Department for Translational Medical Oncology

Unique alterations within tumor cells can be targets for novel treatment approaches. Scientists of the department for Translational Medical Oncology are working on identifying pivotal gene alterations and cellular subtypes that are responsible for initiating or fueling tumor growth and metastasis formation. Within individual patient tumors, a small fraction of all cells drives long-term tumor growth and metastases. Targeting this tumor-initiating cells (TIC) activity is essential to improve the long-term outcome in advanced solid cancers. The lab has developed and extensively characterized a bank of primary in vitro and in vivo models derived from solid patient tumors, e.g. CRC, PDAC and sarcomas. These functionally and genetically heterogeneous models are utilized to identify therapy relevant alterations and synthetic lethal interactions, e.g. by large scale shRNA knockdown or overexpression screening approaches. Following functional testing of potential therapeutic target alterations, targeted therapeutic strategies are developed and translated into the clinic.

The Glimm Lab, represented by the Department of Translational Medical Oncology in Dresden and the Translational Functional Cancer Genomics group in Heidelberg, welcomes researchers at both NCT partner sites to join their expertise in collaborating on these research questions.

In an interdisciplinary approach, new discoveries are directly transferred into treatment recommendations using the NCT/DKTK MASTER registry trial. The NCT-MASTER (Molecularly Aided Stratification for Tumor Eradication) protocol consents young patients or patients with rare tumor diseases for molecular diagnostics approaches with the explicit purpose of evaluating and stratifying for the best molecular treatment strategy and enrolment in diagnostic and therapeutic clinical trials. The NCT MASTER is a joint NCT program between NCT Heidelberg and NCT/UCC Dresden. You can find more information about registering for the program here or download the flyer here.

The NCT/UCC Dresden Center for Personalized Oncology aims at translating latest research as well as innovative technologies and cancer therapies into clinical practice. A dedicated personalized oncology outpatient clinic provides consulting appointments to discuss innovative diagnostic approaches, results of genetic tumor profiling and molecularly guided treatment strategies. Clinical data and results of molecular analyses as well as potential therapeutic implications are discussed within a molecular tumor board participated by an interdisciplinary team of specialists in molecular diagnostics, targeted cancer therapy as well as involved clinical departments.

Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins. Considering that only around 2% of the human transcriptome is translated, ncRNAs represent a huge proportion of the DNA encoded genetic information. Many ncRNA subspecies have been described, for instance microRNAs, small nucleolar RNAs or long non-coding RNAs (lncRNAs). They play pivotal roles in a plethora of cellular processes in development and diseases, including cancer, and can interact with nearly all cellular components.
By exploring various cancer entities and state-of-the art techniques, we want to demonstrate that non-coding RNAs can drive tumorigenesis and influence anti-cancer treatment response. In addition, we will explore their suitability to function as biomarkers for precision oncology based approaches.

RESEARCH AIMS

• Identification and characterization of cancer-driving ncRNAs
• Characterization of ncRNA-epigenome landscapes in various cancers
• Defining prognostic ncRNA scores for different targeted cancer therapies
• Exploring therapy resistance associated ncRNAs

The department closely collaborates with the Mildred-Scheel-Group “Biomedical Genomics”, headed by Dr. Anna Poetsch, exploring the possibilities of novel functional genomics and machine learning approaches to investigate DNA-damage response mechanisms in cancer.

Head of Department

• Prof. Dr. med. Hanno Glimm, head of department, specialist for internal medicine, hematology and oncology, hanno.glimm(at)nct-dresden.de, +49 (0)351 458 5540

Administration

• Julia Dorok, team assistant, julia.dorok(at)nct-dresden.de, +49 (0)351 458 5527
• Yasmin Führer, secretary, yasmin.fuehrer(at)nct-dresden.de, +49 (0)351 458 5531
• Dr. Daniela Richter, administrative and scientific coordination, daniela.richter(at)nct-dresden.de, +49 (0)351 458 5539

Experimental Translational Oncology

• Dr. Claudia Ball, Senior Scientist, claudia.ball(at)nct-dresden.de
• Dr. Zunamys Carrero, PhD, Post-Doc, zunamys.carrero(at)nct-dresden.de
• Sara Hrabovska, PhD Student, sara.hrabovska(at)nct-dresden.de
• Melanie Hüther, Technical Assistant, melanie.huether(at)nct-dresden.de
• Dr. Attila Jady, Bioinformatician / Bioinformatiker, attila.jady(at)nct-dresden.de
• Gabriela Perreira dos Santos, PhD Student, gabriela.santos(at)nct-dresden.de
• Anne Morgenstern, Master Student, anne.morgenstern(at)nct-dresden.de
• Isabell Wolf, Technical Assistant, isabell.wolf(at)nct-dresden.de
• Niall Belton, Technical Assistant, niall.belton(at)nct-dresden.de

