietic lineages. The skills acquired during the course of recent studies (DNA repair and oxidative stress measurements) are of direct relevance to this proposal and are central to the successful execution of this project.
Why is a new approach needed?
Plan of investigation.
A. Generation and characterisation of iPSC lines from FA patients.
Because of the effort involved in derivation and characterisation of iPSC lines, the initial focus will be on making iPSC lines from 2 FANCA, 2 FANCG, 2 FANCC and 2 FANCD2 patients.
B. Investigation of DNA damage response, radiosensitivity and genomic stability in control and FA patient derived iPSC lines.
It has been shown that cells lacking FANCD2, FANCC, FANCG and FANCA are more susceptible to DNA damage and to drugs that induce DNA interstrand cross-links. To investigate whether this occurs in iPSC lines derived from FA patients, various assays will be carried out in relation to:
C. Investigation of the haematopoietic differentiation of iPSC lines from unaffected controls and FA patients.
Deficiencies in any of the genes involved in the FA pathways impair haematopoietic stem cell expansion, but the effects of any of these genes during the ontogeny of haematopoiesis (alternative phrase required!) has not been addressed.