Our goal is to understand the mechanisms regulating the development of human systems (both embryonic and adult). In particular, we are interested in clarifying the roles of both protein coding genes as well as pathobiology (disease state or pathogen) known to be uniquely human – therefore, not analogously studied in model organisms. Drawing on both pluripotent stem cell biology, hematopoiesis, and immunology, combined with novel high-content single-cell analysis (CyTOF – Mass Cytometry) and imagining (MIBI-Multiplexed Ion Beam Imaging) we are creating templates of ‘normal’ human cellular behavior. Using these we can decipher the roles of protein regulators on cellular specification as well as the influence of human-specific pathobiology on system remodeling at the single cell level. This work will enable a better understanding of how disease corrupts this process. Ultimately, our objective will be to use such approaches to not only reveal how novel regulators function in the context of complex cellular systems, but also enable the mechanistic characterization of human pathobiology in primary human tissues. In doing so we will understand how changes in related physiological or pathological systems can be more readily recognized and controlled.
In addition to the lab’s work on human hematopoiesis and pluripotent stem cell specification we are seeking collaborative partnerships surrounding problems in human immunology as well as in regenerative medicine, including efforts to exploit next generation single-cell analysis and new computational methods to create systems level models of these processes so that they may be better understood and directed.