Clinical Translational Oncology

• Miriam Gediga, Resident physician (Rotation), miriam.gediga(at)nct-dresden.de
• Dr. med. Dorothea Hanf, Resident physician TMO, dorothea.hanf(at)nct-dresden.de
• Dr. med. Christoph Heining, Senior attending  physician, specialist for internal medicine, hematology and oncology, christoph.heining(at)nct-dresden.de
• Dr. med. Catrin List, Specialist for internal medicine, hematology and oncology, catrin.list(at)nct-dresden.de
• Dr. med. Lino Möhrmann, Resident physician TMO, lino.moehrmann(at)nct-dresden.de
• Sophia Nuck, Study Nurse, sophia.nuck(at)nct-dresden.de
• Susanne Uhlmann, Study Nurse, susanne.uhlmann(at)nct-dresden.de

Non-coding RNAs in Leukemia

• Dr. Marius Bill, Specialist for internal medicine, hematology and oncology, Mildred-Scheel-Group “Non-coding RNAs in Leukemia”, marius.bill(at)nct-dresden.de
• Silke Brilloff, Technical Assistant, Mildred-Scheel-Group “Non-coding RNAs in Leukemia”, silke.brilloff(at)nct-dresden.de
• Elahe Rahimian, PhD Student, Mildred-Scheel-Group “Non-coding RNAs in Leukemia”, elahe.rahimian(at)nct-dresden.de
• Silvia Schäfer, PhD Student, Mildred-Scheel-Group “Non-coding RNAs in Leukemia”, silvia.schaefer(at)nct-dresden.de
• Dr. Alexander Wurm, Group Leader, Mildred-Scheel-Group “Non-coding RNAs in Leukemia”, alexander.wurm(at)nct-dresden.de

Biomedical Genomics

• Dr. Anna Poetsch, Group Leader, Mildred-Scheel-Group “Biomedical Genomics”, anna.poetsch(at)tu-dresden.de
• CS Meera, PhD student, meera.chitra_satheesh(at)tu-dresden.de
• Sukrit Mahajan, PhD student, sukrit.mahajan(at)tu-dresden.de
• Yana Vassileva, MD/ Student of Computational Modeling and Simulation, MSNZ fellow, yana.vassileva1(at)mailbox.tu-dresden.de
• Jessica Do Amaral Andrade, Student of Computational Modeling and Simulation, jessica.do_amaral_andrade(at)mailbox.tu-dresden.de
• Kenza Garreau, Student of Computational Modeling and Simulation, kenza.garreau(at)mailbox.tu-dresden.de
• Michaela Unger, Student of Molecular Bioengineering
• Dmitrii Severinov, Student of Molecular Bioengineering, DAAD fellow, dmitrii.severinov(at)mailbox.tu-dresden.de
• Gloria Marchesi, Admin, gloria.marchesi(at)tu-dresden.de

Alumni

• Dr. med. Arne Jahn, resident physician (rotation), human genetics
• Dr. med. Theresa Kretschmann, Resident physician (Rotation), theresa.kretschmann(at)nct-dresden.de

Wahjudi LW, Bernhardt S, Abnaof K, Horak P, Kreutzfeldt S, Heining C, Borgoni S, Becki C, Berg D, Richter D, Hutter B, Uhrig S, Pfütze K, Leichsenring J, Glimm H, Brors B, von Kalle C, Stenzinger A, Korf U, Fröhling S, Wiemann S. Integrating proteomics into precision oncology. Int J Cancer. 2020 Sep 19. doi: 10.1002/ijc.33301. Online ahead of print

Laskin J, Liu SV, Tolba K, Heining C, Schlenk RF, Cheema P, Cadranel J, Jones MR, Drilon A, Cseh A, Gyorffy S, Solca F, Duruisseaux M. NRG1 fusion-driven tumors: biology, detection and the therapeutic role of afatinib and other ErbB-targeting agents. Ann Oncol. 2020 doi:  0.1016/j.annonc.2020.08.2335. Online ahead of print.

Cadranel J, Liu SV, Duruisseaux M, Branden E, Goto Y, Weinberg BA, Heining C, Schlenk RF, Cheema P, Jones MR, Drilon A, Trombetta D, Muscarella LA, Tolba K, Gounant V, Cseh A, Solca F, Laskin JJ, Renouf DJ. Therapeutic Potential of Afatinib in NRG1 Fusion-Driven Solid Tumors: A Case Series. Oncologist. 2020 Aug 27. doi: 10.163. Online ahead of print

Heilig CE, Horak P, Lipka DB, Mock A, Uhrig S, Kreutzfeldt S, Richter S, Gieldon L, Fröhlich M, Hutter B, Hübschmann D, Teleanu V, Schmier JW, Philipzen J, Beuthien-Baumann B, Schröck E, von Deimling A, Bauer S, Heining C, Mechtersheimer G, Stenzinger A, Brors B, Wardelmann E, Glimm H, Hartmann W, Fröhling S. Germline SDHB-inactivating mutation in gastric spindle cell sarcoma. Genes Chromosomes Cancer. 2020 Oct;59(10):601-608. doi: 10.1002/gcc.22876. Epub 2020 Jun 26.

Möhrmann, L.; Zowada, M. K.; Strakerjahn, H.; et al. A Perivascular Niche in the Bone Marrow Hosts Quiescent and Proliferating Tumorigenic Colorectal Cancer Cells. Int. J. Cancer 2020. https://doi.org/10.1002/ijc.32933.

