One goal of Professor Bouhassira's research is to learn how to produce large amounts of therapeutically useful cells with an adult phenotype by forced differentiation of human embryonic stem cells (hESC) or induced pluripotent stem cells (iPS). Dr. Bouhassira's lab has chosen the erythroid lineage as a model because it has two unique advantages as a translational target: red cells don't express the HLA genes, eliminating most of the histocompatibility issues, and red cells are enucleated and therefore cannot cause cancer. Industrial production of red cells would be of great significance because while current supplies are very safe, they remain vulnerable to new pathogens, and local shortages occur in many parts of the world.
Another goal of Dr. Bouhassira research is to develop techniques to reprogram somatic cells into iPS from patients with hemoglobinopathies, to then correct the genetic mutations in these cells, and to differentiate them into transplantable hematopoietic stem cells. One current problem is the lack of an assay to assess the quality of the iPS to ascertain that they are fully reprogrammed. To address this question, the Bouhassira lab is using tiling arrays and massively-parallel sequencing to assess the epigenetic status of iPS and of cells differentiated from hESC or iPS.
A major problem in the stem cell field is that cells obtained from hESC or iPS have embryonic phenotypes and are not functionally equivalent to adult cells. To solve that issue the Bouhassira lab is studying the epigenetic mechanisms that control gene transcription and differentiation in mammalians cells. A large effort is underway to produce genomewide maps of primary transcripts, replication timing, DNA methylation and histone modifications in undifferentiated and differentiated hESC and iPS and in their in vivo produced counterparts at different stages of development. Bioinformatics tools to analyze and integrate this data are also being developed.
Kiprilov, E.N., Awan, A., Desprat, R., Velho, M., Anne, C.A., Byskov, G., Andersen, C.Y., Satir, P., Bouhassira, E.E., Christensen, S.T., Hirsch, R.E. (2008). Human Embryonic Stem Cells in Culture Possess Primary Cilia with Hedgehog Signaling Machinery. Journal of Cell Biology 10; 180(5):897-904.
Qiu, C., Olivier, E.N., Velho, M., Bouhassira, E.E. (2008). Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human ES cells. Blood. 111(4):2400-8.
Olivier EN, Qiu C, Velho M, Hirsch RE, Bouhassira EE (2006). Large scale production of embryonic red blood cells from human embryonic stem cells. Exp Hematol. 2006 Dec; 34 (12):1635-42.