Juerg Schwaller is research group leader at that Department of Biomedicine of the University Hospital Basel. He holds a research professorship sponsored by the Gertrude von Meissner Foundation. The work of the “Childhood leukemia research group” aims to better understand the molecular mechanisms underlying induction and maintenance of acute leukemia a malignant disease that is characterized by accumulation of white blood cells that are blocked in differentiation with aberrant self-renewal capacity. Acute leukemia is the consequence of several functionally cooperating genetic lesions involving regulators of cellular differentiation and signaling mediators like protein kinases controlling proliferation and cell survival. There is strong evidence that similar to normal hematopoiesis, acute leukemia is hierarchically organized and driven by leukemic stem cells that are able to initiate the disease in a secondary host. Self-renewing leukemic stem cells have been proposed to be the “Achilles heel” for successful therapies, as these cells seem to be able to escape effective chemotherapy in their sanctuary niche within the bone marrow. Using a genetic approach, we have recently functionally identified PIM serine/threonine kinases as potential therapeutic targets for acute leukemia. We have characterized several small molecule PIM kinase inhibitors with in vitro anti-leukemic activity. In addition, we found that PIM1 plays an essential role for homing and migration of normal and malignant hematopoietic stem cells by interfering with the CXCL12/CXCR4 chemokine signal transduction axis. To identify and validate new therapeutic principles we are in to process to establish conditional leukemia models that allow searching for molecular and cellular targets of distinct oncogenes during induction, maintenance and potential reversibility of the disease.
Our group has close collaborations with scientists working in Basel (Antoine Peters. FMI) and groups abroad.