Translationale Forschung

Die translationale Forschung studiert und überträgt Erkenntnisse aus der Laborforschung in die klinische Praxis und umgekehrt. Sie bildet daher einen zentralen Teil der Innovation zu Fortschritten in Diagnose und Behandlung von bösartigen Erkrankungen.

Unter dem Dach des Cancer Center Zürich arbeiten zur Zeit die folgende Forschungsgruppen:

Balgrist University Hospital

Balgrist University Hospital - Dr. med. Daniel Müller

Group Leader

Dr. Unai Silvan
Dr. med. Daniel A. Müller

Müller_Daniel_Sarkom.png
 

Name of Institution

Laboratory for Cancer Biomechanics
Department of Orthopaedics
University of Zürich
Balgrist Campus
Lengghalde 5
CH-8008 Zürich
Tel:  +41 (44) 386 57 74
Fax: +41 (44) 386 11 09
daniel.mueller@balgrist.ch

Group Members
Adam Sabile, Senior scientist
Matthias Artl, Senior scientist
Knut Husmann, Senior scientist
Sander Botter, Senior scientist, Director of the Biobank
Eric Parigoris, Master student

Research focus

Orphan diseases, i.e. medical conditions with low prevalence in population, are frequently ignored in biomedical research because of difficulties in obtaining specimens and insufficient interest from funding agencies. However, the burden caused by these diseases, especially when they affect vulnerable segments of society, is huge. This is the case of bone cancers, an heterogeneous group of rare malignancies that display high mortality rates and have peak incidence in children and adolescents. Our research focuses on Osteosarcoma (OS), Ewing's Sarcoma (ES) and Chondrosarcoma (CS), which together account for nearly 80% of all bone tumor cases. We aim to identify new minimally invasive biomarkers for the diagnosis, prognosis and treatment monitoring of these tumors making use of the so-called 'liquid-biopsy'. In addition to genetic markers, such as circulating tumor DNA, we explore as well the possibility of using the biomechanical properties of metastasizing cancer cells (circulating tumor cells or CTCs) as predictive factor.

Keywords

Sarcoma, bone cancer, liquid biopsy, circulating tumor DNA, metastasis, biomechanics

5 Selected Publications

Silván U, Díez-Torre A, Bonilla Z, Moreno P, Díaz-Núñez M, Aréchaga J. Vasculogenesis and angiogenesis in nonseminomatous testicular germ cell tumors. Urol Oncol. 2015;33:268.e17-28

Silván U, Díez-Torre A, Jiménez-Rojo L, Aréchaga J. Vascularization of testicular germ cell tumours: evidence from experimental teratocarcinomas. (2010) Int J Androl 2010;33:765-774

Blache U, Silván U, Plodinec M, Suetterlin R, Jakob R, Klebba I, Bentires-Alj M, Aebi U, Schoenenberger CA. A tumorigenic actin mutant alters fibroblast morphology and multicellular assembly properties. Cytoskeleton (Hoboken). 2013;70:635-650

Goedecke N, Bollhalder M, Bernet R, Silvan U, Snedeker J. Easy and Accurate Mechano-profiling on Micropost Arrays. J Vis Exp. 2015;105

Silván U, Díez-Torre A, Arluzea J, Andrade R, Silió M, Aréchaga J. Hypoxia and pluripotency in embryonic and embryonal carcinoma stem cell biology. Differentiation. 2009;78(2-3):159-168

Funding

UZH, Universitätsklinik Balgrist

URL

https://www.balgrist.ch/forschung-lehre/forschung-orthopaedie/forschung-tumoren/


Department of Dermatology

Department of Dermatology - Prof. Dr. Reinhard Dummer
Department of Dermatology - Prof. Dr. Mitchell Levesque


Department of Gynecology

Department of Gynecology Research Laboratory - PD Dr. sc. nat. Manuel Stucki

Group Leader

PD Dr. sc. nat. Manuel Stucki
Stucki_Manuel.jpg

Name of Institution

Research laboratory
Department of Gynecology
University Hospital Zurich & University of Zurich
Wagistrasse 14
CH-8952 Schlieren
+41 44 556 3040
manuel.stucki@usz.ch

Group Members

Pia Ahorner, PhD student
Diana Bundschuh, Technician
Juliane Hutmacher, MD
Alison Ribeiro, PhD
Elefterios Pierre Samartzis, MD
Ioanna-Eleni Symeonidou, PhD

Research focus

Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5 year overall survival rate of only 40%. On the molecular level OC is a very heterogeneous disease but in some subtypes specific genetic mutations frequently occur. These include BRCA1/2 mutations in hereditary breast and ovarian carcinoma syndrome and ARID1A mutations in ovarian clear cell carcinoma and endometrioid ovarian carcinoma.

In order to design novel treatment approaches for these malignancies we use small molecule compound libraries and high-content screening techniques to systematically search for specific vulnerabilities in BRCA1/2- and ARID1A-deficient OC. In a next step we plan to evaluate promising hits on in vitro and in vivo OC model systems with the goal to rapidly translate our findings to the clinic for an improved management of this currently difficult-to-treat disease.

Keywords

Ovarian cancer, ovarian clear cell carcinoma, BRCA1/2, ARID1A, small molecule compound libraries, high-content screening

5 Selected Publications

Samartzis EP, Gutsche K, Dedes KJ, Fink D, Stucki M, Imesch P. Loss of ARID1A expression sensitizes cancer cells to PI3K- and AKT-inhibition. Oncotarget 2014; 5(14):5295–5303.

Larsen DH, Hari F, Clapperton JA, Gwerder M, Gutsche K, Altmeyer M, Jungmichel S, Toledo LI, Fink D, Rask MB, Gr¢fte M, Lukas C, Nielsen ML, Smerdon SJ, Lukas J, Stucki M. The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage. Nat Cell Biol. 2014;16(8):792-803.

Koppensteiner R, Samartzis EP, Noske A, vonTeichman A, Dedes I, Gwerder M, Imesch P, Ikenberg K, Moch H, Fink D, Stucki M, Dedes KJ. Effect of MRE11 loss on PARP-inhibitor sensitivity in endometrial cancer in vitro. PloS One 2014 9(6), e100041.

Corpet A, Olbrich T, Gwerder M, Fink D, Stucki, M. Dynamics of histone H3.3 deposition in proliferating and senescent cells reveals a DAXX-dependent targeting to PML-NBs important for pericentromeric heterochromatin organization. Cell Cycle 2014; 13(2):249–267.

Samartzis EP, Samartzis N, Noske A, Fedier A, Caduff R, Dedes KJ, Fink D, Imesch P. Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation? Mod Pathol. 2012 ;25(6):885-92.

Funding

Swiss National Science Foundation, Horten Stiftung, EMDO Stiftung, Promedica Stiftung, Vontobel Stiftung, Krebsliga Zürich, Julius Müller Stiftung, Hartmann Müller Stiftung, Olga Mayenfisch Stiftung, University of Zurich

URL

http://www.gynaekologie.usz.ch/forschung/Seiten/default.aspx


Department of Neurology

Laboratory of Molecular Neuro-Oncology - Prof. Dr. med. Michael Weller

Group Leader

Prof. Dr. med. Michael Weller
weller_M.jpg

Contact Information

Laboratory of Molecular Neuro-Oncology
Department of Neurology
University Hospital Zurich & University of Zurich
Frauenklinikstrasse 26
CH-8091 Zurich
+41 44 255 5500
michael.weller@usz.ch

Group Members

Caroline von Achenbach, PhD student
Sarah von Arb, Technician
Birthe Lohmann, PhD student
Silvia Dolski, Technician
Julia Friesen, Technician
Dorothee Gramatzki, MD
Caroline Hertler, MD
Davide Mangani, PhD student
Eleanna Papa, PhD student
Hannah Schneider, PhD
Katharina Seystahl, MD
Emese Szabo, PhD
Elisa Ventura, PhD student
Fabian Wolpert, MD

Research focus

Despite multimodal treatment of surgery, radiotherapy and chemotherapy, the prognosis for patients with malignant brain tumors, notably glioblastoma, remains poor. To design novel treatment approaches, we study the molecular pathways that are deregulated in glioblastoma and try to exploit metabolic abnormalities specific to cancer cells. Further, we study the microenvironment of brain tumors and explore how invasiveness and angiogenesis in brain tumors are regulated by the hosts`s brain. Further, our immunotherapy projects aim at defining the basis for novel approaches targeting glioma-initiating cells with stem cell properties, commonly named glioma stem cells.

