Date:
Wed, 18/01/202310:00-11:30
Location:
Danciger B building – Seminars Room
Lecturer: Efrat Shema Weizmann Institute
Abstract:
Genes and genomic elements are packaged by chromatin structures that regulate their activity. We developed a novel high-throughput single-molecule imaging technology to decode combinatorial modifications on millions of individual nucleosomes. We apply this technology to image nucleosomes and delineate their combinatorial epigenetic patterns, and how these patterns are deregulated in cancer. In addition, we adapt single-cell technologies based on CyTOF to profile the global levels of multiple histone modifications in single cells, thus revealing epigenetic heterogeneity in cancer. Our research focuses on pediatric gliomas harboring lysine to methionine substitution of residue 27 on histone H3 (K27M), as well as lymphoma and breast cancer. Our work establishes new concepts for the analysis of epigenetic interactions and heterogeneity in cancer that could be applied to diverse biological systems.
In addition, we harness the single-molecule technology as a novel liquid biopsy approach for cancer diagnostics. Our technology, coined EPINUC, enables multi-parametric comprehensive profiling of the Epigenetics of Plasma Isolated Nucleosomes, DNA methylation and cancer-specific protein biomarkers. Applying this analysis to a cohort of plasma samples detected colorectal cancer at high accuracy and sensitivity, even at early stages. Combining EPINUC with direct single-molecule DNA sequencing revealed the tissue-of-origin of the tumor. EPINUC provides multi-layered clinical-relevant information from limited liquid biopsy material, establishing a transformative approach for cancer diagnostics.
Abstract:
Genes and genomic elements are packaged by chromatin structures that regulate their activity. We developed a novel high-throughput single-molecule imaging technology to decode combinatorial modifications on millions of individual nucleosomes. We apply this technology to image nucleosomes and delineate their combinatorial epigenetic patterns, and how these patterns are deregulated in cancer. In addition, we adapt single-cell technologies based on CyTOF to profile the global levels of multiple histone modifications in single cells, thus revealing epigenetic heterogeneity in cancer. Our research focuses on pediatric gliomas harboring lysine to methionine substitution of residue 27 on histone H3 (K27M), as well as lymphoma and breast cancer. Our work establishes new concepts for the analysis of epigenetic interactions and heterogeneity in cancer that could be applied to diverse biological systems.
In addition, we harness the single-molecule technology as a novel liquid biopsy approach for cancer diagnostics. Our technology, coined EPINUC, enables multi-parametric comprehensive profiling of the Epigenetics of Plasma Isolated Nucleosomes, DNA methylation and cancer-specific protein biomarkers. Applying this analysis to a cohort of plasma samples detected colorectal cancer at high accuracy and sensitivity, even at early stages. Combining EPINUC with direct single-molecule DNA sequencing revealed the tissue-of-origin of the tumor. EPINUC provides multi-layered clinical-relevant information from limited liquid biopsy material, establishing a transformative approach for cancer diagnostics.