Pamela Becker MD, PhD
University of Washington
Dr. Becker is pursuing several areas of research investigation, including 1) the mechanism of adhesion mediated chemotherapy resistance in acute myeloid leukemia and 2) hematopoietic stem cell gene transfer for a genetic disorder of DNA repair, Fanconi anemia.
Adhesion mediates chemotherapy resistance for both acute myeloid leukemia and multiple myeloma. We have performed extensive analysis of expression and function of the VLA-4 adhesion receptor by blast cells from patients with acute myeloid leukemia, and shown correlation of functional expression with overall survival. We have now undertaken a broader study of the adhesion characteristics of leukemia cells or myeloma cells, and are testing novel combinations of chemotherapy with agents that disrupt adhesion of leukemia or myeloma cells in the laboratory, with the goal of development of new clinical trials in patients. We are also examining the interaction of leukemia stem cells with the bone marrow microenvironment. In addition, we are working collaboratively on a project on erythropoietin receptor expression by multiple myeloma cells.
We are working on development of a clinical gene transfer protocol to correct hematopoietic stem cells for Fanconi aplastic anemia. Thus far, we can demonstrate functional correction using a lentiviral vector in the laboratory, for both animal models and human patient cells. Preclinical studies and preparation of regulatory documents are continuing with the goal of a clinical trial in the near future.