Cell & Animal Lab
Our research group focuses specifically on biomarkers (imaging, tissue and liquid biopsies) of malignant disease. Especially in the setting of oligometastases a better understanding of disease activity, extent and spread is required to tailor personalized treatment approaches.
Integrated Diagnostics is a new frontline within the multidisciplinary treatment of diseases, where multiple pillars of diagnosis such as imaging, liquid biopsy, molecular pathology and clinical data science are converging. Imaging by itself frequently is not able to provide sufficient information, neither on characterization of a certain disease, nor on the response to treatment. Therefore, additional biomarkers are required to gain a comprehensive picture of a certain pathophysiology and state of disease. As such, biomarkers retrieved from tissue and liquid biopsies complement data from non-invasive biomedical imaging.
Our research group focuses specifically on biomarkers (imaging, tissue and liquid biopsies) of malignant disease. Especially in the setting of oligometastases a better understanding of disease activity, extent and spread is required to tailor personalized treatment approaches. For example, the assessment of minimal residual disease (MRD), defined as a malignant lesion not detectable by existing diagnostic modalities but nevertheless posing the patient to a high risk of recurrence specifically requires a multimodal assessment of the malignant disease. In this context, our laboratory aims to understand the molecular and cellular ground of malignant disease, characterizing the triggering pathways and unraveling new predictive markers.
For assessing disease status and activity we investigate components of the tumor microenvironment after local ablative tumor therapies applying dedicated tissue biopsy regimens during the course of interventional oncologic treatments. We thereby try to understand signals involved in the early phase after local ablative therapies in the oligometastatic setting, exploring the role of immune cell infiltration and activation in peritumoral tissue.
Complementary to tissue analysis, liquid biopsies help to understand altered post-treatment signaling pathways which may contribute either to local tumor progression or accelerate the response to therapy. Via soluble molecules obtained from peripheral blood predictive models can be generated to improve response monitoring. In our research we focus on the role of the identification and the characterization of circulating tumor cells (CTC) and tumor-derived circulating molecules, such as exosomes, circulating tumor DNA and microRNA, which not only trigger the metastatic disease but also support the identification of cancer lesions at a stage when standard imaging procedures are still failing.
While conventional imaging fails to assess the biological activity of a certain disease, molecular imaging depicts distinct aspects of disease activity, such as metabolism, immune activation and proliferation. While the various -omic approaches existing can address these aspects very specifically, they only provide a snapshot of the disease. Molecular imaging can trace these biomarkers over time, thereby providing information on the localization and expression levels of certain biomarkers dynamically. We apply optical, nuclear as well as molecular magnetic resonance techniques to address specific aspects of disease formation as well as therapy monitoring.
For a comprehensive integrated diagnostic approach, structured biobanking of tissue and blood samples is mandatory. For this purpose, we integrate biobanking in almost every clinical trial. Patients undergoing interventional oncology treatments undergo repetitive sampling of blood and tissue together with biomedical imaging according to dedicated schemes. This structured collection of imaging, tissue and blood biomarkers enables a comprehensive assessment of disease status in oncology. Grooming and integration of these multiple diagnostic markers finally adds up to the concept of integrated diagnostics.
Currently ongoing, together with the Department for Gastroenterology and Hepatology at KUM we are establishing HEP-KUM, a unique liver biobank with extensive collection of human bio-samples which will offer a valuable resource for the study of liver diseases from early cirrhosis to advanced liver disease including hepatocellular carcinoma.
Dr. hum. biol. Heidi Hirner-Eppeneder
National Cancer Centre Singapore
Prof. Pierce Chow
Hadassah Hebrew University Medical Center, Israel
Prof. S. Nahum Goldberg
Translational Research Imaging Center, Department for Radiology, Universitätsklinikum Münster
Prof. C. Faber
Institute for Analytical Chemistry, University of Münster, Germany
Prof. U. Karst
Gerwing M, Kocman V, Stölting M, Helfen A, Masthoff M, Roth J, Barczyk-Kahlert K, Greune L, Schmidt MA, Heindel W, Faber C, König S, Wildgruber M, Eisenblätter. Tracking of Tumor Cell-Derived Extracellular Vesicles In Vivo Reveals a Specific Distribution Pattern with Consecutive Biological Effects on Target Sites of Metastasis. M. Mol Imaging Biol. 2020 Jul 31.
Yang H, Jüstel D, Prakash J, Karlas A, Helfen A, Masthoff M, Wildgruber M, Ntziachristos V. Soft ultrasound priors in optoacoustic reconstruction: Improving clinical vascular imaging. Photoacoustics. 2020 Mar 10;19:100172.
Baehr A, Umansky KB, Bassat E, Jurisch V, Klett K, Bozoglu T, Hornaschewitz N, Solyanik O, Kain D, Ferraro B, Cohen-Rabi R, Krane M, Cyran C, Soehnlein O, Laugwitz KL, Hinkel R, Kupatt C, Tzahor E. Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs. Circulation. 2020 Sep;142(9):868-881.
