Medo Group PD Dr. Matúš Medo

Mutations in the genome are often not random but follow distinct patterns. These patterns, termed mutational signatures, are footprints of biological processes or past exposures to specific carcinogens. Mutational signatures can help to elucidate tumor evolution and have prognostic and therapeutic implications. 

Mathematical estimation of signature activities is a high-dimensional statistical problem. Although many tools for signature analysis have been developed, a recent analysis showed that no tool performs best under all conditions. 

We propose to identify the best-performing tool for a given task, cancer type, and number of mutations. This will be achieved by extensive prior testing of the existing tools on synthetic data under different conditions. We further propose to design a new tool that will explicitly include mutations that are not well explained by any known signature. 

With the two proposed tools, we aim to optimally use costly sequencing data and produce informed decisions for patient treatments.

Pandey group  Prof. Dr. phil. Amit V. Pandey

Castration-resistant prostate cancer (CRPC) represents a lethal stage of the disease, primarily driven by the tumor's ability to overcome therapy through the synthesis of its own androgens. 

Our research has advanced beyond studying single enzymes to investigate their higher-order organization into what we term "metabolic supercomplexes" or "metabolons." 

Our central hypothesis is that key enzymes in androgen production, such as CYP17A1, AKR1C3, and STS, do not function in isolation. Instead, they form organized, multi-protein complexes at the interface of cellular compartments, like the endoplasmic reticulum and the cytosol. These supercomplexes act as hyper-efficient production lines, utilizing a mechanism called "substrate channeling" to rapidly convert precursors into potent androgens that fuel cancer growth. 

This model provides a powerful new explanation for the robust resistance observed against drugs like abiraterone. Our current work focuses on characterizing the structure and function of these supercomplexes. The ultimate goal is to develop innovative therapeutic strategies that not only inhibit key enzymes but also disrupt the crucial protein-protein interactions that hold these metabolic machines together, potentially using novel small molecules or advanced nanoparticle-based delivery systems.

Reyes group Prof. Dr. Mauricio Reyes

In this project we aim to test the hypothesis that AI-based auto-segmentation technologies can be used for an AI-assisted multi-criteria quality assurance assessment in radiation therapy. The proposed multicriteria evaluation model is expected to provide a more objective review than traditional approaches, while at the same time focussing on clinically relevant radiotherapy aspects. The proposed Automated QUality Assurance in RadioTherapy (AQUA-RT) framework has the potential to increase consistency, improve delineation quality and reduce workload for routinely challenging quality assurance procedures.