Research of the Grosswendt Lab

Multicellular life depends on cells communicating with their neighbors. These physical and biochemical interactions shape gene expression, cellular decisions and ultimately tissue function. Our lab aims to decode the language of cells by addressing four central questions: 

1. Which cells are neighbors?                       – mapping cell microenvironments –
2. How do they communicate?                      – deciphering ligand-receptor codes –
3. What are the consequences?                    – revealing gene regulation and fate decisions –
4. Can we make use of cell interactions?    – mimicking or disrupting communication – 

To tackle these challenges, our team of wet lab and computational biologists develop new single-cell-based genomic strategies to investigate how cells interact. Recently, we developed CellMate-seq (in revision, patent pending), a transcriptomics method that uncovers ligand-receptor dialogues between individual cells. Combined with spatial transcriptomics, we aim to identify the communication patterns that instruct the neural crest lineage of the developing mouse embryo. Neural crest cells pose an attractive system: they migrate through diverse microenvironments and are initially multipotent, giving rise to a variety of cell types whose specification is impacted by the signals they receive. By investigating cell interactions in neuroblastoma, we extend our research to a pediatric cancer derived from the neural crest lineage.

Decoding a language of cells means not only identifying the ‘syntax’ but also linking signals to their consequences. This is challenging because (i) the same signal can induce the expression of distinct genes in different cell types, and (ii) communication in tissues is rarely a two-body event – each cell interacts with multiple neighbors. To disentangle these complexities, we develop strategies in complex in vitro systems and pursue bottom-up reconstruction of cell interactions. With this we aim to uncover how diverse cell interactions collectively orchestrate the behavior and specification of cells in multicellular contexts.