Prof. Dr. Barbara T. Grünwald

Tumor Heterogeneity and Translational Systems Biology

West German Cancer Center, Universitätsklinikum Essen

Phone: 0201/86535

Email

Modern profiling techniques have undoubtedly shown that tumors are not just mere lumps of tumor cells but comprise a multitude of cell types that together establish malignant function. Pancreatic tumors exhibit a famously abundant tumor microenvironment (TME) that affects every aspect of malignant behavior, serving as a prime example for a heterogenous multicellular tumor ecosystem. Despite this complexity, our previous work shows that pancreatic tumor tissues acquire few, well-definable functional programs that execute distinct tumor relevant functions and are rooted in regional differentiations state transitions within the cancer-associated fibroblast (CAF) compartment. We have identified distinct transcriptional drivers of such regional CAF states and are now, within the unique context of this CRC, aiming to deeply define the corresponding cell state transitions, their specific triggers and, most importantly, their precise transcriptional regulatory mechanisms. To this end, we apply precise acute perturbation approaches to state-specific transcription factors in advanced human in vitro models, followed by identification of transcriptional (co-)regulator and their CAF-specific target genes. Furthermore, we develop screenable readouts of the underlying cell state transition in order to dissect the specific contributions of a variety of potential triggers the cells are exposed to in human PDAC tissues and potentially grasp how these converge onto such few, functionally relevant tissue states.