Contributio of a novel developmentally-restricted hematopoietic stem cell

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PROJECT SUMMARY/ABSTRACT The concept of a layered immune system entails the generation of specific functional components of the immune system at different stages of development. Despite three decades of research, the cellular mechanisms underlying immune layering have remained elusive. Our lab recently identified the cellular mechanism contributing to immune layering. Using a lineage tracing mouse model thoroughly characterized in our laboratory, we discovered a developmentally limited hematopoietic stem (HSC) that gives rise to developmentally restricted innate-like immune cells. These innate-like immune cells are critical mediators of immune tolerance and autoimmunity. Building on this discovery, my research interests focus on determining the developmental mechanisms underlying the establishment of immune tolerance and autoimmune susceptibility. I aim to define the unique function of this novel hematopoietic stem cell population in establishing innate immunity during development. I then seek to define the specific phenotypic, functional, and genetic attribute of immune cells generated from a developmentally-restricted HSC. Lastly, I aim to determine the effect of perinatal immune insult on developmental hematopoiesis, immune development and autoimmune disease susceptibility. This work will be conducted in the Institute for the Biology of Stem Cells at UC Santa Cruz in the lab of Dr. Camilla Forsberg, an expert in hematopoietic stem cell biology. Over the course of my doctoral training in nutritional sciences and my postdoctoral training in hematopoietic stem cell biology, I have gained considerable technical and intellectual breadth in developmental, molecular, and cell biology. My immediate goal is to broaden my training within immunology, including coursework, collaboration with expert immunology labs at UC San Francisco, and guidance by my co-mentor, Dr. Robert Coffman, a renowned expert in innate immunology. My long-term goal is to establish an innovative, independent research program at the interface of development, hematopoiesis and immunology.