Research Interests
It is generally accepted that gene therapy holds great promise for the treatment of certain genetic disorders but that a number of important problems remain. We have been at the forefront in the design of gene therapy vectors for many years. We reported the first long term correction of a genetic disease (erythropoietic protoporphyria) by gene therapy in an animal model in the absence of spontaneous selection for transduced cells. (Pawliuk et al, Nat Med 1999 ). A major undertaking of the laboratory is the design of safe and effective lentiviral vectors capable of achieving long term correction of sickle cell disease and beta-thalassemia, the most prevalent genetic diseases worldwide.
Our model serves as one of the most interesting paradigms in the field of gene therapy because of the complexity of the genetic structures to be transferred into hematopoietic stem cells (HSCs) to achieve high, regulated beta-globin gene expression restricted to the red blood cell lineage. We have reported the long term correction of these diseases in mouse models (Pawliuk et al, Science 2001; Imren et al, PNAS 2002) and are now working to find ways to prevent potential adverse events in human HSCs that include oncogenesis by insertional mutagenesis (Hacein-Bey-Abina et al, Science 2003 ). Our work on the beta-hemoglobinopathies has recently led to the first worldwide approval of a Phase I/II human clinical trial utilizing a lentiviral vector for the gene therapy of a genetic disease.
Our laboratory is also interested in novel gene transfer approaches to HSCs (eg, integrases and transposases) and in the control of somatic cell expansion by “reversible immortalization” mediated by site specific recombination (Kobayashi et al, Science 2000; Narushima et al, Nat Biotechnol 2005). Finally, our gene transfer vectors can effectively contribute to the identification of gene-phenotype correlations in functional genomics, as we recently reported in the field of angiogenesis (Eriksson et al, Cancer Cell 2002; Cao et al, Nat Med 2003 ).
Affiliations
Leboulch Harvard Biological and Biomedical sciences page |
Philippe Leboulch, MD
Associate Professor of Medicine
NRB 0466C
(617) 525-4740
pleboulch@rics.bwh.harvard.edu
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