We aim to define genetically encrypted correlates of tumor angiogenesis and tumor cell proliferation that enables to decipher new molecular therapeutically tractable targets. Another focus of our group are immunotherapeutic approaches and their combination with anti-angiogenetic treatment.
The major challenge in battling the cancer problem is the fact that cancer is a collection of different, constantly evolving genetic diseases. During tumor development incipient cancer cells undergo a multistep mutational process, during which they acquire a set of genetic and/or epigenetic lesions, which ultimately result in the cancerous state. These mutations provide the cancer cell with a set of traits that have been termed the ‘hallmarks of cancer’ – potential for unlimited proliferation, mitogen-independence, escape from apoptotic signals, immune evasion, sustained angiogenesis, tissue invasion and ultimately metastasis (Hanahan and Weinberg, 2000). These cancer phenotypes are thought to be the consequence of gain of function of oncogenes or inactivation of tumor suppressor genes. Due to recent technological advances, such as next generation sequencing, we are beginning to understand the complex genetic changes that ultimately result in cancerous growth.
In our group we are applying chemical genetics and in vivoapproaches to investigate the molecular mechanisms that control tumor angiogenesis and tumor cell proliferation. Herein, we seek to define genetically encrypted correlates of tumor angiogenesis and tumor cell proliferation that enables to decipher new molecular therapeutically tractable targets. Another focus of our group are immunotherapeutic approaches and their combination with anti-angiogenetic treatment. We employ cell culture and syngeneic, autochthonous and other mouse models of various cancers such as lung cancer, breast cancer, lymphoma and sarcoma to study treatment combinations and mechanisms of actions and resistance. In doing so, we particularly focus on the effects of various treatment algorithms on the hosts immune system to decipher potential synergies with novel immunotherapies. We also aim to understand why only a minority of patients with certain cancers such as lung cancer respond to immunotherapy and why those that do respond become resistant to it. In the long term we hope to use synergistic, mechanistically plausible combination treatments together with immunotherapy to overcome these problems and translate our findings into patient care.
Our group aims to investigate the molecular mechanisms that regulate tumor angiogenesis. This knowledge in hand we will define new combined potentially synergistic drug combinations to improve response to targeted therapy. In detail we will address the following aims:
Mariappan, A., Soni, K., Schorpp, K., Zhao, F., Minakar, A., Zheng, X., Mandad, S., Macheleidt, I., Ramani, A., Kubelka, T., Dawidowski, M., Golfmann, K., Wason, A., Yang, C., Simons, J., Schmalz, H.G., Hyman, A.A., Aneja, R., Ullrich, R., Urlaub, H., Odenthal, M., Buttner, R., Li, H., Sattler, M., Hadian, K., and Gopalakrishnan, J. (2019). Inhibition of CPAP-tubulin interaction prevents proliferation of centrosome-amplified cancer cells. EMBO J 38.
Golfmann K, Meder L, Koker M, Volz C, Borchmann S, Tharun L, Dietlein F, Malchers F, Florin A, Buttner R, Rosen N, Rodrik-Outmezguine V, Hallek M, and Ullrich RT (2018). Synergistic anti-angiogenic treatment effects by dual FGFR1 and VEGFR1 inhibition in FGFR1-amplified breast cancer. Oncogene 37, 5682-5693.
Meder L, Konig K, Dietlein F, Macheleidt I, Florin A, Ercanoglu MS, Rommerscheidt-Fuss U, Koker M, Schon G, Odenthal M, Klein F, Buttner R, Schulte JH, Heukamp LC, and Ullrich RT (2018). LIN28B enhanced tumorigenesis in an autochthonous KRAS(G12V)-driven lung carcinoma mouse model. Oncogene 37, 2746-2756.
Meder L, Schuldt P, Thelen M, Schmitt A, Dietlein F, Klein S, Borchmann S, Wennhold K, Vlasic I, Oberbeck S, Riedel R, Florin A, Golfmann K, Schlosser HA, Odenthal M, Buttner R, Wolf J, Hallek M, Herling M, von Bergwelt-Baildon M, Reinhardt HC, and Ullrich RT (2018). Combined VEGF and PD-L1 blockade displays synergistic treatment effects in an autochthonous mouse model of small cell lung cancer. Cancer Res 10.1158/0008-5472.CAN-17-2176.
Zirkel A, Nikolic M, Sofiadis K, Mallm JP, Brackley CA, Gothe H, Drechsel O, Becker C, Altmuller J, Josipovic N, Georgomanolis T, Brant L, Franzen J, Koker M, Gusmao EG, Costa IG, Ullrich RT, Wagner W, Roukos V, Nurnberg P, Marenduzzo D, Rippe K, and Papantonis A (2018). HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types. Mol Cell 70, 730-744 e736.
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Targeting tumor angiogenesis
Clinic I of Internal Medicine - CMMC Research Building
CMMC - PI - assoc. RG 23
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+49 221 478 6882
Clinic I of Internal Medicine - CMMC Research Building
Kerpener Str. 62
50937 Cologne
https://innere1.uk-koeln.de/forschung/arbeitsgruppen-labore/krebstherapie-und-molekulare-bildgebung/
Lydia Meder, PhD, PostDoc
Sara Breid, PhD, PostDoc
Sven Borchmann, MD, PostDoc
Carolin Selenz, MSc, PhD-student
Marieke Nill, Technician
Mirjam Koker, BSc
Christoph Otto, MD student
Hanna Ludwig, MD student