Keywords

Glioblastoma, brain tumor, stem cells, angiogenesis, immunology

5 Selected Publications

Ahmad A, Frei K, Willscher E, Stefanski A, Kaulich K, Roth P, Stühler K, Reifenberger G, Binder H, Weller M. How stem-like are sphere cultures from long-term cancer cell lines: lessons from mouse glioma models. J Neuropathol Exp Neurol 2014;73:1062-1077

Frei K, Gramatzki D, Tritschler I, Schroeder JJ, Espinoza L, Rushing EJ, Weller M. Transforming growth factor-β pathway activity in glioblastoma. Oncotarget 2015;6:5963-5977

Mangani D, Weller M, Seyed Sadr E, Willscher E, Seystahl K, Reifenberger G, Tabatabai G, Binder H, Schneider H. Limited role for transforming growth factor-β pathway activation-mediated escape from VEGF inhibition in murine glioma models. Neuro-Oncology 2016;18:1610-1621

Seystahl K, Tritschler I, Szabo E, Tabatabai G, Weller M. Differential regulation of TGF-β-induced, ALK-5-mediated VEGF release by SMAD2/3 versus SMAD1/5/8 signaling in glioblastoma. Neuro-Oncology 2015;17:254-265

Weller M, Weber RG, Willscher E, Riehmer V, Hentschel B, Kreuz M, Felsberg J, Beyer U, Löffler-Wirth H, Kaulich K, Steinbach J, Hartmann C, Gramatzki D, Schramm J, Westphal M, Schackert G, Simon M, Martens T, Boström J, Hagel C, Sabel M, Krex D, Tonn JC, Wick W, Noell S, Schlegel U, Radlwimmer B, Pietsch T, Loeffler M, von Deimling A, Binder H, Reifenberger G, for the German Glioma Network. Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol 2015;129:679–693

Funding

Swiss National Science Foundation, Swiss Cancer League, Koetser Foundation, Wilhelm Sander Foundation, German Research Foundation, University of Zurich

URL

http://www.neurologie.usz.ch/forschung/seiten/neuro-onkologie.aspx

Laboratory of Molecular Neuro-Oncology - PD Dr. Patrick Roth

Group Leader

PD Dr. Patrick Roth
Roth_P.png

Name of Institution

Laboratory of Molecular Neuro-Oncology
Department of Neurology
University Hospital Zurich
Frauenklinikstrasse 26
CH-8091 Zurich
+41 44 255 5511
patrick.roth@usz.ch

Group Members

Lena Hänsch, PhD student
Alex Papachristodoulou, PhD student
Manuela Silginer, PhD
Christina Stadler, MD
Tobias Weiss, MD/PhD student

Research focus

The research of our group focuses on the biology of malignant gliomas. These tumors are characterized by resistance to conventional therapy and are paradigmatic for tumor-associated immunosuppression. Various in vitro and in vivo models have been established to address these issues. We are investigating the interaction of glioma cells and the immune system with a focus on immunosuppressive mechanisms. Current projects aim at exploring novel immunotherapeutic strategies against gliomas including CAR T cells and immune checkpoint inhibitors. Finally, we are interested in investigating novel therapeutic approaches in order to overcome the treatment resistance of these tumors.

Keywords

Brain cancer, glioblastoma, immunotherapy, novel drugs, CAR T cells

5 Selected Publications

Silginer M, Nagy S, Happold C, Schneider H, Weller M, Roth P. Autocrine activation of the IFN signaling pathway may promote immune escape in glioblastoma. Neuro Oncol, in press

Roth P, Valavanis A, Weller M. Long-term control and partial remission after initial pseudoprogression of glioblastoma by anti-PD-1 treatment with nivolumab. Neuro Oncol 2017;19:454-456

Silginer M, Burghardt I, Gramatzki D, Bunse L, Leske H, Rushing EJ, Hao N, Platten M, Weller M, Roth P. The aryl hydrocarbon receptor links integrin signaling to the TGF-b pathway. Oncogene 2016;35:3260-3271

Wick W, Gorlia T, Bady P, Platten M, van den Bent MJ, Taphoorn MJB, Steuve J, Brandes AA, Hamou MF, Wick A, Kosch M, Weller M, Stupp R, Roth P, Golfinopoulos V, Frenel JS, Campone M, Ricard D, Marosi C, Villa S, Weyerbrock A, Hopkins K, Homicsko K, Lhermitte B, Pesce G, Hegi ME. Phase II study of radiotherapy and temsirolimus versus radiochemotherapy with temozolomide in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation (EORTC 26082). Clin Cancer Res 2016;22:4797-4806

Codo P, Weller M, Meister G, Szabo E, Steinle A, Wolter M, Reifenberger G, Roth P. MicroRNA-mediated down-regulation of NKG2D ligands contributes to glioma immune escape. Oncotarget 2014;5:7651-7662

Funding

Swiss National Science Foundation, Swiss Cancer League, EMDO Foundation, Kurt und Senta Herrmann Stiftung, Novartis Stiftung für medizinisch-biologische Forschung

URL

http://www.neurologie.usz.ch/forschung/Seiten/neuro-onkologie.aspx#team


Department of Oncology

Laboratory of Molecular and Proteomic Oncology - Dr. Ferdinando Cerciello

Group

Ferdinando Cerciello, MD, PhD
Cerciello.jpg

Name of Institution

Laboratory for Molecular and Proteomic Oncology
Department of Oncology
University Hospital Zurich
Raemistrasse 100
CH-8091 Zurich
ferdinando.cerciello@usz.ch

Group Members

TBA

Research focus

Our focus is on clinical and translational mass spectrometry based proteomics for thoracic cancer. We investigate proteins as the key elements to translate phenotype of thoracic malignancies into clinical applications. In particular, we are interested in: 1. Multiplexed proteomics biomarkers for detection and monitoring of thoracic malignancies in blood, especially malignant pleural mesothelioma cancer; 2. Networks of protein-protein interactions  for novel candidate drug targets in thoracic cancer; 3. Integrative genotype and protein phenotype analysis for treatment decisions in thoracic cancer.

Keywords

Thoracic cancer, proteomics, mass spectrometry, mesothelioma

5 Selected Publications

Van Eyk JE, Corrales FJ, Aebersold R, Cerciello F, Deutsch EW, Roncada P, Sanchez JC, Yamamoto T, Yang P, Zhang H, Omenn GS. "Highlights of the Biology and Disease-driven Human Proteome Project, 2015-2016", J Proteome Res. 2016 Sep 20.

Bausch-Fluck D, Hofmann A, Bock T, Frei AP, Cerciello F, Jacobs A, Moest H, Omasits U, Gundry, RL, Yoon C, Schiess R, Schmidt A, Mirkowska P, Härtlová A, Van Eyk JE, Bourquin JP, Aebersold R, Boheler KR, Zandstra P, Wollscheid B. "A mass spectrometric-derived cell surface protein atlas", PLoS One. 2015 Apr 20;10(3).

Cerciello, F, Choi, M, Nicastri, A, Bausch-Fluck, D, Ziegler, A, Vitek, O, Felley-Bosco, E, Stahel, R, Aebersold, R, Wollscheid, B, "Identification of a seven glycopeptide signature for malignant pleural mesothelioma in human serum by selected reaction monitoring", Clin Proteomics 2013 Nov 8;10(1):16.

Hüttenhain, R, Surinova, S, Ossola, R, Sun, Z, Campbell, D, Cerciello, F, Schiess, R, Bausch-Fluck, D, Rosenberger, G, Chen J, Rinner, O, Kusebauch, U, Hajdúch, M, Moritz, RL, Wollscheid, B, Aebersold, R, "N-Glycoprotein SRMAtlas: a resource of mass-spectrometric assays for N-glycosites enabling consistent and multiplexed protein quantification for clinical applications", Mol Cell Proteomics. 2013 Apr;12(4):1005-16.

