"...we focus our studies on defining the role of regulatory pathways that control proliferation of normal, mutant and malignant hematopoietic stem and progenitor cells and apply this knowledge to develop effective cell and gene therapy for serious blood disorders, many of which remain incurable today"
For this purpose, we focus our studies on hematopoietic stem cells, because of their potential in advanced cell therapy and future gene therapy. Hematopoietic stem cells have an enormous proliferative capacity, can differentiate into all blood lineages, and can be used to repopulate the entire hematopoietic system in humans and experimental animals following blood and marrow transplantation.
The development of all blood cell types from a single stem cell (Figure: U. Blank).
Since the majority of hematopoietic stem cells residing in the bone marrow are quiescent or nondividing at any one time, it is important to understand how HSC are released from quiescence into proliferation, in order to understand the regulation of HSC fate options in vivo and to use this knowledge to develop stem cell expansion protocols ex vivo for cell and gene therapy. Therefore, we study the regulation of fate options (quiescence, proliferation, differentiation and migration) of normal hematopoietic stem cells.
We are investigating the role of known regulators to govern hematopoietic stem cell fate options and are using state-of-the-art technical approaches (siRNA libraries, functional genomics) to identify novel stem cell regulators.
Leukemic stem and progenitor cells are studied to unravel the molecular mechanisms of leukemia to allow future design of novel therapies for malignant blood disorders. The studies employ mutant mouse models as well as blood and bone marrow samples frompatients to define molecular and cellular defects in leukemia.
A key mission of the laboratory and the hematology clinic is to develop novel cell and gene therapies for malignant disorders and genetic defects in hematopoietic cells. To increase the availability of possible stem cell donors for patients with malignant blood disorders we are developing stem cell expansion protocols using umbilical cord blood. Novel therapies for genetic blood disorders are being developed using hematopoietic stem cells from patients and animal models for these disorders. Induced pluripotent stem cells derived from patients are also being used to study disease mechanisms and gene replacement therapies.
The efforts in cell and gene therapy focus on the development of permanent cure for genetic disorders of the blood system since the genetically modified cells can be transplanted back to the patient and will be expected to produce genetically corrected cells of all blood lineages.
Page Manager: Jens Forsberg
Last modified: 2010-07-30
