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My long-term research goal
is to improve the use of bone marrow transplantation for the treatment of
both malignant and non-malignant diseases. My immediate interests involve
introducing genetic modifications in hematopoietic stem cells (HSC) that
may allow for their controllable expansion in vitro or in vivo. I have used
both gene targeting to create animal models as well as in vitro differentiation
of mutant embryonic stem (ES) cells to study HSC physiology and transplantation
biology. Some of the genes studied by this method may also prove useful
in expansion of, or selective amplification or survival of other target
cells useful in transplantation, such as dendritic cells. Expansion of stem
(and/or progenitor) cells may allow more patients to receive transplants
and decrease the toxicities of transplantation by accelerating engraftment
and/or decreasing the level of conditioning (pre-transplant chemo- or radiation
therapy) required. Although I have focused on studying transplantation in
murine models, the availability of NOD/SCID mice for transplantation with
human cells allows us to transition from these murine models to testing
in human patients. Our current focus is on testing whether the transgene
I have shown to improve engraftment in murine models, a truncated erythropoietin
receptor, can also facilitate engraftment of transplanted umbilical cord
blood cells. As part of this project, we are also studying the role of this
receptor transgene on dendritic cell physiology, as well as other immunologic
cells involved in engraftment, immune reconstitution, and graft-versus-host
disease. |
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