Molecular Tumor Pathology and Translational Cancer Research
Our research aims at the identification and characterization of genes and pathways which may represent potential prognostic and predictive markers ('translational research') in human cancer. Genome and transcriptome analysis as well as the characterization of genetic alterations with their functional impacts in specific human tumors, primarily renal cell cancer, are of special interest.
Research Projects – Renal Cancer
Our research projects are performed in close collaboration with the Clinics of Urology and Oncology. Our main goals are to:
- functionally analyze cell surface glycoproteins for potential anti-tumor treatment;
- functionally analyze VHL mutations in RCC by focusing on their effects on pVHL binding partners;
- correlate VHL mutation types with patient prognosis and response to targeted therapies;
- identify VHL-independent molecular mechanisms in RCC using next generation sequencing;
- determine RCC tyrosine kinase inhibitor responders and non-responders based on microRNA profiles.
These projects are supported by the Swiss National Science Foundation, Oncosuisse, and the Krebsliga Zürich.
Research Projects – other Tumors
Additional translational cancer research projects are embedded in Life Science Programs matching major interests of research groups at the University Hospital Zurich (USZ), the University Zurich (UZH) and the Federal Institute of Technology (ETH).
The University Research Priority Programs (URPP) support bridges and research ties between the basic research carried out at the UZH and the clinical research at the USZ. With one of such programs a live cell biobank has been established for colorectal, lung, breast, pancreatic, oropharyngeal, renal cancer, and melanoma, in collaboration with the clinics of dermatology. The llink to clinical information will be instrumental for functional in vitro/in vivo studies.
One major breakthrough was reached with the establishment of the Roche Zurich Hub, a public-private partnership between USZ, UZH, ETH and Roche, with the Institute of Pathology as a leading institution. This program on personalized Medicine aims at the identification of biomarkers of resistance/response to chemotherapy combinations in triple-negative breast cancers.
In collaboration with the Roche Innovation Center Zurich the establishment of novel culture models derived from freshly-resected primary tumors will allow to test cancer immunotherapy agents and their combinations in an environment that preserves the morphological and histopathological features of primary tumors. This project will be instrumental for the selection of the most active drug candidates and their combinations for entry into the clinic.
- Pflüger, D., et al.
Identification of Molecular Tumor Markers in Renal Cell Carcinomas with TFE3 Protein Expression by RNA Sequencing.
Neoplasia 15, 1231-1240 (2013). - Wyler, L., et al.
Brain metastasis in renal cancer patients: metastatic pattern, tumour-associated macrophages and chemokine/chemoreceptor expression.
Br J Cancer in press (2013). - Vogetseder, A., et al.
alphav-Integrin isoform expression in primary human tumors and brain metastases.
Int J Cancer 133, 2362-2371 (2013). - Rechsteiner, M., et al.
KRAS, BRAF, and TP53 deep sequencing for colorectal carcinoma patient diagnostics.
J Mol Diagn 15, 299-311 (2013). - Pawlowski, R., et al.
Loss of PBRM1 expression is associated with renal cell carcinoma progression.
Int J Cancer 132, E11-17 (2013). - Kaufmann, M.R., Schraml, P., Hermanns, T., Wenger, R.H. & Camenisch, G.
Onconeuronal antigen Cdr2 correlates with HIF prolyl-4-hydroxylase PHD1 and worse prognosis in renal cell carcinoma.
Exp Mol Pathol 94, 453-457 (2013). - Dannenmann, S.R., et al.
Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma.
Cancer Immunology Research 1, 1-8 (2013). - Casagrande, S., et al.
The protein tyrosine phosphatase receptor type J is regulated by the pVHL-HIF axis in clear cell renal cell carcinoma.
J Pathol 229, 525-534 (2013). - Albers, J., et al.
Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice.
EMBO Mol Med 5, 949-964 (2013). - Gerstung, M., et al.
Reliable detection of subclonal single-nucleotide variants in tumour cell populations.
Nat Commun 3, 811 (2012). - Boysen, G., et al.
Identification and functional characterization of pVHL-dependent cell surface proteins in renal cell carcinoma.
Neoplasia 14, 535-546 (2012). - Beleut, M., et al.
Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome.
BMC Cancer 12, 310 (2012). - von Teichman, A., et al.
VHL mutations and dysregulation of pVHL- and PTEN-controlled pathways in multilocular cystic renal cell carcinoma.
Mod Pathol 24, 571-578 (2011). - Suwaki, N., et al.
A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma.
Sci Transl Med 3, 85ra47 (2011). - Rechsteiner, M.P., et al.
VHL gene mutations and their effects on hypoxia inducible factor HIFalpha: identification of potential driver and passenger mutations.
Cancer Res 71, 5500-5511 (2011). - Morra, L., et al.
Relevance of periostin splice variants in renal cell carcinoma.
Am J Pathol 179, 1513-1521 (2011). - Dahinden, C., et al.
Mining tissue microarray data to uncover combinations of biomarker expression patterns that improve intermediate staging and grading of clear cell renal cell cancer.
Clin Cancer Res 16, 88-98 (2010). - Thoma, C.R., et al.
VHL loss causes spindle misorientation and chromosome instability.
Nat Cell Biol 11, 994-1001 (2009). - Schraml, P., et al.
Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia.
Mod Pathol 22, 31-36 (2009). - Luu, V.D., et al.
Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell carcinoma.
Clin Cancer Res 15, 3297-3304 (2009). - Balamurugan, K., et al.
Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed in papillary renal cell carcinoma and leads to attenuated hypoxic response.
Oncogene 28, 3274-3285 (2009).
