Clinical Cooperation Unit Molecular Hematology/Oncology – Research Projects

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As a clinical cooperation unit, we are dedicated to knowledge transfer from basic research to clinical application. Hence, our research activities include basic, translational and clinical research projects.

Our basic research is focused on mechanisms of chromosomal instability, an important hallmark of cancer cells, with special attention to the regulation of mitosis and its disturbance in the context of oncogenesis, which may involve both the regulation of mitotic entry and the spindle checkpoint. Since centrosomal aberrations have been shown to lead to mitotic aberrations and chromosomal instability, a long-standing focus of our group is centrosome biology and its interconnection to cell cycle regulation and the DNA damage response. Recently published and ongoing projects therefore aim at the identification and characterization of novel – or incompletely characterized – centrosomal proteins playing important roles in centrosomal regulation of cell cycle transitions, the DNA damage response and neurodevelopmental disorders. Another focus of our research is the molecular dissection of pathways leading to centrosomal clustering, a mechanism by which cancer cells limit chromosomal instability by preventing multipolar mitoses in spite of supernumerary centrosomes being present.

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The latter mechanism is also an important focus of our translational research efforts, which aims at identifying centrosomal clustering inhibitors and introducing them as novel therapeutic agents.

Further efforts in cancer drug development are subject of a close collaboration with the Max-Eder-Junior Research Group “Experimental Therapies for Hematologic Malignancies”, which is headed by Marc-Steffen Raab and supported by the Deutsche Krebshilfe.

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A range of other projects focus on hematological malignancies as model diseases to gain new insights into pathophysiological mechanisms serving as a lead to novel therapeutic approaches. With support of the Deutsche Krebshilfe and in collaboration with Anna Jauch (Institute of Human Genetics, University of Heidelberg), mechanisms leading to and prognostic consequences of chromosomal instability are being investigated in neoplastic stem cells of myeloid origin (acute myeloid leukemias, myelodysplastic syndromes and myeloproliferative neoplasms), while a related project focuses on the prognostic impact of chromosomal aberrations in multiple myeloma. Further subjects of our research include nucleolar proteins and their role in hematological malignancies, and pathophysiological mechanisms involving tyrosine kinase fusion proteins in myeloproliferative neoplasms, a project which is supported by the Deutsche José Carreras Leukämie-Stiftung.

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Beyond laboratory research, several members of our department participate in clinical care as hematologists/oncologists – or trainees of this medical specialty – which takes place at the Department of Medicine V, University of Heidelberg. Here, we are involved in a range of clinical studies and are able to directly transfer latest research to the bedside.

Likewise, at the National Center for Tumor Diseases (NCT), we are responsible for the outpatient unit specialized on patients with carcinoma of unknown primary (CUP). Within this setting, we head a large national multi-center clinical trial investigating the addition of cetuximab to the standard treatment of carboplatin/paclitaxel in patients with CUP.

Max-Eder-Junior Research Group “Experimental Therapies for Hematologic Malignancies”

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