The Laboratory for Experimental Oncogenomics works on the establishment of assays to detect mutations and measure biomarkers in liquid biopsies of patients. Moreover, we analyze the function of potential oncogenes in tissue culture systems and in vivo tumor models.
1) GRP78 mediated resistance against chemotherapeutics
Therapy-resistant cancer cells translocate the endoplasmatic reticulum chaperone protein GRP78 on their cell membrane and release it upon stress conditions into the microenvironment. GRP78 activates pro-survival signaling on the cell surface of tumor cells (intrinsic resistance) and protects also via the microenvironment (extrinsic resistance) against anti-angiogenic drugs and finally attenuates immune responses to tumor cells. The present project aims to elucidate the underlying molecular mechanisms by the use of in vitro and in vivo tumor model systems.
2) EpCAM a biomarker for responses to cancer therapies
Epithelial tumor cells overexpress the antigen EpCAM on their cell membrane. Similar to NOTCH tumor cells and stem cells process EpCAM by membrane-associated proteases into a soluble extracellular part (EpEX) and a short intracellular signaling peptide (EpICD). EpICD acts as an enhancer of WNT-induced transcription of c-myc. In the present project we analyze the processing of EpCAM in samples of patients and measure the cleaved soluble EpEX in liquid biopsies by the use of an "in house" validated ELISA system.
3) Next Generation Sequencing (NGS) for stratification of cancer patients
In close collaboration with the Laboratory for Clinical Oncogenomics we work on the establishment of a novel diagnostic platform based on NGS technology. This Amplicon NGS approach aims to detect mutations in genes that are relevant for diagnostic and therapeutic decisions. The"Myeloid & Lymphoid Sequencing Panel" encompasses all know genomic mutations in hematological tumors that can be used to stratify patients for therapy decisions and responses. In a further step we plan to establish a "Driver Mutation Panel" on DNA isolated from liquid biopsies of solid tumors for detection of Minimal Residual Disease after chemotherapy and for detection of early stages of cancer.
Borjan B, Steiner N, Karbon S, Kern J, Francesch A, Hermann M, Willenbacher W, Gunsilius E, Untergasser G. BMC Cancer 2015, 15:738
Martowicz A, Seeber A, Untergasser G. Histol Histopathol 2016, 31(4):349-55
Seeber A, Braicu I, Untergasser G, Nassir M, Fong D, Botta L, Gastl G, Fiegl H, Zeimet A, Sehouli J, Spizzo G. Oncotarget 2015, 6(28):25017-23
Steiner N, Ribatti D, Willenbacher W, Jöhrer K, Kern J, Marinaccio C, Aracil M, García-Fernández LF, Gastl G, Untergasser G, Gunsilius E. Oncotarget 2015, 6(10):8200-9
Seeber A, Martowicz A, Spizzo G, Buratti T, Obrist P, Fong D, Gastl G, Untergasser G. BMC Cancer 2015, 15(1):372
Martowicz A, Kern J, Gunsilius E, Untergasser G. J Vis Exp 2015, May;(99):e52665
Thangavadivel S, Zelle-Rieser C, Olivier A, Postert B, Untergasser G, Kern J, Brunner A, Gunsilius E, Biedermann R, Hajek R, Pour L, Willenbacher W, Greil R, Jöhrer K. Oncotarget 2016, 7(48):78605-78618
Seeber A, Untergasser G, Spizzo G, Terracciano L, Lugli A, Kasal A, Kocher F, Steiner N, Mazzoleni G, Gastl G, Fong D. Int J Cancer 2016, 139(3):657-63
Schimke MM, Stigler R, Wu X, Waag T, Buschmann P, Kern J, Untergasser G, Rasse M, Steinmüller-Nethl D, Krueger A, Lepperdinger G. Nanomedicine 2016, (3):823-33
Pircher A, Jöhrer K, Kocher F, Steiner N, Graziadei I, Heidegger I, Pichler R, Leonhartsberger N, Kremser C, Kern J, Untergasser G, Gunsilius E, Hilbe W. Oncotarget 2016, 7(15):20109-23