Ziegler*, A, Cerciello*, F, Bigosch, C, Bausch-Fluck, D, Felley-Bosco, E, Ossola, R, Soltermann, A, Stahel, RA, Wollscheid, B, "Proteomic Surfaceome Analysis of Mesothelioma", Lung Cancer. 2012 Feb;75(2):189-96 (* Ziegler, A. and Cerciello, F. contributed equally to the work).

Funding

Former grants ad personam: Swiss National Science Foundation, the Paul P. Carbone Lung Cancer Translational Research Award, Huggenberger-Bischoff Stiftung für Krebsforschung


Department of Otolaryngology, Head & Neck Surgery

Head & Neck Surgical Oncology - PD Dr. med. Gerhard F. Huber, MSc

Group Leader

PD Dr. med. Gerhard F. Huber, MSc
huber_g2.bmp

Name of Institution

Head & Neck Surgical Oncology
Department of Otolaryngology, Head & Neck Surgery
University Hospital Zurich
Frauenklinikstrasse 24
CH-8091 Zurich
+41 44 255 11 11
gerry.huber@usz.ch

Group Members

Yanic Ammann, MSc
Jonas Fellmann, MD
Roman D. Laske, MD
Christian Meerwein, MD
Grégoire B. Morand, MD, MSc
Cosima Riemenschnitter, MD
Domenic Vital, MD
Jonas Werner, BSc

Research focus

The research performed by our group focuses on investigating prognostic factors in head and neck squamous cell carcinoma. The overreaching goal of our research is to become able to predict the aggressiveness of a particular tumor and to offer a therapy tailored for every patients specific needs. Several retrospective projects are focusing on clinicopathological variables associated with a poorer outcome. Furthermore, a prospective study proposes to isolate and characterize the role of cancer stem cell subpopulations in head & neck squamous cell carcinoma. These projects are conducted in collaboration with the department of surgical pathology.

Another productive collaboration with the department of nuclear medicine investigates the diagnostic accuracy of several innovative imaging technologies in head and neck cancer. Our group recently received support from the "Innovationspool" of University of Zurich for one of his projects.

Keywords

Head & neck squamous cell carcinoma, stem cells, prognostic marker, sentinel lymph node biopsy

5 Selected Publications

Vital D, Morand GB, Meerwein C, Laske RD, Steinert HC, Schmid C, Brown ML, Huber GF. Early Timing of Thyroidectomy for Hyperthyroidism in Graves' Disease Improves Biochemical Recovery. World J Surg. 2017 Jul 5.

Meerwein CM, Sekine T, Veit-Haibach P, Bredell MG, Huber GF, Huellner MW. Multi-slice SPECT/CT vs. lymphoscintigraphy and intraoperative gamma ray probe for sentinel node mapping in HNSCC. Eur Arch Otorhinolaryngol. 2017 Mar;274(3):1633-1642.

Morand GB, Fellmann J, Laske RD, Weisert JU, Soltermann A, Zbinden R, Probst R, Huber GF. Detection of Helicobacter pylori in patients with head and neck cancer: Results from a prospective comparative study combining serology, polymerase chain reaction, and rapid urease test. Head Neck. 2016 May;38(5):769-74.

Rössle M, Weber CS, Züllig L, Graf N, Jochum W, Stöckli SJ, Moch H, Huber GF. EGFR expression and copy number changes in low T-stage oral squamous cell carcinomas. Histopathology. 2013 Aug;63(2):271-8. doi: 10.1111/his.12175. Epub 2013 Jun 13.

Züllig L, Roessle M, Weber C, Graf N, Haerle SK, Jochum W, Stoeckli SJ, Moch H, Huber GF. High sex determining region Y-box 2 expression is a negative predictor of occult lymph node metastasis in early squamous cell carcinomas of the oral cavity. Eur J Cancer. 2013 May;49(8):1915-22

Funding

University of Zurich, Innovationspool University of Zurich

URL

http://www.orl.usz.ch/forschung/seiten/orl-onkologie.aspx


Department of Radiation Oncology

Laboratory of Applied Radiation Biology - Prof. Dr. sc nat. Martin Pruschy

Group Leader

Prof. Dr. sc nat. Martin Pruschy
Pruschy.jpg

Name of Institution

Laboratory of Applied Radiation Biology
Department of Radiation Oncology
University Hospital Zurich & University of Zurich
Raemistr. 100
CH-8091 Zurich
+41 44 255 8549
martin.pruschy@usz.ch

Group Members

Lucas Basler, MD
Sabine Bender, PhD student
Angela Broggini-Tenzer, PhD
Simon Deycmar, PhD student
Erica Faccin Technician
Ivo Grgic, PhD student
Tamara Kazimova, PhD student
Ashish Sharma, PhD
Fabienne Tschanz, Ms student

Research focus

The insult on the level of DNA is most important for the cytotoxicity of radiotherapy. However radiotherapy also affects multiple cellular components that induce a multilayered stress response in the tumor. These processes co-determine the treatment sensitivity of the tumor and eventually treatment outcome. In close collaboration with the clinics and the pharmaceutical industry, we aim to identify treatment-activated rescue mechanisms of the tumor and to determine the radiosensitizing potential of clinically-relevant chemotherapeutical compounds. Both mechanistic and efficacy-oriented endpoints are investigated, using representative small animal tumor models and a small animal image-guided radiotherapy platform.  Further, and as part of a strong collaboration with the Proton Radiotherapy Center at the PSI, we investigate the biological response of the tumor and the normal tissue to different modalities of ionizing radiation towards a more personalized approach of radiotherapy taking also biological parameters into account.

Keywords

Radiotherapy, ionizing radiation, combined treatment modalities, signal transduction, angiogenesis, immunology

5 Selected Publications

Angela Broggini-Tenzer, Ashish Sharma, Katarzyna J. Nytko, Van Vuong, Katrin Orlowski, Daniel Hug, Terence O'Reilly, Martin Pruschy. Combined Treatment Strategies for Microtubule Stabilizing Agent-Resistant Tumors. Journal of National Cancer Institute, JNCI, 2015; 107(4): dju504.

Ashish Sharma, Sabine Bender, Oliver Riesterer, Angela Broggini-Tenzer and Martin Pruschy. Secretome signature identifies ADAM17 as a Novel Target for Radiosensitization of Non–Small Cell Lung Cancer. Clin Cancer Res. 2016; 22:4428-39.

Nytko KJ, Grgic I, Bender S, Ott J, Guckenberger M, Riesterer O, Pruschy M. The hypoxia-activated prodrug evofosfamide in combination with multiple regimens of radiotherapy. Oncotarget. 2017;8:23702-23712.

Shen CJ, Sharma A, Vuong DV, Erler JT, Pruschy M, Broggini-Tenzer A. Ionizing radiation induces tumor cell lysyl oxidase secretion. BMC Cancer. 2014 Jul 22;14:532.

Andrea Fontana, Marc Augsburger, Nicole Grosse, Tony Lomax, Alessandro A. Sartori, Martin Pruschy. Differential Requirements for homologous recombination repair and non-homologous end joining after high-ebergy proton and photon irradiation. Radiotherapy and Oncology, 2015;116:374-80.

Funding

Swiss National Science Foundation, Swiss Cancer League, Horizon2020

URL

http://www.radio-onkologie.usz.ch/forschung/Seiten/angewandte-strahlenbiologie.aspx

Medical Physics Research Group Radiomics - Dr. sc. nat. Stephanie Tanadini-Lang

Group Leader

Dr. sc. nat. Stephanie Tanadini-Lang
Tanadini-Lang.jpg

Name of Institution

Medical Physics Research Group Radiomics
Department of Radiation Oncology
University Hospital Zurich & University of Zurich
Rämistrasse 100
CH-8091 Zurich
+41 44 255 1111
stephanie.tanadini-lang@usz.ch

Group Members

Marta Nesteruk, PhD student
Alex Vils, Master student
Matea Pavic, MD
Christina Schröder
Sabrina Stark Schneebeli, PhD

Research focus

Cancer is a heterogeneous disease in regard to etiology, pathogenesis, therapy response and prognosis and consequently, response to therapy varies among patients and also within patients. For optimization and individualization of treatment strategies, identification of biomarkers is therefore essential. Imaging biomarkers (Radiomics) are of special interest as they provide spatial information on tumor biology (intra-patient variability) and are acquired non-invasively. Using our in-house developed Software we can extract about 700 radiomic features describing tumor shape, tumor intensity and tumor texture from medical images. These radiomic features are currently investigated regarding their value for outcome modelling and for correlation to the tumor biology.

