LSRII flow cell lasers: photo by David Parks

LSRII flow cell lasers: photo by David Parks

what we do

We study the development and function of the mammalian immune system at a single-cell level. Our goal is to understand the differences between the immune cells that develop preferentially in infants versus adults, and determine the functional impact of these differences in promoting host immunity or immunopathology.

Our studies combine high-dimensional flow cytometry and multi-OMICs single-cell sequencing technologies as a Systems Immunology approach to study the development and function of tissue-resident immune cells, including tissue-resident macrophages and B lymphocytes that develop early during embryogenesis and persist in tissues throughout adulthood. We use in vivo mouse models of lineage-tracing and fate-mapping, humanized mice, and patient/clinical samples to study the differences between tissue-resident versus circulating immune cells.

 

High-dimensional single-cell technologies: flow cytometry/cell sorting and single-cell sequencing (V(D)J B and T cell receptor repertoire; protein expression (Ab-seq), 3’- and 5’-total gene expression)

 

what we want

We expect our studies, from both basic and translational research, to provide new insights into the development and function of the human immune system in infants and adults and shed light on the mechanisms that lead to organ-specific inflammatory disorders (including infectious diseases, autoimmunity, cancers, and immunodeficiencies) that predominant at different developmental ages, and inform the development of new vaccines that are targeted to either children or adults.

of mice and men

 

differences between the fetal, neonatal, and adult immune system

 
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The mammalian immune system develops progressively during ontogeny. In both mice and humans, the types of immune cells that develop in infants differ from those that develop in adulthood. Our goal is to understand the differences between the immune cells that develop preferentially in fetal, neonatal, and adult life, and determine the functional impact of these differences in promoting host immunity or immunopathology.

Recently, we have identified, in mouse models, lineages of innate-like tissue-resident B lymphocytes and macrophages that develop in the fetus (but not adults) independently of the long-term hematopoietic stem cells (LT-HSC). We are also using humanized mice to investigate the development and function of these innate-like tissue-resident B lymphocytes and macrophages in humans, during both infancy and adulthood.

 

current projects