Group Harriet Wikman

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Identification and functional characterization of metastasis-associated genes in breast and lung cancer

The main research interest of our group is to understand the biology behind the different steps of the metastatic cascade. We are in particular interested in understanding and characterizing the mechanisms that enable early tumor cell dissemination, and to identify genes and pathways important for site specific metastasis in epithelial tumors. Our research focuses mainly on the three main tumor entities, i.e. breast, lung and prostate cancer.

By combining different whole genome screening methods we have identified genes and pathways important for both early lung and breast cancer tumor dissemination (Wrage et al., Clin Cancer Res 2009 and Int J Cancer 2015; Werner, Cancer Discovery 2015). We are currently performing functional characterization of different proteins, such as RAI2 and HERC5 important especially for the brain and bone metastasis formation (Werner et al., BMC Cancer. 2015; Hohensee et al., Oncotarget 2016). Furthermore, many of our projects focus on characterization and clinical relevance of circulating tumor cells (CTCs) identified in the blood of cancer patients (Hanssen et al., Scientific reports 2016).

We are using both patient derived material as well as cell-culture based model systems. In our research we therefore use a combination of many different genetic, biochemical and cellular analyses as well as functional genomics approaches (such as shRNA-mediated gene silencing) to understand the processes driving metastasis.

We are a group consisting of biologists and biochemists (master and PhD students and post docs), medical PhD students and a technician.

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Group of Simon Joosse

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Liquid biopsy guided therapy

The laboratory of Dr. Joosse focuses on using tumor markers in the blood of patients with breast and gynecological cancer to improve diagnostics, prognostics, and the prediction of therapy response.

We are investigating circulating tumor cells (CTCs) and cell-free, circulating tumor DNA (ctDNA) extracted from the blood for aberrations using advanced techniques such as Third and Next Generation Sequencing (long read sequencing). By identifying and characterizing these so called Circulating Tumor Cells (CTCs) we might be able to determine the metastatic potential of these cells, which might ultimately lead to improved treatment options for cancer patients.

We are a group consisting of 10-13 medical scientists, clincal scientists, PhD students, technicians, medical students, and MSc BSc students.

If you are interested in an internship or performing your PhD or MD in our laboratory, please feel free to send me your English CV and motivation letter by e-mail.

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Group Katharina Harms-Effenberger

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CTC/DTC detection and characterisation: pancreatic and esophagus carcinoma

In cooperation with the Department of General, Visceral and Thoracic Surgery at UKE our working group is focussed on disseminated tumor cells in bone marrow (DTC) as well as circulating tumor cells in peripheral blood (CTC) of patients with pancreatic, esophageal and lung cancer. DTC and also CTC are of prognostic relevance in many solid tumor entities, as for example breast cancer, and serve as prognostic markers for early metastatic relapse and reduced survival in these patients.

Our goal is the improvement of appropriate DTC and CTC detection platforms for the above mentioned tumor types. Based on immunomagnetic and immunocytochemical methods different enrichment protocols as well as detection systems are compared. Once DTC/CTC are detected molecular single cell characterisation shall identify potential therapeutic targets to finally antagonize metastatic disease progression.

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Hypoxic stress reaction in breast cancer cellseiter

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Cell stress and dissemination

Tumor cells are frequently exposed to adverse microenvironmental conditions or to rapid changes of their microenvironment. Adverse conditions may be low oxygen partial pressure (hypoxia) or low glucose levels (hypoglycemia), while rapid changes in the microenvironment may occur when primary tumor cells disseminate to novel microenvironments at secondary organs. In both circumstances stress in the tumor cells is induced, leading to activation of special cytoprotective programs to maintain cellular functions.

In focus of our research is the settlement of disseminated breast tumor cells into the bone marrow microenvironment. This process is characterized by rapid changes of microenvironment of the tumor cells in the course of the dissemination from the primary tumor into the blood circuit and settlement in bone marrow. In addition, the hematopoietic stem cell niche of the bone marrow exhibits a low oxygen partial pressure, which may induce cell stress in tumor cells that are disseminated to this site.

Since adaptation to cell stress is a response to unphysiological conditions, it rarely occurs in normal cells. Hence, proteins of cytoprotective programs like the unfolded protein response are suitable marker proteins for the detection of tumor cells. Moreover, increased tolerance of the tumor cells against microenvironmental stress can confer tolerance against therapeutic approaches as well. In turn, identification of vulnerabilities in stress response programs may reveal structures that allow a specific targeting of those cells. Consequently, discoveries in the tumor cell stress responses can provide tools that allow the specific detection and the targeting of exceptionally resistant tumor cells.

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