Kimm MA, Shevtsov M, Werner C, Sievert W, Zhiyuan W, Schoppe O, Menze BH, Rummeny EJ, Proksa R, Bystrova O, Martynova M, Multhoff G, Stangl S. Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors. Cancers (Basel). 2020 May 22;12(5):1331.
Alunni-Fabbroni, M., K. Ronsch, T. Huber, C. C. Cyran, M. Seidensticker, J. Mayerle, M. Pech, B. Basu, C. Verslype, J. Benckert, P. Malfertheiner, and J. Ricke. Circulating DNA as prognostic biomarker in patients with advanced hepatocellular carcinoma: a translational exploratory study from the SORAMIC trial. J Transl Med 2019 17 (1):328.
Trapp, E., W. Janni, C. Schindlbeck, J. Juckstock, U. Andergassen, A. de Gregorio, M. Alunni-Fabbroni, M. Tzschaschel, A. Polasik, J. G. Koch, T. W. P. Friedl, P. A. Fasching, L. Haeberle, T. Fehm, A. Schneeweiss, M. W. Beckmann, K. Pantel, V. Mueller, B. Rack, C. Scholz, and Success Study Group. Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer During Follow-Up and Prognosis. J Natl Cancer Inst 2019 111 (4):380-387.
Masthoff M, Buchholz R, Beuker A, Wachsmuth L, Kraupner A, Albers F, Freppon F, Helfen A, Gerwing M, Höltke C, Hansen U, Rehkämper J, Vielhaber T, Heindel W, Eisenblätter M, Karst U, Wildgruber M, Faber C. Introducing Specificity to Iron Oxide Nanoparticle Imaging by Combining 57Fe-Based MRI and Mass Spectrometry. Nano Lett. 2019 Nov 13;19(11):7908-7917. doi: 10.1021/acs.nanolett.9b03016. Epub 2019 Oct 2. PMID: 31556617
Nowacki TM, Lenz P, Bettenworth D, Brückner M, Bokemeyer A, Tepasse PR, Helfen A, Wildgruber M, Eisenblätter M. Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis. Cells. 2019 Oct 28;8(11):1328. doi:10.3390/cells8111328. PMID: 31661876.
Gerwing M, Herrmann K, Helfen A, Schliemann C, Berdel WE, Eisenblätter M, Wildgruber M. The beginning of the end for conventional RECIST - novel therapies require novel imaging approaches. Nat Rev Clin Oncol. 2019 Jul;16(7):442-458. doi: 10.1038/s41571-019-0169-5. PMID: 30718844
Alunni-Fabbroni, M., L. Majunke, E. K. Trapp, M. Tzschaschel, S. Mahner, P. A. Fasching, T. Fehm, A. Schneeweiss, T. Beck, R. Lorenz, T. W. P. Friedl, W. Janni, B. Rack, and Success Study Group. Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients. BMC Cancer 2018 18 (1):141.2018.
de Wit, S., M. Manicone, E. Rossi, R. Lampignano, L. Yang, B. Zill, A. Rengel-Puertas, M. Ouhlen, M. Crespo, A. M. S. Berghuis, K. C. Andree, R. Vidotto, E. K. Trapp, M. Tzschaschel, E. Colomba, G. Fowler, P. Flohr, P. Rescigno, M. S. Fontes, R. Zamarchi, T. Fehm, H. Neubauer, B. Rack, M. Alunni-Fabbroni, F. Farace, J. De Bono, I. Jzerman MJ, and Lwmm Terstappen. EpCAM(high) and EpCAM(low) circulating tumor cells in metastatic prostate and breast cancer patients. Oncotarget 2018 9 (86):35705-35716.
Busse M, Müller M, Kimm MA, Ferstl S, Allner S, Achterhold K, Herzen J, Pfeiffer F. Three-dimensional virtual histology enabled through cytoplasm-specific X-ray stain for microscopic and nanoscopic computed tomography. Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2293-2298. doi: 10.1073/pnas.1720862115. Epub 2018 Feb 20. PMID: 29463748
Müller M, Kimm MA, Ferstl S, Allner S, Achterhold K, Herzen J, Pfeiffer F, Busse M. Nucleus-specific X-ray stain for 3D virtual histology. Sci Rep. 2018 Dec 14;8(1):17855. doi: 10.1038/s41598-018-36067-y. PMID: 30552357
Kazmierczak PM, Burton NC, Keinrath G, Hirner-Eppeneder H, Schneider MJ, Eschbach RS, Heimer M, Solyanik O, Todica A, Reiser MF, Ricke J, Cyran CC. Integrin-targeted quantitative optoacoustic imaging with MRI correlation for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma. PLoS One. 2018 Oct 3;13(10):e0204930. doi: 10.1371/journal.pone.0204930. eCollection 2018. PMID: 30281669
The experimental radiology group gratefully acknowledges research funding by:
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