Nora Heisterkamp Lab
The Heisterkamp lab has been studying leukemia for over 30 years. Initial research focused on cell-intrinsic mechanisms of leukemia development, including how the fusion of the BCR gene to the c-ABL proto-oncogene causes Philadelphia chromosome-positive leukemias. Subsequently, the lab became interested in tackling the problem of drug resistance. This may be immediately present, or develop in the course of therapy, causing relapse.
Our current focus is on precursor B-lineage acute lymphoblastic leukemia (pre-B ALL), which develops in the bone marrow. In this location, a direct contact with non-leukemia cells stimulates pre-B ALL cell growth and provides significant protection against chemotherapy. There is an ongoing communication between these cells, and we have demonstrated that interfering with the interaction can make the pre-B ALL cells more vulnerable to eradication. Thus, one overall goal is to further define the communication in molecular terms, to enable us to more precisely intercept the signals and chemo-sensitize the leukemia cells.
We are also exploring this on a biochemical level. All cells are covered by a dense layer of carbohydrate-containing cell surface molecules including glycoproteins and glycolipids. We are determining how these specifically contribute to the reciprocal communication between the leukemia cells and their protective environment. Other opportunities to eradicate drug-resistant leukemias via cell-extrinsic mechanisms include immunotherapy. We are studying if it is possible to use normal blood NK cells which have been expanded and activated to kill pre-B ALL cells located in the bone marrow.