Investigates human immunological diseases and malignancy through the development and leveraging of novel humanized mouse models
Complex biological processes often require in vivo analysis. A fundamental understanding of many biological processes in humans has stemmed from experimental studies in animal models, particularly in laboratory mice. For several decades, our lab has studied the molecular and cellular basis for pathological changes caused by spontaneous mutations that disrupt the development or regulation of the murine hematopoietic and immune systems. This knowledge has increased our understanding of human disease. Certain mutations result in severe combined immunodeficiency disease (SCID). We have applied the knowledge gained in our studies of SCID mice to optimize them to serve as hosts for human normal and malignant cells and tissues. There is a growing need for animal models to carry out research studies without putting human individuals at risk. We have developed SCID mouse models that support high levels of engraftment with human cells and tissues to overcome these limitations. We have collaborated nationally and internationally with colleagues to develop improved humanized mouse models and optimize the technologies used for engraftment of normal and malignant human cells and tissues. Our research has leveraged these models for translational studies on human hematopoiesis, immunity, autoimmunity, infectious diseases, diabetes, regenerative medicine and cancer.
Verma MK, Clemens J, Burzenski L, Sampson SB, Brehm MA, Greiner DL, Shultz LD. A novel hemolytic complement-sufficient NSG mouse model supports studies of complement-mediated antitumor activity in vivo. J Immunol Methods. [Epub ahead of print].
Walsh NC, Kenney LL, Jangalwe S, Aryee KE, Greiner DL, Brehm MA, Shultz LD. Humanized Mouse Models of Clinical Disease. Annu Rev Pathol. 12:187-215, 2017.
Boudreau JE, Liu XR, Zhao Z, Zhang A, Shultz LD, Greiner DL, Dupont B, Hsu KC. Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I. Immunity. 45(2):280-91, 2016.
Hosur V, Johnson KR, Burzenski LM, Stearns TM, Maser RS, Shultz LD. Rhbdf2 mutations increase its protein stability and drive EGFR hyperactivation through enhanced secretion of amphiregulin. Proc Natl Acad Sci U S A. 111(21):E2200-9. 2014.
Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 12(11):786-98, 2012.
Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa M, Doi T, Sone A, Suzuki N, Fujiwara H, Yasukawa M, Ishikawa F. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r ɣnull humanized mice. Proc Natl Acad Sci U S A. 107(29):13022-7, 2010.
Co-engrafting mice with human tumors that retain the same characteristics and human immune cells, is a new platform to study the...
Last week, leaders from multinational pharmaceutical and biotechnology companies, major academic cancer centers, health insurance...