Project Term
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The Brigham & Women's Hospital
Boston, MA
United States
Project Summary
Our research aims to identify and exploit vulnerabilities that distinguish acute myeloid leukemia (AML) cells from healthy blood cells. We found that targeting protein translation can selectively induce apoptosis in AML cells and are working to translate this into new therapies. Using advanced single-cell sequencing, we track malignant cells across disease evolution to eliminate those that drive relapse. Our overall goal is to develop more effective treatments for patients with AML.
Lay Abstract
The Van Galen laboratory is developing new ways to treat acute myeloid leukemia (AML), a blood cancer that often returns even after treatment. Despite recent advances, AML remains difficult to cure because it consists of different leukemia cell types, some of which adapt to survive therapy and cause relapse. Our research program aims to address this issue by identifying weaknesses of AML cells that can be targeted and by helping the body’s immune system destroy AML cells more effectively.
To target leukemia cells effectively, we need to identify what sets them apart from healthy blood cells. Because there is variability between leukemia cells, we have developed technologies to track each individual cell. By sequencing the DNA and RNA of thousands of single cells per experiment, we can even detect rare leukemia cells that persist after therapy. We apply these technologies to identify new targets in cells from patients who have donated samples for research. Additionally, our research has shown that leukemia cells have specific ways of producing new proteins and responding to stress.
Our work focuses on three key projects. The first project studies how blocking a protein called eIF4A, which helps AML cells make proteins they need to survive, makes leukemia cells more vulnerable to treatment. The second project examines rare AML cells that survive therapy, using single-cell analysis technologies to uncover unique properties that may make them especially vulnerable. Finally, the third project looks at how the immune system can be harnessed to fight AML. We study the interactions between AML cells and immune cells called T cells to help them recognize and kill leukemia cells.
Together, these projects approach AML from different but connected angles, aimed at improving how AML is treated and reducing the chances of relapse. Success will be measured by identifying specific weaknesses in AML cells and immune mechanisms that enhance treatment response. Through these efforts, we hope to build a foundation for more effective therapies that lower relapse rates and improve AML outcomes.
Program
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