Research of the Lindeboom lab

The Lindeboom lab uses quantitative biology to understand how cells maintain their identity and communicate with the immune system. We develop approaches to measure molecular copy numbers, binding rates and turnover rates across the proteome, transcriptome and epigenome. These measurements allow us to build models that explain how cancer cells change state and become recognised by immune cells.

Our work is organised around two connected themes: quantitative antigen recognition and quantitative transcription factor biology.

Quantitative antigen recognition

T cells recognise diseased cells through interactions between T cell receptors and antigens presented on the surface of cancer cells. Yet immune recognition is not determined by antigen identity alone. The same antigen-specific interaction can lead to activation, killing, dysfunction or escape depending on antigen abundance, synapse composition, receptor dynamics and T cell state.

We study antigen recognition as a quantitative biochemical process between cancer cells and T cells. We investigate how proteostasis shapes antigen abundance, including in rare cancers through the RADAR consortium, where we map proteome dynamics and antigen presentation using bulk and single-cell proteomics. We then ask how antigen abundance is interpreted at the immunological synapse, how synapse composition changes across APC types and T cell states such as exhaustion, and how receptor flux during T cell engagement reveals new activating and inhibitory pathways.

Finally, we connect molecular maps to function by testing candidate regulators in engineered antigen-presenting systems and T cell assays. Together, this work aims to explain when T cells ignore cancer cells, eliminate them or become dysfunctional.

Quantitative transcription factor biology

We also study how the abundance of regulatory proteins controls cell identity. Many oncogenes act as tightly regulated proto-oncogenes in healthy cells, but gain new regulatory activities in cancer when their expression is elevated, for example by genomic amplification.

We aim to understand how DNA-binding proteins activate different regulatory programmes at different expression levels. To do this, we developed BANC-seq, a method to measure how protein concentration affects binding across the epigenome. Using inducible breast cancer transformation models, we tune oncogenic transcription factor abundance and study how concentration-dependent binding, chromatin remodelling and gene regulation drive changes in cell fate.

Because transcription factor binding is shaped by both DNA sequence and chromatin state, we are developing approaches to resolve binding into kinetic parameters. This allows us to ask how genetic and epigenetic features tune binding dynamics, and how these principles differ between pioneering and non-pioneering transcription factors.

Together, our work aims to define how molecular abundance and dynamics control cancer cell identity and tumour-immune communication.