Education and Training
Christoph Plass is head of the division Cancer Epigenomics at the German Cancer Research Center (DKFZ), Heidelberg (Germany), and full professor at Heidelberg University Medical Faculty. After his graduation in Biology from the Freie Universität Berlin (Germany), he conducted his postdoc at the Roswell Park Cancer Institute, Buffalo NY, USA. He habilitated in 2005 at der Ohio State University, Columbus, USA and has been working at DKFZ since 2007.
Expertise
Epigenomic Profiling and genomics of lung diseases.
Cancer Epigenomics
- Lung cancer (LC)
- Chronic Obstructive Pulmonary Disease (COPD)
Christoph Plass | Professor | ||
Maria Llamazares Prada | Senior Postdoc | ||
Mei-Ju Chen | Postdoc | ||
Kathleen Schlüter | Doctoral student | ||
Nan Zhang | Doctoral student |
Lung Research - Projects
- Many lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share the hallmark of airway mucus obstruction. Nevertheless, the role of excess mucus in the in vivo pathogenesis remains largely elusive. The team hypothesizes that muco-obstruction leads to epigenetic changes in airway macrophages (AM), driving pathogenesis through inflammation and emphysema. In order to detect epigenetic aberrations, they applied several genome-wide sequencing approaches to AM. Homogenous cell populations were isolated via fluorescence activated cell sorting (FACS – in collaboration with Michelle Paulsen, partner UKHD) from a mouse model overexpressing epithelial Na+ -channel (ßENaC), which share key characteristics of muco-obstructive lung diseases.
- The cancer initiating cell type in lung adenocarcinoma (LUAD) is suspected to be ATII cells, mostly based on that tumors express SPC, an ATII marker. In a collaboration with Rocio Sotillo (DKFZ), the team is using an inducible CreER lineage tracing system and low input whole genome bisulfite sequencing to elucidate the cell type of origin in lung adenocarcinoma. Beside ATII cells, Club cells showed the capability to give rise to cancer. Methylation patterns indicate that the Club cell originating tumors show high similarity to those with ATII cells of origin, suggesting trans-differentiation between cell types upon tumorigenesis.
The Human Lung Cell Methylome and Proteom Atlas: Neoplastic growth is initiated by genetic/epigenetic alterations occurring in the cell-of-origin. During subsequent evolution, the cancer genome acquires additional alterations, which accelerate the tumorigenic process. These (epi)genetic alterations are translated into unique gene expression profiles, that determine the malignant phenotype, including its aggressiveness and response to therapy and will guide clinicians in their therapeutic choices. For many cancers, the precise cell-of-origin is unknown leading to an inaccurate diagnosis and suboptimal treatment. This lack of precision is unacceptable, since the cell-of-origin is characterized by a unique epigenome, which in part predetermines the future phenotype of a malignancy. Identifying this cell by epigenetic profiling could provide us with such knowledge. The cell-specific epigenome is faithfully copied into the daughter cells during cell division. However, during cell differentiation, aging and in response to environmental stimuli the epigenome is subjected to modulation and reprogramming. Consequently, each cell-type and its associated developmental stages carry distinct and highly informative epigenetic patterns, which can be measured at the single-nucleotide level as DNA methylation or histone modification profiles using exquisitely sensitive next generation-based sequencing technologies and single-cell analysis. To determine the malignant phenotype of NSCLC, we will generate and compare epigenetic datasets of normal lung and NSCLC cell types.