Prof. Dr. Raffaella Santoro

Department of Molecular Mechanisms of Disease (DMMD), University of Zurich

DMMD - Research
Santoro Lab
Contact

Despite sharing the same genome, different cell types from a given organism respond differently to environmental, developmental or metabolic cues. This variable property is a defining aspect of a cell’s identity and is mainly interpreted at the level of epigenetic signature and chromatin organization. A complex epigenetic network, which includes the coordinated action of histone modifying enzymes, DNA methyltransferases and non-coding RNAs regulate cell functions throughout a person’s lifetime and establish the blueprint for the tissues of the developing embryo. Consequently, each cell has its own epigenetic pattern that must be carefully established and maintained to regulate proper gene expression. Perturbations in these carefully arranged patterns can lead to congenital disorders or predispose people to acquire disease states such as cancers. Primary goals over the next decade will include improving our understanding of the epigenetic mechanisms and gene expression in physiological and pathological conditions, and offer important strategies for the development of effective therapies and diagnosis markers for a wide variety of diseases, including cancer.

The aim of our laboratory is to understand epigenetic regulatory systems that contribute to the susceptibility and development of complex diseases. Our research is focused on the basic understanding of epigenetic regulation and translating the acquired knowledge to provide important information for personalized treatment and diagnosis. We address challenging questions of epigenetic regulation in physiological and pathological conditions such as:

1. How chromatin and epigenetic states are inherited during cell division

2. How chromatin and epigenetic states are implicated in the pluripotency of embryonic stem cells

3. How epigenetic alterations in cancer genomes are established and their role in disease progression and clinical outcomes

Our expertise comprise the following:

• Chromatin analysis: Chromatin immunoprecipitation (ChIP-seq); Chromatin fractionation; Histone modifications.
• DNA methylation analysis: Bisulphite; Enzymatic measurements (meC and hmeC); MeDIP and hMeDIP; Methylation-ChIP assay (ChIP-chop).
• Gene transcription and non-coding RNA: qRT-PCR, RNA-seq.
• Establishment of inducible cell lines expressing shRNAs and tag-proteins.
• CRISP-Cas9 genome editing.
• Immunofluorescence of nucleolar, nuclear and histone proteins.
• Purification of protein complexes.