Understanding the physical biology of adult blood stem cells

The discovery of functional heterogeneity in normal and malignant stem cells has shifted our understanding of how single cells are subverted to drive cancer. To design therapies for diseases of stem cell origin and to better provide cell populations for clinical applications, it is critical to understand this diversity at the single cell level. This proposal focuses on understanding the complex biology of normal and malignant stem cells and the impact of individual mutations on clonal evolution by studying the physical and quantitative aspects of single blood stem cells. This proposal aims to study single blood stem cell biomechanics and clonal evolution by leveraging new inter-disciplinary technologies and approaches and applying them to functionally defined mouse and human blood stem cell populations. It will combine in vitro and in vivo biological assays with mathematical modelling and microfluidic technology in an iterative manner across both human and mouse stem cell populations.