Voronina, N.; Wong, J. K. L.; Hübschmann, D.; et al. The Landscape of Chromothripsis across Adult Cancer Types. Nat Commun 2020, 11 (1), 2320. https://doi.org/10.1038/s41467-020-16134-7.

Horak, P.; Uhrig, S.; Witzel, M.; et al. Comprehensive Genomic Characterization of Gene Therapy-Induced T-Cell Acute Lymphoblastic Leukemia. Leukemia 2020. https://doi.org/10.1038/s41375-020-0779-z.

Ronellenfitsch, M. W.; Harter, P. N.; Kirchner, M.; et al. Targetable ERBB2 Mutations Identified in Neurofibroma/Schwannoma Hybrid Nerve Sheath Tumors. J. Clin. Invest. 2020. https://doi.org/10.1172/JCI130787.

Weinberg, F.; Griffin, R.; Fröhlich, M.; et al. Identification and Characterization of a BRAF Fusion Oncoprotein with Retained Autoinhibitory Domains. Oncogene 2019. https://doi.org/10.1038/s41388-019-1021-1.

Tirier, S. M.; Park, J.; Preußer, F; et al. Pheno-Seq - Linking Visual Features and Gene Expression in 3D Cell Culture Systems. Sci Rep 2019, 9 (1), 12367. https://doi.org/10.1038/s41598-019-48771-4.

Gröschel, S.; Hübschmann, D.; Raimondi, F.; et al. Defective Homologous Recombination DNA Repair as Therapeutic Target in Advanced Chordoma. Nat Commun 2019, 10 (1), 1635. https://doi.org/10.1038/s41467-019-09633-9.

Wünsche, P.; Eckert, E. S. P.; Holland-Letz, T.; et al. Mapping Active Gene-Regulatory Regions in Human Repopulating Long-Term HSCs. Cell Stem Cell 2018, 23 (1), 132-146.e9. https://doi.org/10.1016/j.stem.2018.06.003.

Heining, C.; Horak, P.; Uhrig, S.; et al. NRG1 Fusions in KRAS Wild-Type Pancreatic Cancer. Cancer Discov 2018, 8 (9), 1087–1095. https://doi.org/10.1158/2159-8290.CD-18-0036.

Bormann, F.; Rodríguez-Paredes, M.; Lasitschka, F.; et al. Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis. Cell Rep 2018, 23 (11), 3407–3418. https://doi.org/10.1016/j.celrep.2018.05.045.

Perera-Bel, J.; Hutter, B.; Heining, C.; et al. From Somatic Variants towards Precision Oncology: Evidence-Driven Reporting of Treatment Options in Molecular Tumor Boards. Genome Med 2018, 10 (1), 18. https://doi.org/10.1186/s13073-018-0529-2.

Giessler, K. M.; Kleinheinz, K.; Huebschmann, D.; et al. Genetic Subclone Architecture of Tumor Clone-Initiating Cells in Colorectal Cancer. J. Exp. Med. 2017, 214 (7), 2073–2088. https://doi.org/10.1084/jem.20162017.

Dieter, S. M.; Glimm, H.; Ball, C. R. Colorectal Cancer-Initiating Cells Caught in the Act. EMBO Mol. Med. 2017, 9 (7), 856–858. https://doi.org/10.15252/emmm.201707858.

Horak, P.; Klink, B.; Heining, C.; et al. Precision Oncology Based on Omics Data: The NCT Heidelberg Experience. Int. J. Cancer 2017, 141 (5), 877–886. https://doi.org/10.1002/ijc.30828.

Ball, C. R.; Oppel, F.; Ehrenberg, K. R.; et al. Succession of Transiently Active Tumor-Initiating Cell Clones in Human Pancreatic Cancer Xenografts. EMBO Mol Med 2017, 9 (7), 918–932. https://doi.org/10.15252/emmm.201607354.

Dieter, S. M.; Giessler, K. M.; Kriegsmann, M.; et al. Patient-Derived Xenografts of Gastrointestinal Cancers Are Susceptible to Rapid and Delayed B-Lymphoproliferation. Int. J. Cancer 2017, 140 (6), 1356–1363. https://doi.org/10.1002/ijc.30561.

Weischenfeldt, J.; Dubash, T.; Drainas, A. P.; et al. Pan-Cancer Analysis of Somatic Copy-Number Alterations Implicates IRS4 and IGF2 in Enhancer Hijacking. Nat. Genet. 2017, 49 (1), 65–74. https://doi.org/10.1038/ng.3722.

Dubash, T. D.; Hoffmann, C. M.; Oppel, F.; et al. Phenotypic Differentiation Does Not Affect Tumorigenicity of Primary Human Colon Cancer Initiating Cells. Cancer Lett. 2016, 371 (2), 326–333. https://doi.org/10.1016/j.canlet.2015.11.037.

Horak, P.; Fröhling, S.; Glimm, H. Integrating Next-Generation Sequencing into Clinical Oncology: Strategies, Promises and Pitfalls. ESMO Open 2016, 1 (5), e000094. https://doi.org/10.1136/esmoopen-2016-000094.