Keywords

Radiomics, imaging biomarkers, outcome modelling

5 Selected Publications

Nesteruk, M., Lang, S., Veit-Haibach, P., Studer, G., Stieb, S., Glatz, S., ... & Guckenberger, M. (2015). Tumor stage, tumor site and HPV dependent correlation of perfusion CT parameters and [18F]-FDG uptake in head and neck squamous cell carcinoma. Radiotherapy and Oncology, 117(1), 125-131.

Bogowicz, M., Riesterer, O., Bundschuh, R., Veit-Haibach, P., Huellner, M., Studer, G., Stieb, S., Glatz, S., Pruschy, M., Guckenberger, M., Tanadini-Lang, S. Stability of radiomic features in CT perfusion maps. Physics in Medicine and Biology, 61(24), 8736

Tanadini-Lang, S., Rieber, J., Filippi, A. R., Fode, M. M., Streblow, J., Adebahr, S., ... & Eble, M. J. (2017). Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease. Radiotherapy and Oncology.

Riesterer, O., Nesteruk, M., Studer, G., Guckenberger, M., & Lang, S. (2016). Predictive Value of Radiomics Analysis for Local Tumor Control After Radiochemotherapy in Patients With Head and Neck cancer. International Journal of Radiation Oncology• Biology• Physics, 96(2), S117.

Zwanenburg, A., Leger, S., Vallières, M., & Löck, S. (2016). Image biomarker standardisation initiative-feature definitions. arXiv preprint arXiv:1612.07003.

Funding

Swiss National Science Foundation, University of Zurich

URL

http://www.radio-onkologie.usz.ch/forschung/seiten/forschungsgruppe-physik.aspx

Research Group Stereotactic Radiotherapy - Prof. Dr. Matthias Guckenberger

Group Leader

Prof. Dr. Matthias Guckenberger
guckenberger_matthias.jpg

Co-GL: PD. Dr. Nicolaus Andratschke
Co-GL: Dr. Stephanie Tanadini-Lang

Name of Institution

Department of Radiation Oncology
University Hospital Zurich & University of Zurich
Raemistr. 100
CH-8091 Zurich
+41 44 255 2930
Matthias.Guckenberger@usz.ch 

Group Members

Stephanie Kroeze, MD
Corinna Fritz, MD
Matea Pavic, MD
Lukas Basler, MD
Jerome Krayenbühl, PhD
Stefanie Ehrbar, MSc
Antonia Schiess
Sarah Keppner
Indira Madani

Research focus

The practice of Radiation Oncology has changed fundamentally in the recent years in particular due to advances in technology. Stereotactic radiotherapy today allows focused irradiation with ablative irradiation doses. Our research group addresses the technological, biological and clinical implications of stereotactic radiotherapy as well as Proton radiotherapy.

Keywords

Radiotherapy, ionizing radiation, stereotactic radiotherapy, response modelling, biomarker research, Proton radiotherapy

5 Selected Publications

Nomogram based overall survival prediction in stereotactic body radiotherapy for oligo-metastatic lung disease. Tanadini-Lang S, Rieber J, Filippi AR, Fode MM, Streblow J, Adebahr S, Andratschke N, Blanck O, Boda-Heggemann J, Duma M, Eble MJ, Ernst I, Flentje M, Gerum S, Hass P, Henkenberens C, Hildebrandt G, Imhoff D, Kahl H, Klass ND, Krempien R, Lohaus F, Petersen C, Schrade E, Wendt TG, Wittig A, Høyer M, Ricardi U, Sterzing F, Guckenberger M. Radiother Oncol. 2017 May;123(2):182-188

Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: A systematic review. Kroeze SG, Fritz C, Hoyer M, Lo SS, Ricardi U, Sahgal A, Stahel R, Stupp R, Guckenberger M. Cancer Treat Rev. 2017 Feb;53:25-37.

Stereotactic body radiotherapy for oligo-metastatic liver disease - Influence of pre-treatment chemotherapy and histology on local tumor control. Klement RJ, Guckenberger M, Alheid H, Allgäuer M, Becker G, Blanck O, Boda-Heggemann J, Brunner T, Duma M, Gerum S, Habermehl D, Hildebrandt G, Lewitzki V, Ostheimer C, Papachristofilou A, Petersen C, Schneider T, Semrau R, Wachter S, Andratschke N. Radiother Oncol. 2017 May;123(2):227-233.

Validation of dynamic treatment-couch tracking for prostate SBRT. Ehrbar S, Schmid S, Jöhl A, Klöck S, Guckenberger M, Riesterer O, Tanadini-Lang S. Med Phys. 2017 Mar 24.

Respiratory motion-management in stereotactic body radiation therapy for lung cancer - A dosimetric comparison in an anthropomorphic lung phantom (LuCa). Ehrbar S, Perrin R, Peroni M, Bernatowicz K, Parkel T, Pytko I, Klöck S, Guckenberger M, Tanadini-Lang S, Weber DC, Lomax A. Radiother Oncol. 2016 Nov;121(2):328-334.

Funding

Swiss National Science Foundation, Swiss Cancer League, SAMW, Varian

URL

http://www.radio-onkologie.usz.ch/fachwissen/stereotaxie/Seiten/default.aspx


Department of Urology

Oncology Section of Urology – PD Dr. med Maurizio Provenzano, PhD

Group Leader

PD Dr. med. Maurizio Provenzano, PhD
Provenzano.png

Name of Institution

Department of Urology, Oncology Section
University Hospital Zurich & University of Zurich
Wagistrasse 21
CH-8952 Schlieren
+41 79 578 86 26
Maurizio.provenzano@usz.ch

Group Members

Abdou Allayeh, PhD, Postdoc
Etienne X Keller, MD
Mykhailo Razumenko, PhD, Postdoc
Gabriele Chiffi, Master student

Research focus

To study the complex interactions between the immune system and prostate cancer we engage in three specific projects:

Banking of human antibody repertoires for therapeutic use: The main aim of this CTI project in collaboration with MEMO therapeutics is to establish a library ("antibody bank") of human antibody repertoires of individuals that have successfully mastered a disease. The comparison of the BKPyV-specific antibody repertoire in patients vs. healthy donors is expected to yield insights into the immune defense mechanisms that are required to control BKPyV-related diseases.

Prostate cancer-specific bispecific antibodies (biAbs) to prevent and treat prostate cancer: We are currently studying the interaction of a bispecific antibody, the TCT001 (STEAP1 x CD3 bsAb) with multiple malignant prostate cancer subpopulations to treat this cancer. The combinatory treatment with an additional tool for co-stimulatory activation (TCT002, EpCAM x CD28 bsAb) will enhance cytotoxic effects.

The indoleamine 2, 3-dioxygenase (IDO) as marker for prostate cancer diagnosis: IDO is an enzyme that degrades the essential amino acid tryptophan, thus inhibiting T cell proliferation and activity. It is predominantly induced in inflammatory environments. We were the first group proving the potential use of IDO as a marker in prostate cancer.

Keywords

Prostate Cancer, BK polyomavirus, Biomarkers, adaptive immune surveillance, bispecific antibodies

5 Selected Publications

Provenzano M, Allayeh AK. Harnessing systemic immune responses for polyomavirus BK involvement in cancer development and progression. Cytokine, 2017, 96: 273

Keller XE, Kardas P, Acevedo C, Sais G, Poyet C, Banzola I, Mortezavi A, Seifert B, Sulser T, Hirsch HH, Provenzano M. Antibody response to BK polyomavirus as a prognostic biomarker and potential therapeutic target in prostate cancer. Oncotarget. 2015 Mar 20; 6 (8):6459-69.

