Single cell approaches for personalized medicine
In order to make the highly innovative single-cell technologies clinically usable for effective translation as quickly as possible, the Berlin Institute of Health is establishing a jointly supported, close interdisciplinary cooperation, in which BIH and Charité – Universitätsmedizin Berlin contribute clinical expertise (bioinformatics, imaging, machine learning, oncology, neurology, dermatology, biobanks, diagnostics and biomarkers) and the Max-Delbrück-Centrum/BIMSB technological and scientific expertise in the field of single-cell biology and gene regulation.
Single cell technologies for personalized medicine are a research focus of the BIH, the Charité and the Max Delbrück Center (MDC). Nikolaus Rajewsky (MDC) coordinates the focus area together with Angelika Eggert (Charité). The single cell analysis is also the basis for the pan-European LifeTime consortium: "Life Time: Revolutionizing Healthcare by Tracking and Understanding Human Cells during Disease".
The implementation is based on two pillars:
The establishment of three bridge junior research groups from BIH, MDC/BIMSB and Charité, which bring single cell expertise into clinical application. These junior research groups are located in the BIMSB building, where they have access to the latest single cell technologies and are in close contact with leading international scientists*. At the same time, each of these groups is integrated into a clinic at the Charité where they identify clinically relevant topics, use and develop single cell approaches to address specific clinical issues and establish the technologies for clinical use. This bridge concept optimally combines the internationally leading position of the BIMSB in the development of single cell technologies with the clinical-translational potential of BIH/Charité.
The development of a "Clinical Single Cell Sequencing" pipeline, which includes a central bioportal (patient sample collection, characterization and processing) as well as an integrated workflow with relevant genomics and bioinformatics services for the participating clinics.
Systems Hematology, Stem Cells & Precision Medicine
Cancer frequently originates from healthy stem and precursor cells that are responsible for the continuous regeneration of tissues and organs. A stepwise acquisition of genetic and molecular abnormalities transforms healthy stem and precursor cells into potentially malignant cancer cells. While this process occurs frequently, a complex interplay between the immune system, cancer cells, and factors from the microenvironment determine whether the newly emerging cancer cells are rapidly cleared or manage to establish a fully malignant cancer. The Haas group develops and applies novel multimodal single-cell and spatially-resolved technologies to study the complex etiology of hematological cancers and their interaction with the immune system. Another key objective of the research group is the development of next-generation precision diagnostic and prognostic technologies, based on high-content single-cell multi-omics technologies. These newly developed technologies aim at enabling early disease detection, highly precise, personalized treatment decisions and, ultimately, therapeutic intervention before disease onset.
Information will follow.
Stem Cell Dynamics & Mitochondrial Genomics
Hematopoiesis describes the process of blood formation and is sustained by the activity of hematopoietic stem and progenitor cells throughout our lifetime. While our understanding of stem cell biology continues to grow, it still remains challenging to study the in vivo activity of individual stem cells in humans. To overcome this, we develop single cell multi-omic approaches, in particular to detect naturally occurring sequence variation in the mitochondrial genome of our cells. Notably, a large fraction of hematopoietic cells develops unique mutational profiles, which we utilize as natural genetic barcodes to enable lineage tracing/assessments of clonal activity across the stem and progenitor cell pool. In conjunction with genomic readouts of cellular chromatin accessibility, gene and protein expression profiles, we aim to unravel fundamental principles of stem cell dynamics and (de-)regulation in disease states, including leukemia. Moreover, an interrelated key objective of the group is the study of how mitochondrial genotypes contribute to cellular phenotypes in congenital disorders, aging and common diseases.
Genome instability and somatic mosaicism
During normal development and ageing the cells in our body can acquire somatic mutations through diverse genome instability processes. These mutations are propagated and selected for over time. As consequence, we are actually a mosaic of unique somatic cell genomes, where any given cell in a tissue may be genetically distinct from another. Understanding how somatic mosaicism develops and evolves are central questions in the Sanders laboratory. With a focus on the genome, we develop and apply innovative single cell methods that explore the mechanisms of genome instability to understand how mutations arise and change cellular phenotypes in normal human tissues and disease states. By integrating multi-omic experimental and computational readouts, we ask how individual cells differ in terms of their unique genomic profiles, epigenetic programs and transcriptional outputs, and directly test the functional outcomes of somatic mutations to understand how they contribute to tissue homeostasis and human disease.
Prof. Nikolaus Rajewsky
Group Leader "Systems Biology of Gene Regulatory Elements", MDC
Prof. Angelika Eggert
Director Department of Paedriatrics, Department of Oncology and Hematology, Charité – Universitätsmedizin Berlin
Prof. Frank Heppner
Director Institute of Neuropathology, Charité – Universitätsmedizin Berlin
Prof. Norbert Hübner
Head of the lab "Genetics and Genomics of Cardiovascular Diseases", MDC
Dr. Jan Philipp Junker
Head of the lab "Quantitative Developmental Biology", MDC
Prof. Ulrich Keilholz
Director Charité Comprehensive Cancer Center (CCCC), Charité – Universitätsmedizin Berlin
Prof. Ana Pombo
Head of the lab "Epigenetic Regulation and Chromatin Architecture", MDC
Prof. Frank Tacke
Department Head, Department of Hepatology and Gastroenterology, Charité – Universitätsmedizin Berlin