We are able to design experimental systems that assess specific gene functions or mechanisms of disease, both in vitro and in humanized animal models, due to the availability of disease-focused, viable cell inventories and associated deep clinical and molecular phenotyping data, through the ACI Biorepository. Leveraging the ability to reprogram human somatic cells into induced-pluripotent stem cells (iPSC), we are then able to generate many different types of cells through either in vitro or in humanized animals reconstituted with these stem cells and study those cells in a very controlled set of experiments. This further allows for specific somatic cell gene modifications to be introduced through techniques such as CRISPR/Cas9 directed mutations.
The Guthridge Lab is using these models in the project focused on dissecting the Ikaros (IKZF1) lupus associated gene risk allele functional effects on cellular differentiation and autoimmune associated responses.