Lacher MD, Provenzano M. Cancer T cell immunotherapy with bispecific antibodies and chimeric antigen receptors. Recent Pat Anticancer Drug Discov. 2013 Sep; 8(3):239-54. Review.

Sais G, Wyler S, Hudolin T, Banzola I, Mengus C, Bubendorf L, Wild PJ, Hirsch HH, Sulser T, Spagnoli GC, Provenzano M. Differential patterns of large tumor antigen-specific immune responsiveness in patients with BK polyomavirus-positive prostate cancer or benign prostatic hyperplasia. J Virol. 2012 Aug; 86(16):8461-71.

Feder-Mengus Ch, Wyler SF, Hudolin T, Ruszat R, Bubendorf L, Chiarugi A, Pittelli M, Weber WP, Bachmann A, Gasser TC, Sulser T, Heberer M, Spagnoli CG, Provenzano M. High expression of indoleamine 2,3-dioxygenase gene in prostate cancer. Eur J Cancer, 2008, 44: 2266-2275

Funding

Commission for Technology and Innovation (CTI)
Proof-of-Concept Funding (UNITECTRA)
Stiftung für Urologische Forschung

URL

http://www.urologie.usz.ch/forschung/grundlagenforschung/provenzano/Seiten/default.aspx

http://www.asm.org/index.php/asm-journal-tipsheets/88-news-room/journal-tipsheets/8177-newevidence-for-polyomavirus-bk-role-in-prostate-cancer

http://www.uzh.ch/de/about/portrait/awards/annualprizes/2016/med.html

Urological Research - PD Dr. med. Daniel Eberli, PhD

Group Leader

PD Dr. med. Daniel Eberli, PhD
Eberli.png

Name of Institution

Department of Urology, Urological Research
University Hospital Zurich & University of Zurich
Wagistrasse 21
CH-8952 Schlieren
+41 44 255 95 49
Daniel.Eberli@usz.ch

Group Members

Daniel Keller, PhD Student
Benedikt Kranzbühler, MD, Research Assistant
Deana Mohr, PhD, H2020 Project Manager and Coordinator
Jenny Prange, PhD, Postdoc
Souzan Salemi, PhD, Senior Postdoc
Jakub Smolar, PhD Student

Research focus

One focus of the group headed by PD Dr. Daniel Eberli is research on prostate cancer mechanisms. This research investigates the targeting of androgen receptor (AR) in combination with autophagy inhibitors for enhancement of the anti-tumor effect in castration resistant prostate cancer (CRPC) cells. Abiraterone (Abi) in combination with androgen deprivation therapy (ADT) agonists is an approved treatment for castration-resistant prostate cancer. Data implicates, that Abi not only leads to a decrease of circulating testosterone levels, but it also has inhibitory effects on the intratumoral synthesis of active androgens, which play a significant role in gaining resistance against conventional ADT. An additional mechanism of survival in prostate cancer cells during ADT is autophagy. We hypothesize that inhibition of intracellular androgen synthesis with Abi may lead to a more excessive up-regulation of autophagy.

Keywords

Prostate Cancer, Autophagy, Androgen deprivation

Selected Publications

Mortezavi A, Salemi S, Rupp NJ, Rüschoff JH, Hermanns T, Poyet C, Randazzo M, Simon HU, Moch H, Sulser T, Wild P, Eberli D. Negative LC3b immunoreactivity in cancer cells is an independent prognostic predictor of prostate cancer specific death. Oncotarget. 2017 May 9;8(19):31765-31774. doi: 10.18632/oncotarget.15986

Mortezavi A, Keller EX, Poyet C, Hermanns T, Saba K, Randazzo M, Fankhauser CD, Wild PJ, Moch H, Sulser T, Eberli D. Clinical impact of prostate biopsy undergrading in an academic and community setting. World J Urol. 2016 Oct;34(10):1481-90. doi: 10.1007/s00345-016-1788-4. Epub 2016 Mar 1.

Eberli D, Mortezavi A, Sulser T. [Focal therapy-a new era in the treatment of prostate cancer]. Praxis (Bern 1994). 2014 Mar 26;103(7):391-7. doi: 10.1024/1661-8157/a001607. German.

Stölting MN, Ferrari S, Handschin C, Becskei A, Provenzano M, Sulser T, Eberli D. Myoblasts inhibit prostate cancer growth by paracrine secretion of tumor necrosis factor-α. J Urol. 2013 May;189(5):1952-9. doi: 10.1016/j.juro.2012.10.071. Epub 2012 Oct 30.

Funding

Max & Hedwig Niedermayer Stiftung, Janssen Pharmaceutica LV, Horizon2020, Horten Foundation, SNF (Co-Applicant)

URL

http://www.urologie.usz.ch/forschung/grundlagenforschung/provenzano/Seiten/default.aspx


Department of Thoracic Surgery

Laboratory of Molecular Oncology - PD Dr. Emanuela Felley-Bosco

Group Leader

PhD PD Emanuela Felley-Bosco
felley-bosco-emanuela.jpg

Name of Institution

Laboratory of Molecular Oncology
Department of Thoracic Surgery
University Hospital Zurich & University of Zurich
Sternwartstrasse 14
CH-8091 Zurich
+41 44 255 2771
emanuela.felley-bosco@usz.ch

Group Members

Saskja Bühler, master student
Jelena Kresoja-Rakic, PhD
Manuel Ronner, Technician
Elia Roth, apprentice
Agata Trzcinski, nèe Okonska, PhD student

Research focus

Malignant pleural mesothelioma (MPM) is a cancer most often associated with the exposure to asbestos fibers. Despite the ban on the commercial use of asbestos in the early nineties, the incidence of MPM will continue to rise over the next decade in Western Europe because of the latency period of up to 40 years. The Division of Thoracic Surgery and the Clinic for Oncology at the University Hospital of Zürich are a major referral center for patients with MPM. Our laboratory has a longtime focus on translational research in this disease combining opportunities provided by the clinical activities with focused research efforts in translational and fundamental research projects. In particular, we aim at understanding on one hand mechanisms of mesothelioma development and on the other we study the molecular pathways that are deregulated in mesothelioma in order to design novel treatment approaches.

Keywords

Chronic inflammation-induced disease, mesothelioma, tumor initiating cells, mesothelioma therapy, chemotherapy resistance, tumor development, NF2, BAP1

5 Selected Publications

Parrotta R, Okonska A, Ronner M, Weder W, Stahel R, Penengo L, Felley-Bosco E. A Novel BRCA1-Associated Protein-1 Isoform Affects Response of Mesothelioma Cells to Drugs Impairing BRCA1-Mediated DNA Repair. J Thorac Oncol. 2017 Apr 4. pii: S1556-0864(17)30274-5.

Kresoja-Rakic J, Kapaklikaya E, Ziltener G, Dalcher D, Santoro R, Christensen BC, Johnson KC, Schwaller B, Weder W, Stahel RA, Felley-Bosco E. Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells. Oncotarget. 2016 Apr 19;7(16):21272-86.

Echeverry N, Ziltener G, Barbone D, Weder W, Stahel RA, Broaddus VC, Felley-Bosco E. Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors. Cell Death Dis. 2015 May 7;6:e1757.

Renganathan A, Kresoja-Rakic J, Echeverry N, Ziltener G, Vrugt B, Opitz I, Stahel RA, Felley-Bosco E. GAS5 long non-coding RNA in malignant pleural mesothelioma. Mol Cancer. 2014 May 23;13:119.

Shi Y, Moura U, Opitz I, Soltermann A, Rehrauer H, Thies S, Weder W, Stahel RA, Felley-Bosco E. Role of hedgehog signaling in malignant pleural mesothelioma. Clin Cancer Res. 2012 Sep 1;18(17):4646-56.

