Isolation and characterization of Leishmania mutants defective in glycosomal protein import.

Kinetoplastid parasites contain a unique microbody organelle called the glycosome. Several important metabolic pathways found in the cytoplasm of higher eukaryotes are compartmentalized within the glycosome in these pathogens. This fundamental difference between the host and parasite has led to consideration of the glycosome as a potential chemotherapeutic target.

Cytokine mobilization of peripheral blood stem cells in patients with Gaucher disease with a view to gene therapy.

As clinical trials for gene therapy in Gaucher disease (GD) begin, questions regarding the biology of the hematopoietic stem cell in this disease remain unanswered. This study demonstrates the ability to mobilize and collect CD34+ cells in three patients with the disorder. Our RAC/FDA-approved clinical trial utilizes mobilized peripheral blood stem cells (PBSC) as the target cells for gene transfer.

Efficient retroviral mediated transfer of the glucocerebrosidase gene in CD34+ enriched umbilical cord blood human hematopoietic progenitors.

Obtaining efficient transfer of a normal gene and its sustained expression in self-renewing hematopoietic stem cell populations is a central concern for gene therapy initiatives. Potentially, 10(8) to 10(9) CD34+ enriched cells per patient will be required for transduction and subsequent reimplantation. These studies present an efficient method for the transduction of human CD34+ cells that can be used in a clinical study of gene transfer.

Long-term expression of the glucocerebrosidase gene in mouse and human hematopoietic progenitors.

Gaucher disease (GD), one of the most common inherited metabolic disorders, is an excellent candidate for gene therapy using hematopoietic stem cells as targets. Animal models have demonstrated the feasibility of introducing the human glucocerebrosidase (GC) gene into hematopoietic progenitors with long term expression using a variety of retroviral vectors. We have previously demonstrated the expression and integration of the human GC gene in mouse hematopoietic progenitors and their progeny 4-8 months post transplant in primary recipients using the retroviral vector MFG-GC.

The protein tyrosine kinase substrate cortactin is differentially expressed in murine B lymphoid tumors.

Src family protein tyrosine kinases (PTKs) actively participate in signal transduction during lymphocyte activation. However, little is known about the roles of PTKs and their substrates in lymphocyte differentiation. To identify PTK substrates that may be differentially expressed during B lymphopoiesis, we screened a panel of murine B lymphoid tumor cell lines representing various developmental stages using monoclonal antibodies (MAbs) specific for pp60src substrates.