Research

Single-Cell Epigenetic Analysis of Tumors

Cancer cells are highly heterogeneous, both at the transcriptional level and at their epigenetic state. While single cell RNA sequencing technologies have revolutionized our understanding of transcriptional heterogeneity, the plethora of histone post-translational modifications (PTMs) is still mainly analyzed using bulk methods. We adapted Cytometry by Time of Flight (CyTOF) to analyze a wide panel of histone modifications and chromatin regulators in various cancer models.

Novel Liquid Biopsy Systems for Cancer Diagnostics

The cell-free DNA (cfDNA) that circulates in the plasma and serum of humans mostly originates from apoptosis of normal hematopoietic cells. In some physiological conditions or diseases, cfDNA may originate from a different distribution of tissues, a phenomenon that is being exploited for clinical applications. We establish methodologies to identify the tissue contribution of plasma circulating nucleosomes under different physiological conditions that leverage the unique properties of the single-molecule chromatin profiling technology.

Epigenetic Drivers of B-cell Lymphomas

Diffuse-Large-B-Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma, an aggressive cancer with high metastasis rates. About 85% of tumors contain mutations in epigenetic modifiers, and often multiple hits are observed in one tumor. These mutations occur early in lymphogenesis and contribute to the maintenance of the highly proliferative germinal center program.

The Effect of Oncohistone Mutations on the Combinatorial Epigenome

Whole genome sequencing efforts highlighted recurrent cancer-associated mutations in the genes encoding the core histones comprising the nucleosome structure. High-grade pediatric gliomas often carry gain-of-function mutations in the H3 gene (‘oncohistones’), which result in extensive deregulation of the chromatin landscape. We apply our single-molecule imaging platform and advance chromatin profiling strategies to decipher chromatin incorporation and combinatorial epigenetic patterns associated with mutant nucleosomes.

Epigenetic and Metabolic Rewiring in IDH-mutant Gliomas

Epigenetic and metabolic aberrations are considered early events during gliomagenesis and often define specific glioma subtypes. Isocitrate dehydrogenase (IDH1/2) enzymes are frequently mutated in adult gliomas, and their mutation status is currently used for CNS tumor classification. We combine multiple methodologies to explore the tight interaction between chromatin regulation and metabolism in these tumors.

Epigenetic Heterogeneity and Plasticity in Breast Cancer

Breast cancer is a highly heterogeneous disease that can be caused by a variety of distinct genetic alterations in mammary epithelial cells, with five biologically and clinically distinct intrinsic breast cancer subtypes. Cellular plasticity may facilitate the conversion between subtypes within the same tumor and generate intra-tumor heterogeneity. Moreover, the distinct breast cancer subtypes specifically shape their microenvironment, determining cancer treatment and prognosis.

The Epigenetic Network in Embryonic Stem Cells

This project aims to understand how histone modifications on H3 lysine 27 affect the epigenetic network in stem cells (mESCs). By measuring dozens of epigenetic marks at the same time with cytometry by time-of-flight (CyTOF) we reveal changes in the epigenetic network and link them to early developmental stages.