Decoding the epigenome for cancer research and diagnostics
Abstract: Epigenetic regulation of gene expression- the mechanism responsible for establishing and maintaining cellular identities during development- is frequently deregulated in cancer. In a multidisciplinary collaboration, the Shema lab (biology) and Ron lab (physics) develop a rich arsenal of tools to profile the combinatorial epigenetic network. Our single-cell and single-molecule technologies aim to parse the function of this network and its heterogeneity in human cancer, and utilize it for cancer diagnosis. The single-molecule imaging technology can decode the combinatorial modification patterns of millions of individual nucleosomes, and reveal how these patterns are deregulated in cancer. The single-cell technology is based on an adaptation of CyTOF and allows profiling of a wide panel of epigenetic modifications in thousands of cells, thus revealing epigenetic heterogeneity in 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.
Speakers:
Prof. Efrat Shema is an assistant professor at the Weizmann Institute of Science. She conducted her postdoctoral research at Massachusetts General Hospital and Harvard Medical School, where she pioneered a novel technology to study the epigenome using single-molecule imaging. In her lab at the Weizmann Institute, Dr. Shema’s research passion is to understand human genome regulation by the development and application of novel single-molecule and single-cell technologies to visualize the epigenome. Her goal is to reveal basic mechanisms of epigenetic deregulation in cancer, identify epigenetic vulnerabilities of cancer cells, and pave the way to new therapeutic opportunities that would benefit patients. Since starting her lab at Weizmann, Dr. Shema secured several prestigious grants and awards, such as the European Research Council Grant (ERC) and the prestigious European Research Council Proof of concept grant (ERC-PoC-2020) for the development and commercialization of a novel liquid biopsy diagnostic technology, recently published by her lab in Nature Biotechnology. Dr. Shema authored numerus publications in prestigious journals, with over 3000 citations.
Prof. Guy Ron is a Professor of Physics at the Hebrew University of Jerusalem. Prof. Ron did his PhD work in nuclear physics at Tel Aviv University and his Postdoctoral training at the Lawrence Berkely National Lab. Prof. Ron works mostly in the field of nuclear physics and utilizes accelerator facilities around the world to perform high precision measurements searching for deviations from the standard model of particle physics, which would be a hallmark of new physics. In addition, Prof. Ron’s group works in the field of material science, utilizing nuclear physics technique to measure physical properties of material and chemical systems, and develop novel detector technologies, such as the world’s most precise current sensor. Finally, Prof Ron is an expert in machine learning and data analysis, and has, for the last several years, partnered with the Shema group at The Weizmann Institute of Science to develop novel analytical tools for epigenetic studies. Prof. Ron holds the Cooper chair of nuclear physics at the Hebrew University, is a member of the Israeli Academy of Science nuclear physics committee, a board member of the European Physics Society nuclear physics board, was the recipients of an ERC starting grant, and has held many other prestigious grants and awards.
