Rejuvenating Aged Hematopoietic Stem Cells Through Multimodal Single-Cell Approaches
This project investigates how the pro-aging protein complex mTORC1 contributes to the functional decline of hematopoietic stem cells (HSCs), which sustain lifelong blood and immune cell production. While mTORC1 becomes overactive with age, broad inhibition has shown limited success due to off-target effects. The labs will use TerminaTOR, a genetically encoded mTORC1 inhibitor targeted to specific subcellular compartments such as the nucleus, lysosome, or cytoplasm, to dissect how location-specific mTORC1 activity drives aging-related changes in HSCs. Through single-cell multi-omic and metabolomic analyses in young and aged HSCs, the project will identify compartment-specific molecular signatures and test whether selective inhibition can rejuvenate stem cell function. These insights aim to inform safer, more precise interventions to combat age-related blood and immune system decline.