Funding

Swiss National Science Foundation, CTI, Stiftung für Angewandte Krebsforschung, Walter- Bruckerhoff Foundation, University of Zurich

Thoracic Surgery - Prof. Dr. med. Isabelle Schmitt-Opitz

Group Leader

Prof. Dr. med. Isabelle Schmitt-Opitz
schmitt_opitz_isabelle.jpg

Contact Information

Department of Thoracic Surgery
University Hospital Zurich
Raemistrasse 100
CH-8091 Zurich
+41 44 255 88 02
isabelle.schmitt-opitz@usz.ch

Group Members

Mayura Meerang, Postdoctoral research fellow
Michaela Kirschner, Postdoctoral research fellow
Vanessa Orlowski, lab technician
Olivia Lauk, resident surgeon
Kathrin Oehl, PhD Student
Martina Friess, data manager
Chloé Spichiger, research administration
Guillaume Wuilleret, doctoral student
Tadeusz Brunn, doctoral student
Max Lacour, doctoral student
Jessica Kreienbühl, doctoral student
Seraina Müller, master student
Gian-Marco Monsch, doctoral student
Ornella Crameri, master student
Lukas Funke, master student

Research focus

The research focus of the working group led by Prof. Dr. Isabelle Schmitt-Opitz is the improvement of malignant pleural mesothelioma treatment. In order to achieve this aim, various translational projects are conducted to.

One main focus of experimental research is the investigation of new therapeutic approaches using cell culture and small animal models of malignant pleural mesothelioma.Long-term work in this field formed the basis for clinical application of the chemotherapeutic agent cisplatin, bound to the endogenous adhesive fibrin, in the thoracic cavity (so-called intracavitary therapy) after surgical extraction of the tumor. After a decade of research in the laboratory, this combination is currently tested in a clinical phase II study (INFLuenCe-Meso).In further experimental studies, we now examine the possibility to use intracavitary chemotherapy to sensitize patients for a subsequent radiotherapy. This would allow the use of a lower radiation dose and thus this form of therapy would be available to a larger amount of patients. In a second project, we search for new medication for the treatment of mesothelioma. For this purpose we treat cells isolated from the tumor tissue (cultivated in petri dishes) with various new active substances and examine the effect on the cell growth. The investigated active substances are e.g. inhibitors of proteins and signal pathways, which are overexpressed in mesothelioma and most likely play an important role in the development and progression of mesothelioma.

The second focus is the identification of new molecular markers, which are traceable in the tumor tissue or blood of patients. We are interested in i) prognostic markers, allowing a general indication about the patients' prognosis, and ii) predictive markers able to predict the success of chemotherapy or other treatments. Predictive markers are especially important, as the information about the possible success or failure of a certain treatment method keeps the patient from unnecessary unsuccessful treatments and allows a personalized therapy concept for each individual patient. The examined molecular markers are proteins in the tumor tissue, microRNAs (small pieces of genetic information, which play an important role in the fine adjustment of signal pathways in the cells), and mutations in the genetic information, which lead to changes of the tumor cells characteristics. For these studies, we are working in close collaboration with Clinical Pathology.

Furthermore, Prof. Schmitt-Opitz is leading the study "Mesoscape 001 - pS6", initiated by the European Thoracic Oncology Platform (ETOP). Mesoscape is a Europe-wide central virtual tumour bank combined with a clinical database, which will allow participating centres (hospitals and universities) to examine a large amount of cases to find new biomarkers. The first project "Mesoscape 001 - pS6", is a validation of the possible new prognostic tumour marker pS6, which has been recently identified by Prof. Schmitt-Opitz's team.

Keywords

Malignant pleural mesothelioma (MPM), multimodal therapy, intraoperative therapy, biological markers

5 Selected Publications

Opitz I, Friess M, Kestenholz P, Schneiter D, Frauenfelder T, Nguyen-Kim DL, Seifert B, Hoda MA, Klepetko W, Stahel RA, Weder W. A new prognostic score supporting treatment allocation for multimodality therapy for malignant pleural mesothelioma- A review of 12 years' experience. J Thorac Oncol. 2015 Nov;10(11):1634-41

Bitanihirwe B, Meerang M, Friess M, Soltermann A, Frischknecht L, Thies S, Felley-Bosco E, Tsao M, Allo G, de Perrot M, Seifert B, Moch H, Stahel R, Weder W, Opitz I. PI3K/mTOR Signaling in Mesothelioma Patients Treated with Induction Chemotherapy Followed by Extrapleural Pneumonectomy. J Thorac Oncol. 2014 Feb;9(2):239-47

Frauenfelder T, Tutic M, Weder W, Götti RP, Stahel RA, Seifert B, Opitz I. Volumetry: an alternative to assess therapy response for malignant pleural mesothelioma? Eur Respir J. 2011 Jul;38(1):162-8

Opitz I, Erne B, Demirbas S, Jetter A, Seifert B, Stahel RA, Weder W. Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy for malignant pleural mesothelioma – a preclinical study. J Thorac Cardiovasc Surg. 2011 Jan;141(1):65-71

Opitz I, Soltermann A, Abaecherli M, Hinterberger M, Probst-Hensch N, Stahel R, Moch H, Weder W (2008) PTEN expression is a strong predictor of survival in mesothelioma patients. Eur J Cardiothorac Surg. Mar; 33(3): 502-6

Opitz I, Lardinois D, Arni S, Hillinger S, Vogt B, Odermatt B, Rousson V, Weder W. Local Recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment. Eur J Cardiothorac Surg. 2007 May; 31(5): 773-8

Funding

Swiss National Science Foundation, Swiss Cancer League, Lunge Zürich, Vontobel Foundation, Huggenberger Foundation, Matching Fund of University of Zurich, Becon Foundation, Polianthes Foundation, SAKF Foundation, SUVA

URL

http://www.thorax.usz.ch/forschung/Seiten/default.aspx


Institute of Diagnostic and Interventional Radiology

Institute of Diagnostic and Interventional Radiology - Prof. Dr. med. Jürg Hodler

Chairman

Prof. Dr. med. Jürg Hodler
Hodler_Juerg.png

Name of Institution

Institute of Diagnostic and Interventional Radiology
University Hospital Zurich & University of Zurich
Rämistr. 100
CH-8091 Zurich
+41 44 255 2900
juerg.hodler@usz.ch

In the Institute of Diagnostic and Interventional Radiology several independent research groups are organized in an organ/technique focused structure.


Research groups

CT Imaging: Prof. Dr. Hatem Alkadhi, MD, MPH, EBCR is heading the CT Imaging section, including the application of new innovative techniques such as dual-energy and perfusion CT for advanced, quantitative imaging of cancer.

Breast Imaging: The Breast Imaging research group of Prof. Dr. Andreas Boss is engaged with the development and application of new imaging methods for breast cancer detection including new magnetic-resonance imaging techniques, phase-contrast mammography and breast-CT.

Thoracic Imaging: The Thoracic Imaging Group (Prof. Dr. Thomas Frauenfelder) focuses on imaging of malignant mesothelioma and bronchial cancer, evaluating volumetry as an independent prognostic parameter and as a marker for the response of chemotherapy in cooperation with the Department of Surgery of the University Hospital Zurich.  Furthermore studies in the field of radiomics as biomarker in multi-modality treatment of locally advanced non-small cell lung cancer are running.

Abdominal Imaging: The focus of the research group lead by PD Cäcilia Reiner is to investigate hepato-pancreatico-biliary diseases with advanced imaging methods in magnetic resonance imaging and computed tomography with a special focus on hepatic tumor diagnosis and therapy response evaluation.

Prostate Imaging: (PD Dr. Olivio Donati) Research aimed at investigating the use of advanced and functional imaging modalities such as Diffusion-weighted and dynamic contrast-enhanced magnetic resonance Imaging (MRI) for the non-invasive diagnosis, staging, Treatment response assessment and follow-up of patients with prostate cancer.

Magnetic Resonance Physics: The research group of PD Dr. Cristina Rossi develops new MRI techniques including suitable post-processing methods aiming at the characterization and detection of cancer.

Machine Learning and Big data analysis group: (Hatem Alkadhi, Andreas Boss, Christoph Karlo) The research group aims to integrate research in the broad field of big data, texture analysis and machine learning.

Translational research: In the translational research group (Andreas Boss) small animal models are applied to obtain a better understanding of tumor pathophysiology. Techniques include small animal MRI, micro-CT and application of nanoparticles.

Keywords

Magnetic resonance imaging, computer-tomography, mammography, ultrasound, machine learning, translational research.

