Investigates human immunological diseases and malignancy through the development and leveraging of novel humanized mouse models
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Investigates human immunological diseases and malignancy through the development and leveraging of novel humanized mouse models
Our research leverages immunodeficient mouse models for translational studies on human hematopoiesis, immunity, autoimmunity, infectious diseases, diabetes, regenerative medicine and cancer. We have developed the NOD/SCID mouse strain harboring a null mutation of the IL2 receptor common gamma chain and have shown that these mice, referred to as NOD/SCID/Gamma (NSG) mice, efficiently support development of functional lymphoid and myeloid cells following human hematopoietic stem cell (HSC) engraftment. NSG mice have also been validated as an excellent host for engraftment with human T cells, myeloid cells, and other human cell populations.
Development of NSG mice that are humanized by engraftment with human tissues, stem cells and peripheral blood mononuclear cells (PBMCs) has provided an opportunity to study human biological processes in vivo that would otherwise not be possible. Our use of these mice in collaborative studies focused on infectious disease including HIV/AIDS has increased the understanding of human host responses to infection and has resulted in the discovery of new potential therapeutics for HIV. Our next generation of humanized mice express human cytokine and HLA transgenes as well as other human species-specific molecules and have targeted mutations that eliminate mouse MHC expression and further depress mouse innate immunity. Next-generation NSG mice are also being designed to support the growth of primary human hematopoietic as well as solid tumors that may have limited growth in currently available models. These mice are also becoming critical tools for the testing and validation of human cancer immunotherapy.