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.
This project examines the cellular mechanisms underlying developmental hematopoietic waves and immune cell layering, and the effect of perinatal insult on immune disease susceptibility. Understanding determinants of early susceptibility to immune disease is critical for identifying targets for prevention, as well as identifying populations at risk in order to guide early intervention efforts.
|Valentine, Kristen M; Davini, Dan; Lawrence, Travis J et al. (2018) CD8 Follicular T Cells Promote B Cell Antibody Class Switch in Autoimmune Disease. J Immunol 201:31-40|
|Apostol, April C; Beaudin, Anna E (2018) Reversing Time: Ezh1 Deficiency Hastens Definitive Hematopoiesis. Cell Stem Cell 22:285-287|
|Cole, Charles; Byrne, Ashley; Beaudin, Anna E et al. (2018) Tn5Prime, a Tn5 based 5' capture method for single cell RNA-seq. Nucleic Acids Res 46:e62|
|Byrne, Ashley; Beaudin, Anna E; Olsen, Hugh E et al. (2017) Nanopore long-read RNAseq reveals widespread transcriptional variation among the surface receptors of individual B cells. Nat Commun 8:16027|
|Beaudin, Anna E; Forsberg, E Camilla (2016) To B1a or not to B1a: do hematopoietic stem cells contribute to tissue-resident immune cells? Blood 128:2765-2769|
|Beaudin, Anna E; Boyer, Scott W; Perez-Cunningham, Jessica et al. (2016) A Transient Developmental Hematopoietic Stem Cell Gives Rise to Innate-like B and T Cells. Cell Stem Cell 19:768-783|