Single-cell technologies can provide unprecedented insights into tissue heterogeneity of normal blood and acute myeloid leukemia (AML). We monitored stress signaling in single cells to understand how hematopoietic and leukemia stem cells balance survival and apoptosis. Furthermore, we combined single-cell RNA-sequencing and genotyping to define AML cell types and their malignant properties. Uncovering principles of normal blood development and leukemia will ultimately lead to therapies that can eliminate heterogeneous AML cells.

Speaker bio:
Peter van Galen investigates fundamental mechanisms that maintain normal hematopoiesis and acute myeloid leukemia (AML). He uses innovative and single-cell technologies to study the stem cells that sustain these complex tissues, a theme that was carried forward from his Ph.D. work with Dr. John Dick (Toronto) to his postdoc with Dr. Bradley Bernstein (Boston). The first area of research focuses on hematopoietic and leukemia stem cell (HSC and LSC) maintenance during stress. He implicated the Unfolded Protein Response and Integrated Stress Response as critical pathways that control HSC and LSC fate by balancing apoptosis and survival. The second area of research focuses on transcriptional control of normal and malignant tissue hierarchies by transcription factors and epigenetic regulation. He also combined single-cell transcriptional and genetic profiling with machine learning to define malignant AML cell types, revealing disruption of regulatory networks and drivers of malignant progression. Ultimately, van Galen aims to use innovative technologies and bioinformatics to uncover the organizing principles of normal and malignant blood systems, with the goal of discovering therapies that can eliminate heterogeneous AML cells.

Sponsored by the Life Sciences Institute, Internal Medicine, and Pathology.