We employ CRISPR-based genome editing methods combined with single-cell epigenomics to understand the molecular mechanisms of metabolic reprogramming in cancer. Read more about our research below!
The effect of metabolic reprogramming on cancer epigenome

To fuel their continuous growth, cancer cells exploit various cellular functions such as metabolic pathways. Understanding these processes at a single-cell level is crucial due to tumor heterogeneity, diverse responses to existing treatments, and the need for developing innovative treatment strategies for personalized medicine. 

Metabolic reprogramming provides building blocks for cellular components that are critical for proliferating cancer cells, but it can also directly modify the epigenetic state of chromatin. Our goal is to identify the metabolic enzymes and gene regulatory events that promote cancer cell proliferation through epigenome reprogramming. For this, we are utilizing various cancer cell models, CRISPR-screens and precision genome editing, single-cell epigenome and gene expression analysis and other genomics methods.

Competitive precision genome editing method

Competitive precision editing (CGE) method for cell proliferation was developed by me during my post-doctoral work (see original publication in Nature Biotech). It is based on Cas9-mediated genome editing using two homology-directed repair (HDR) templates, one for mutating the genomic feature of interest and another that reconstitutes the original genomic sequence. A unique molecular identifier (UMI) introduced by both HDR templates enables 

1) lineage-tracing of the edited cells during the experiment and 

2) direct comparison of two kinds of edited cells (mutated vs. original sequence) by discarding wild-type cells from the analysis. 

This mitigates common confounding effects in Cas9-screens, such as off-target effects and DNA damage from editing process itself affecting the proliferation