Research in the Division Molecular Genome Analysis

The central objective of the Division of Molecular Genome Analysis is to reach an understanding of molecular mechanisms that regulate cellular communication and how these impact on cancer development and disease progression. Along these lines, we combine large-scale (sequencing, proteomics, data mining) and cell biology approaches to uncover the underlying processes and to eventually propose novel strategies for therapeutic intervention.
There, we focus on mostly three research areas, the investigation of functional signaling networks controlling drug effects, the discovery of coding and non-coding genomic driver alterations, and the quantification of pathway activities as potential contribution to informed clinical decision making.

Altered autocrine and paracrine signaling controls drug effects
Intra- and inter tumor heterogeneity are key factors affecting drug efficacy in individual patients. Mechanisms helping tumor cells persist drug treatment require immediate adaptation while long-term drug exposure establishes and fixes resistance states. We research on both, short-time drug effects and on long time resistance development, and there uncover molecular mechanisms underlying tumor cell survival. Along these lines, we investigate the impact cancer associated fibroblasts have on the failure of neoadjuvant chemotherapy in triple-negative breast cancer (e.g., Maia et al. 2021 Mol Onc, 15:1308-29). Further, we uncover mechanisms of endocrine therapy resistance in luminal breast cancer, the modulation of EGFR signaling in the context of diverse tumor entities, and the role and regulation of miRNAs and isomiRs also in a pan-cancer approach (e.g., Li et al, 2022, J Exp Clin Cancer Res, 41(1):190). -> Functional Networks

Coding and non-coding genomic drivers
Molecular alterations in cancer genomes are initial drivers of disease. We uncover driver alterations and functionally verify their driver potential mostly in rare tumor entities (e.g., Haller et al. 2019 Nature Communications 10:368). On top of aberrations within protein-coding genes, we characterize also mutations in regulatory sequences (structural variation, single nucleotide variants). Our research primarily aims at identifying causal events that may be exploited as diagnostic/prognostic markers or as drug targets.  -> Genome Analysis

Pathway activities for informed decision making
Disturbed wiring of pathways and networks is translated into phenotypes via proteins and protein activities. While the examination of mutations and their effects on gene expression has been a success in molecular tumor boards, we aim at establishing proteome and phosphoproteome analysis as complementary approach for informed decision making on therapeutic interventions (e.g., Wahjudi et al. 2021 Int J Cancer, 148(6):1438-51). More recently, we have moved into mass spectrometry-based analysis of tumor proteomes. -> Clinical Proteomics

Tools & Technologies
Molecular cancer research is driven also by advancements in technologies and tools. We have established reverse phase protein microarrays (RPPA) as a reliable and cost-effective experimental platform for quantitative protein profiling, and apply this in the tumor topics of the division and in collaborations. Furthermore, the division has been a driving force in national and international projects aimed at generating and providing tools to the scientific community. -> Tools & Technologies