About the Lab
The expertise of our lab is in studying tumour heterogeneity from a phenotypic, genomic, and functional perspective by combining advanced clonal tracking systems such as expressed lentiviral-based cellular barcoding with single cell sequencing platforms to understand the relationship between phenotype, genotype and function of malignant tumour cells. We apply these methods in a robustly quantitative manner to study cancer stem cell biology on a clonal level and at single cell resolution.
We are interested in the molecular mechanisms which govern clonal fitness and long-term regenerative activity with the aim of identifying which malignant cell types within a tumour are ultimately responsible for disease progression. Furthermore, we are probing the mechanisms which allow these clones to resist treatment to identify genetic susceptibilities which can be used to overcome treatment resistance.
For our work, we use primary patient material or models derived from these materials, such as patient-derived tumour xenografts, or patient-derived tumour organoids, to study the disease as close as possible to that of the patient. We work closely with a strong network of collaborators both nationally and internationally.
Nguyen LV et al. Cell Reports 2025: We mapped clonal growth and transcriptional states across a large panel of breast cancer patient‑derived xenograft models. We found that rare propagating cancer clones drive tumour growth and can reproducibly regenerate the full transcriptional landscape of their originating tumours. These cellular clones follow model‑specific differentiation programs and exhibit striking transcriptional plasticity, particularly in triple-negative breast cancers. Distinct cell fractions display different fitness, signaling, and metabolic properties, linking clonal behavior to functional tumour heterogeneity.
Shin HJ et al. STAR Protocols 2025: We developed a practical and scalable protocol for tracking clonal behavior by combining lentiviral DNA barcoding with single‑cell RNA sequencing. This method enables permanent labeling of individual cells, allowing clonal growth and function to be directly linked to transcriptomic states, and provides a robust framework for studying clonal fitness, plasticity, and heterogeneity in cancer and other model systems, offering new insights into the molecular mechanisms that underlie clone‑specific behavior.
Kronheim S et al. bioRxiv 2026: Using high‑complexity single‑cell barcoding and single‑cell RNA sequencing, we tracked thousands of individual single-cell-derived clones across breast cancer xenograft models during chemotherapy treatment. We show that chemotherapy rapidly and profoundly reorganizes the cellular clonal landscape, particularly in treatment‑nonresponsive tumors, where previously rare, drug‑resistant clones expand. Distinct cellular states exhibit different chemotherapy sensitivities, with epithelial and mesenchymal states responding differently in triple‑negative breast cancer. In ER+/HER2− models, chemotherapy induces stress‑adaptive, slow‑cycling “persister‑like” programs marked by DUSP1 and KLF4, revealing mechanisms that enable tumour cells to survive treatment and drive resistance.
