CRISPR/Cas9-mediated genome editing for genetic transformation of the adrenal cortex and adrenocortical tumorigenesis
Department of Internal Medicine I, Division of Endocrinology and Diabetes
Dr. rer. nat.
Biocenter of the University of Würzburg
Chair of Biochemistry & Molecular Biology
Michaela Reissland – PhD
Oliver Hartmann – PhD
Nikolett Pahor – PhD
Viktoria Marnet – MD student
Angela Grün – TA
Advancements regarding novel treatment strategies for adrenocortical carcinoma as well as fostered understanding of potential drivers of adrenocortical tumorigenesis have been limited by the lack of tumor models reflecting genetic disease heterogeneity. To gather new insights into disease onset and identify new therapeutically relevant targets, it is obvious that new tools are desperately required to advance the field of ACC research. In this regard, we established a novel workflow for culturing and longitudinal propagation of non-transformed adrenocortical cells. This unique ex vivo setup holds the potential to study adrenal cell homeostasis and biology, and allows us to replicate oncogenic transformation of adrenocortical cells using CRISPR/Cas9-mediated genome editing. It furthermore presents a starting point for the development of versatile and clinically relevant isogenic mouse models for adrenocortical tumors and enables members of the consortium to validate putative translational findings in clinically relevant model systems, genetically tailored to suit the question.
(I) Establish primary adrenocortical cultures derived from different mouse strains, sexes and human adrenal glands
(II) Immortalization and cell-specific oncogenic transformation of generated cell lines using CRISPR/Cas9 reflecting common mutations identified in ACC
(III) Generation and characterization of corresponding mouse models
Publications (CRC/TRR 205 included)