Award for Outstanding Medical Research

The Georg Friedrich Götz Foundation annually honors two researchers from the University of Zurich who have made outstanding, internationally recognized achievements in the field of basic or clinical research. On the Day of Clinical Research at the University Hospital Zurich (USZ) on 22 May 2025, the prize was awarded to Jana Ellegast, assistant professor of translational oncology at UZH and senior attending physician in the Department of Medical Oncology and Hematology at USZ, and to Jiang-An Yin, senior scientist at the Institute of Neuropathology.

Despite advances in treatment, more than half of all patients with acute myeloid leukemia (AML) still cannot be cured. To date, patients with AML have not been able to benefit from conventional immunotherapy.

Jana Ellegast and her team proposed that leukemia cells – essentially misguided immune cells – utilize cell-intrinsic immune signaling pathways for survival. Therefore, targeting and disrupting these pathways could serve as a form of cell-intrinsic, self-directed immunotherapy.

Through genome-wide screenings, the team identified the immunomodulator interferon regulatory factor 2 binding protein 2 (IRF2BP2) as a critical AML dependency. They found that IRF2BP2 suppresses the IL-1β/TNFα signaling pathway. When IRF2BP2 is acutely lost or its gene is knocked out, an excessive inflammatory response is triggered in leukemia cells, ultimately leading to their death.

The study revealed an unknown vulnerability of AML cells, identified excessive cell-intrinsic inflammation as a mechanism to induce leukemia cell death, and demonstrated that IRF2BP2-mediated transcriptional repression is a survival strategy for these cells. These findings open new avenues for therapies that specifically target AML.

Unbiased genetic screening is a foundational technique that has been greatly advanced by CRISPR technology. Current CRISPR screens use pooled guide RNA libraries, which have limited applicability to selectable phenotypes. On the other hand, arrayed CRISPR libraries significantly expand the scope of CRISPR screens. However, generating these libraries is challenging, and they are not widely available.

Over the past few years, Dr. Jiang-An Yin has developed a liquid-phase, high-throughput plasmid cloning method and has created arrayed libraries for genome-wide ablation of human protein-coding genes (19,936 plasmids) and for their activation and epigenetic silencing (22,442 plasmids). Each plasmid encodes an array of four non-overlapping guide RNAs designed to accommodate most human DNA polymorphisms. Studies have demonstrated that these new libraries surpass existing resources in superiority and versatility across various systems, including induced pluripotent stem cells and organoids.

Focusing on neurodegenerative diseases and the challenges posed by the limited success of clinical trials targeting disease-associated genes or their products, this CRISPR tool paves a new path for research. Dr. Yin has identified numerous novel, potentially druggable genes that regulate the pathology of Parkinson’s and prion diseases.