Lisa Minter

My area of research focuses on the role NOTCH1 signaling plays in autoimmune responses. We are currently investigating how NOTCH signaling contributes to pathology and disease progression during immune-mediated bone marrow failure (BMF). We have established two new models of BMF, both of which are highly representative of the human immune-meditated BMF syndrome, Aplastic Anemia. In our first model, we transfer bulk splenocytes from a parental C57BL/6 strain into recipient mice that are the F1 hybrid progeny of a C57BL/6 x BALB/c cross. The result is a robust graft-versus-host response whereby the transferred splenocytes selectively target the bone marrow for destruction. The onset of disease is precipitous and symptoms include loss of repopulating stem cells from the bone marrow and immune cells from the periphery, infiltration of destructive CD4+ and CD8+ T cells into the recipient BM, as well as increased levels of the pro-inflammatory cytokines, interferonγ and TNF in the circulation. Our “humanized” model utilizes a recently developed transgenic mouse strain, Nod/SCID/IL2Rγcnull (NSG), in which BMF is induced following the transfer of human peripheral blood mononuclear cells.