Novel Nanoscale Phosphoproteomic Discovery of Therapeutic Targets in AML Stem Cells
Dr. Wang has moved and will be continuing his research at City of Hope's Beckman Research Institute in Duarte, CA. http://www.leowanglab.org/
Background
Acute myeloid leukemia (AML) is difficult to treat, relapses easily, and is often fatal. This is largely due to the existence of rare leukemia stem cells (LSCs), which are able to propagate the disease but are resistant to chemotherapy. Developing therapies that specifically target LSCs will improve AML cure rates dramatically.
To eradicate AML LSCs, we need to identify how they maintain "stemness" - the ability to regenerate themselves indefinitely, unlike normal AML cells that divide a certain number of times and then die. Stemness is a feature that LSCs share with hematopoietic stem cells (HSCs), which are the blood progenitor cells responsible for differentiating into all the normal blood cells in the body over a lifetime.
Project Goals
Comparing the active pathways shared by LSCs and HSCs but absent in other AML cells will identify candidates responsible for LSC stemness; these can then be targeted to eliminate LSCs. Because proteins are the effectors of almost all cellular functions, this comparison should be done at the protein level. However, only very recently have technical advances allowed the proteomic (protein-level) analysis of rare cell populations like LSCs and HSCs. We have developed unique technologies and have expertise available nowhere else in the world, allowing us to undertake proteomic analyses of pure populations of rare cells. Using these and other advanced techniques, we will generate a unique activated proteomic signature responsible for LSC stemness, identifying candidates for further experiments in which pharmacologic interventions can be designed, tested, optimized, and developed into new leukemia cures.
