Research Interests
Hematopoietic and Endothelial Development
We are interested primarily in embryonic hematopoietic and endothelial development and in developmental lineal relationships between these two cell types.
In particular, we are interested in the role of the Vascular Endothelial Growth Factor (VEGF) receptor Flk-1 in the development of these two lineages. Flk-1 is known to mark the common embryonic progenitor of these two lineages, the hemangioblast, and plays a key role in the lineage determination events that underlie the origins of these cell types.
Ongoing work includes the use of gene targeting in embryonic stem (ES) cells to clarify the role of Flk-1 in embryonic hematopoiesis and endothelial development, and to facilitate the isolation and characterization of hemangioblasts.
Biology of CD109 in Hematopoietic Cells
We have recently cloned the human and murine cDNAs encoding the cell surface antigen CD109. This antigen marks very early hematopoietic stem cells with long-term reconstitution ability. And curiously, while it is not found on later progenitors or resting mature blood cells, CD109 reappears as a platelet and T cell activation antigen. Ongoing studies will elucidate the role(s) of CD109 in hematopoiesis, hemostasis and in cell-mediated immunity.
Gene Therapy of Acute Myeloblastic Leukemia (AML)
Using a murine model of AML, we are optimizing a gene therapy/tumour vaccination strategy for the control of minimal residual disease in patients with AML. Our goal is to use genetically engineered, patient-derived leukemia cell vaccines to enhance the graft-versus-leukemia effect seen after allogeneic bone marrow transplantation for AML. We anticipate that this strategy may be effective in the autologous setting as well, and therefore may provide a new therapeutic avenue to the majority of AML patients that are currently excluded from allogeneic transplantation. This strategy has been extremely successful to date in our animal model.
Related studies include the characterization of the developmental role of the blood coagulation system during embryonic and tumour angiogenesis, the isolation of novel genes expressed during embryonic hematopoiesis, and the development of a novel gene therapy approach to the treatment of hemophilia.