Selected Publications

Gordic S, Puippe GD, Krauss B, Klotz E, Desbiolles L, Lesurtel M, Müllhaupt B, Pfammatter T, Alkadhi H. Correlation between Dual-Energy and Perfusion CT in Patients with Hepatocellular Carcinoma. Radiology 2016 Jul;280(1):78-87.

Becker AS, Marcon M, Ghafoor S, Wurnig MC, Frauenfelder T, Boss A. Deep Learning in Mammography: Diagnostic Accuracy of a Multipurpose Image Analysis Software in the Detection of Breast Cancer. Invest Radiol. 2017 Jul;52(7):434-440.

Martini K, Meier A, Opitz I, Weder W, Veit-Haibach P, Stahel RA, Frauenfelder T. Diagnostic accuracy of sequential co-registered PET+MR in comparison to PET/CT in local thoracic staging of malignant pleural mesothelioma. Lung Cancer. 2016 Apr;94:40-5.

Reiner CS, Gordic S, Puippe G, Morsbach F, Wurnig M, Schaefer N, Veit-Haibach P, Pfammatter T, Alkadhi H. Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting Response to Transarterial Radioembolization: Value of Tumor Heterogeneity Assessment. Cardiovasc Intervent Radiol. 2016;39:400-408.

Barth BK, De Visschere PJ, Cornelius A, Nicolau C, Vargas HA, Eberli D, Donati OF. Detection of Clinically Significant Prostate Cancer: Short Dual-Pulse Sequence versus Standard Multiparametric MR Imaging-A Multireader Study. Radiology. 2017 Mar 27:162020. doi: 10.1148/radiol.2017162020. [Epub ahead of print]

Stieb S, Boss A, Wurnig MC, Özbay PS, Weiss T, Guckenberger M, Riesterer O, Rossi C. Non-parametric intravoxel incoherent motion analysis in patients with intracranial lesions: Test-retest reliability and correlation with arterial spin labeling. Neuroimage Clin. 2016 Jun 2;11:780-8.

Funding

Swiss National Science Foundation, Swiss Cancer League, University of Zurich (among other Clinical Research Priority Program Molecular Imaging Network Zurich).

URL

http://www.radiologie.usz.ch/forschung/Seiten/default.aspx


Institute of Pathology and Molecular Pathology

Laboratory of Molecular Tumor Pathology & Translational Cancer Research - Prof. Dr. med. Holger Moch / PD Dr. Peter Schraml

Group Leader

Prof. Dr. med. Holger Moch/ PD Dr. Peter Schraml
moch_holger.pngSchraml_P_2.jpg

Name of Institution

Laboratory of Molecular Tumor Pathology & Translational Cancer Research
Institute of Pathology and Molecular Pathology
University Hospital Zurich & University of Zurich
Schmelzbergstrasse 12
CH-8091 Zurich
+41 44 255 2500
holger.moch@usz.ch


Group Members

Silvia Angori, PhD student
Aashil Batavia, PhD student
Hella Bolck, PhD
Claudia Corro, PhD student
Raquel Herrador, Technician
Magdalena Lukamowicz-Rajska, PhD
Katharina Mühlbauer, Technician
Chantal Pauli, MD
Peter Schraml, Assistant Professor
Adriana von Teichman, Technician

Research focus

The work of our group is primarily focussing on the evaluation of the relationship between molecular aberrations and prognostic factors in renal cell cancer (RCC). As the prognosis of advanced renal cell carcinoma (RCC) is poor, the identification of molecular markers for early stages and recurrent tumors as well as predictive markers for treatment response is of utmost importance to improve prognosis of RCC patients. To this end, our research projects aim at i. characterizing rare RCC entities; ii. investigating genetic and morphologic intra-tumor heterogeneity; iii. identifying tumor cells with stem cell properties, and iv. questioning the role of lymphoid structures in RCC.

Keywords

Renal cell cancer, rare subtypes, intra-tumoral heterogeneity, cancer stem cells, lymphoid structures.

5 Selected Publications

Ruf M, Mittmann C, Nowicka AM, Hartmann A, Hermanns T, Poyet C, van den Broek M, Sulser T, Moch H, Schraml P. pVHL/HIF-regulated CD70 expression is associated with infiltration of CD27+ lymphocytes and increased serum levels of soluble CD27 in clear cell renal cell carcinoma. Clin Cancer Res. 2015; 21:889-898

Nowicka AM, Häuselmann I, Borsig L, Bolduan S, Schindler M, Schraml P, Heikenwalder M, Moch H. A novel pVHL-independent but NEMO-driven pathway in renal cancer promotes HIF stabilization. Oncogene. 2016; 35:3125-3138

Ruf M, Moch H, Schraml P. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma. Int J Cancer. 2016; 139:396-403

Lukamowicz-Rajska M, Mittmann C, Prummer M, Zhong Q, Bedke J, Hennenlotter J, Stenzl A, Mischo A, Bihr S, Schmidinger M, Vogl U, Blume I, Karlo C, Schraml P, Moch H. MiR-99b-5p expression and response to tyrosine kinase inhibitor treatment in clear cell renal cell carcinoma patients. Oncotarget. 2016; 7:78433-78447

Razafinjatovo CF, Stiehl D, Deininger E, Rechsteiner M, Moch H, Schraml P. VHL missense mutations in the p53 binding domain show different effects on p53 signaling and HIFα degradation in clear cell renal cell carcinoma. Oncotarget. 2017; 8:10199-10212

Funding

Swiss National Science Foundation, Swiss Cancer League, Cancer League Zurich, Commission for Technology and Innovation, University of Zurich, Canton Zurich, Private: Roche

URL

http://www.pathologie.usz.ch/Seiten/default.aspx

Tissue-Biobank USZ - Prof. Dr. med. Holger Moch / PD Dr. phil. Peter Schraml

Group Leader

Prof. Dr. med. Holger Moch / PD Dr. Peter Schraml
moch_holger.pngSchraml_P_2.jpg

Name of Institution

Tissue-Biobank USZ
Institute of Pathology and Molecular Pathology
University Hospital Zurich & University of Zurich
Schmelzbergstrasse 12
CH-8091 Zurich
+41 44 255 2500
peter.schraml@usz.ch

Group Members

Francesca Buja, Technician
Susanne Dettwiler, Senior Technician
Edward Fritz, Laboratory assistant
Raquel Herrador, Technician
Katharina Mühlbauer, Technician
Fabiola Prutek, Technician

Research focus

The University Hospital of Zurich has the mission to medicate the population in an optimal way. Medical research is essential to guarantee the permanent optimization of diagnostics, therapy and patient care in the future. Tissue samples that were surgically removed from patients for diagnostic and therapeutic reasons are an extremely important resource for studying diseases. The centralized Tissue-Biobank USZ collects, annotates and stores formalin fixed and native deep-frozen tissue samples for diagnostic enquiries, research projects as well as for clinical studies to meet the mission of the University Hospital. Tissue Microarrays (TMAs) with tissue cores from 20'000 patients have been generated and 4'500 immunohistochemically stained TMAs have been electronically archived. About 16'000 tissue samples from 11'000 patients are stored deep-frozen. In addition, a live cell-biobank for generating two- and three-dimensional cell culture systems deriving from native tissue of patients has also been established. The centralized Tissue-Biobank supports translational cancer research projects from the University Research Priority Program (URPP) and the Competence Center Personalized Medicine (CC-PM)

Keywords

Biobank, human tissue, primary cell cultures, general consent, human research law

5 Selected Publications

von Teichman A, Storz M, Dettwiler S, Moch H, Schraml P. Whole genome and transcriptome amplification: practicable tools for sustainable tissue biobanking? Virchows Arch. 2012; 461:571-580.

