Understanding haematopoietic stem cell fate choices by comparing distinct cellular states

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Haematopoiesis is a complex, finely-tuned process that produces trillions of new blood cells daily. Adult haematopoietic stem cells (HSCs) are responsible for the lifelong maintenance of this system, making it essential to understand their biology. The balance between mature cell production and HSC maintenance is primarily controlled by cytokines binding to receptors on HSCs and activating downstream signaling pathways. The recent discovery that cytokine receptor activation is more complex and diverse than previously thought leads to significantly more flexibility and diversity in fate choice probabilities, potentially explaining how some cytokines (e.g., SCF, TPO) can simultaneously support HSC maintenance and drive mature blood cell production. This project focuses on the biological mechanism of cytokine: receptor interaction in HSCs, informing efforts to modulate blood cell production and to produce vast quantities of HSCs outside the body. This project is highly interdisciplinary, studying single molecules in single mouse and human HSCs and leveraging new technologies/approaches in quantitative and biophysical biology. It builds on recent interdisciplinary projects in the host labs which apply new technologies to address fundamental biological questions in HSC biology (Nature, 2018) and cytokine receptor signaling (Science, 2020).