Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer (Science Advances, 2021)
Here, we describe Copy-scAT, an R package that uses single-cell epigenomic data to infer copy number variants (CNVs) that define cancer cells.
High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma (Genome research, 2019)
We investigated the role of 3D genome architecture in glioblastoma stem cells (GSCs) by generating sub-5-kb resolution in situ Hi-C contact maps. Integration of DNA contact maps with chromatin and transcriptional profiles identified specific mechanisms of gene regulation, including the convergence of multiple super enhancers to individual stemness genes within individual cells.
Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma (Cancer Research, 2019)
Our analyses showed that all pediatric glioblastoma samples, including both diagnostic and recurrent samples, were collections of genetically diverse subclones. Analysis of variant allele frequencies supported a model of tumor growth involving slow-cycling cancer stem cells that give rise to fast-proliferating, progenitor-like cells and non-dividing cells. These findings support an important role for slow-cycling stem cell populations in contributing to recurrences, because slow-cycling cell populations are expected to be less prone to genotoxic stress induced by treatment and therefore would accumulate few mutations.
Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche (Development, 2016)
We identified two proteins, Six4 and Groucho (Gro), that link the activity of the EGFR and Notch signaling pathways to regulate the earliest cell fate decision in the FSC lineage. The phosphorylated form of Gro persists in newly formed prefollicle cells, which may delay differentiation and provide these cells with a temporary memory of the EGFR signal present in the FSC niche.