Hematopoietic stem and progenitor cells (HSPCs) maintain hematopoietic homeostasis by continuously producing the precise numbers and types of blood and immune cells, while rapidly responding to bleeding, infection, injury, and disease. Our research integrates quantitative single-cell and systems biology approaches to identify critical cell fate transitions and uncover the regulatory genes that control these processes.
1. Investigating regulatory mechanisms through cellular heterogeneity
Heterogeneity in blood and immune cell production among individual HSPCs presents an exciting opportunity to uncover the molecular mechanisms driving this variability. We have shown that hematopoietic stem cells (HSCs) from the same clone produce similar amounts of immune cells across different recipients, highlighting the importance of cell-intrinsic regulation. Using clonal tracking and single cell analysis, we are investigating novel regulatory mechanisms that quantitatively govern hematopoiesis by leveraging cell-cell variability.
2. Exploring cell-cell spatial interactions and signal transduction
While cell identity, spatial organization, and interactions are well characterized in most tissues, little is known about the spatial arrangement and dynamic interactions of cells within the bone marrow, where blood and immune cells are continuously regenerated. These spatial interactions shape cell fate decisions during hematopoiesis by dictating each cell’s exposure to external signals. To address this critical knowledge gap, we are investigating the mechanisms and functional consequences of cell-cell interactions in the bone marrow.
3. Tracking the temporal dynamics of heterogeneous hematopoiesis
Tissue formation, repair, regeneration, and aging are dynamic processes that unfold over time. Understanding their temporal dynamics is essential for uncovering how cells, signals, and regulatory mechanisms work together to maintain tissue size and function. We are investigating how cellular heterogeneity and dynamics evolve across various time scales, providing insights into the plasticity, adaptability, and resilience of hematopoiesis.
4. Targeting cellular heterogeneity and coordination in disease
Cellular heterogeneity poses significant challenges for disease diagnosis and treatment. Building on our research on cellular heterogeneity and coordination in hematopoiesis, we are developing engineering and translational strategies to improve disease detection, therapeutic targeting, and prevention strategies. Our goal is to translate fundamental discoveries into clinical applications that advance precision medicine for blood and immune-related disorders including cancer.