Regulation of stem-cell mediated host immunity by the sphingolipid pathway

Changes in the functioning of the human immune system are the main cause for many diseases, including auto-immunity, infections, and cancer. Research suggests that the sphingolipid pathway plays an important role in hematopoietic stem cell functions and, as a consequence, in the generation of mature immune cells and the functioning of the surrounding environment. This project uses advanced molecular biology and genetic methods with human cells and genetically engineered mice to examine how the human immune system develops from hematopoietic stem cells and how host immunity is established. It will also explore day/night cycles that influence the functioning of the immune system in order to decipher the mechanism controlling different host immunity responses and mortality rates from bacterial infections induced in the afternoon (high mortality) and at midnight (low mortality).

This research has the potential to contribute to our understanding of the immune system and to advancements in the treatment of patients. Other positive impacts can include optimized methods to generate immune cells for cell transplantation, better drugs to treat diseases that involve abnormal immune cell functioning, and better methods to time the delivery of drugs in order to achieve maximum effect.

The project is led in Canada by the University Health Network and the University of Toronto, in collaboration with the Weizmann Institute (Israel) and the Oncology Hospital of the Instituto Mexicano del Seguro Social (Mexico). It is funded through the second research competition of the Joint Canada-Israel Health Research Program, a partnership between Canada’s International Development Research Centre, the Canadian Institutes for Health Research, the Israel Science Foundation and the Azrieli Foundation. This 7-year, $35M Canadian-Israeli effort draws on the unique scientific strengths of both countries and facilitates networking opportunities with peers from Africa, Asia, and Latin America. Projects include a plan for integrating researchers from low- and middle-income countries that will establish long-term scientific relationships.