Schneider D, Riegman PH, Cronin M, Negrouk A, Moch H, Balling R, Penault-Llorca F, Zatloukal K, Horgan D. Accelerating the Development and Validation of New Value-Based Diagnostics by Leveraging Biobanks. Public Health Genomics. 2016; 19:160-169

Razafinjatovo C, Bihr S, Mischo A, Vogl U, Schmidinger M, Moch H, Schraml P. Characterization of VHL missense mutations in sporadic clear cell renal cell carcinoma: hotspots, affected binding domains, functional impact on pVHL and therapeutic relevance. BMC Cancer. 2016; 16:638

Beleut M, Soeldner R, Egorov M, Guenther R, Dehler S, Morys-Wortmann C, Moch H, Henco K, Schraml P. Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types. PLoS One. 2016; 11:e0161514

Cors JF, Kashyap A, Fomitcheva Khartchenko A, Schraml P, Kaigala GV. Tissue lithography: Microscale dewaxing to enable retrospective studies on formalin-fixed paraffin-embedded (FFPE) tissue sections. PLoS One. 2017; 12:e0176691

Funding

Swiss National Science Foundation (BioLink), University of Zurich, Hochspezialisierte Medizin Canton Zurich, Commission for Technology and Innovation, University Research Priority Programs

URL

http://www.pathologie.usz.ch/Seiten/default.aspx


University Children's Hospital, Department of Oncology

Department of Oncology, University Children's Hospital - Prof. Dr. med. Michael Grotzer

Group Leader

Prof. Dr. med. Michael Grotzer
Grotzer.png

Name of Institution

Department of Oncology
University Children's Hospital Zurich – Eleonore Foundation
Steinwiesstrasse 75
CH-8032 Zürich
+41 44 266 75 75 
michael.grotzer@kispi.uzh.ch 

Group Members

Martin Baumgartner, Ph.D., PD, Forschungsgruppenleiter
Anuja Neve, Ph.D.
Karthiga Santhana Kumar, Ph.D.
Dimitra Tripolitsioti, Ms.C.
Jessica Migliavacca, Ms.C.
Charles Capdeville, Ms.C.
Nicolas Gerber, MD

Research focus

Diffuse brain tissue infiltration in Medulloblastoma and other pediatric brain tumours poses a major therapeutic challenge in the clinic and contributes to mortality and high morbidity. Currently, no targeted therapies capable of reducing tissue infiltration are available and metastatic tumors are thus treated with aggressive treatment modalities. Our objective is to develop a therapeutic approach targeting cancer cell migration and invasion selectively. Towards that, we investigate the mechanisms driving and mediating brain tissue infiltration at the molecular and cellular level using in vitro and ex vivo approaches. We furthermore study the roles of the cellular and chemical tumor microenvironment in that process to explore alternative treatment strategies involving also the host environment.

Keywords

Medulloblastoma, brain tumor, cell migration and invasion, organotypic cerebellum culture, 3D cell culture, cancer cell signaling

5 Selected Publications

Anuja Neve1, Karthiga Santhana Kumar1, Dimitra Tripolitsioti1, Michael Grotzer1,2 and Martin Baumgartner. Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model. Scientific reports 2017, accepted for publication.

Karthiga Santhana Kumar, Max Pillong, Jens Kunze, Isabel Burghardt, Michael Weller, Michael A. Grotzer, Gisbert Schneider and Martin Baumgartner. Computer-assisted quantification of motile and invasive capabilities of cancer cells. Scientific reports 2015, 5:15338, DOI: 10.1038/srep15338

Karthiga Santhana Kumar, Dimitra Tripolitsioti, Min Ma, Jasmin Grählert, Katja B Egli, Giulio Fiaschetti, Tarek Shalaby1, Michael A Grotzer and Martin Baumgartner. The Ser/Thr kinase MAP4K4 drives c-Met-induced motility and invasiveness in a cell-based model of SHH medulloblastoma. SpringerPlus 2015 4:19 DOI 10.1186/s40064-015-0784-2

Fiaschetti G, Schroeder C, Castelletti D, Arcaro A, Westermann F, Baumgartner M, Shalaby T, Grotzer MA. NOTCH ligands JAG1 and JAG2 as critical pro-survival factors in childhood medulloblastoma. Acta Neuropathol Commun. 2014 Apr 7;2(1):39.

Fiaschetti G, Abela L, Nonoguchi N, Dubuc AM, Remke M, Boro A, Grunder E, Siler U, Ohgaki H, Taylor MD, Baumgartner M, Shalaby T, Grotzer MA. Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma. Br J Cancer. 2013 Dec 17. doi: 10.1038/bjc.2013.764

Funding

Swiss National Science Foundation, Swiss Cancer League, Childhood Cancer Research Foundation, Werner und Hedy Berger-Janser Foundation

URL

http://www.eicr.uzh.ch/de/Forschung/Onkologie/neurooncology.html

Department of Oncology, University Children's Hospital - Prof. Dr. sc. nat. Beat Schäfer

Group Leader

Prof. Dr. sc. nat. Beat Schäfer
Schaefer_Beat.jpg

Name of Institution

Department of Oncology
University Children's Hospital
Steinwiesstrasse 75
CH-8032 Zurich
+41 44 266 7553
beat.schaefer@kispi.uzh.ch

Group Members

Marco Wachtel, PhD, Senior Scientist
Eva Brack, MD/PhD student
Katharina Holste, PhD student
Dominik Laubscher, PhD student
Gabriele Manzella, PhD student
Joana Marques, PhD student
Johannes Ommer, PhD student
Gloria Pedot, PhD student
Michaela Römmele, Technician
Vadim Saratov, PhD student

Research focus

Despite multimodal treatment of surgery, radiotherapy and chemotherapy, the prognosis for children with metastatic sarcomas remains poor and has not improved over the last decades. Hence, we study molecular pathways that are deregulated in pediatric sarcoma using mainly rhabdomyosarcoma and Ewing sarcoma as models to introduce novel treatment options into clinical trials. We aim to improve our understanding of the biology of oncogenic fusion transcription factors on multiple levels including epigenetic regulation to target otherwise undruggable molecules. Since one of the big clinical problems is recurrent disease, we study mechanisms of drug resistance to improve re-sensitization, and also characterize sarcoma tumor propagating cells. Finally, to increase the number of new drugs potentially applicable for sarcoma treatment, we are building up a personalized drug profiling platform based on primary patient-derived xenograft models.

Keywords

Rhabdomyosarcoma, Ewing sarcoma, oncogenic transcription factors, epigenetics, tumor propagating cells, patient-derived xenografts, drug profiling.

5 Selected Publications

Thalhammer V, Lopez-Garcia LA, Herrero Martin D, Hecker R, Laubscher D, Gierisch ME, Wachtel M, Bode P, Nanni P, Blank B, Koscielniak E, Schäfer BW. PLK1 phosphorylates PAX3-FOXO1 the inhibition of which triggers regression of alveolar rhabdomyosarcoma. Cancer Res 2015, 75:98-110.

Giorgi C, Boro A, Rechfeld F, Lopez Garcia LA, Gierisch M, Schäfer BW, Niggli FK PI3K/AKT signaling modulates transcriptional expression of EWS/FLI1 through specificity protein 1, Oncotarget 2015, 6:28895-910.

Satheesha S, Manzella G, Bovay A, Casanova EA, Bode PK, Belle R, Feuchtgrube Sr, Jaaks P, Dogan N, Koscielniak E, and Schäfer BW. Targeting hedgehog signaling reduces self-renewal in Embryonal Rhabdomyosarcoma. Oncogene 2016, 35:2020-30.

Böhm M., Wachtel M., Marques J, Streiff N., Nanni P, Mamchaoui K, Santoro R, Schäfer BW Helicase CHD4 functions as epigenetic co-regulator of PAX3-FOXO1 activity in alveolar rhabdomyosarcoma. J Clin Invest 2016, 126:4237-4249.

Maria E. Gierisch, Franziska Pfistner, Laura A. Lopez-Garcia, Lena Harder, Beat W. Schäfer, Felix K. Niggli (2016). Proteasomal degradation of the EWS-FLI1 fusion protein is regulated by a single lysine residue, J Biol Chem 2016 291:26922-26933.

Funding

Swiss National Science Foundation, Childhood Cancer Research Foundation Switzerland, Swiss Cancer League, Cancer League Kt. Zürich, University of Zurich.

URL

https://www.kispi.uzh.ch/fzk/de/abteilungen/uebersicht/onkologie/Seiten/sarkome.aspx