Urological research laboratory

Helmholtzstraße 10, D-89081 Ulm

Team

  • Profilbild von Prof. Dr. Cagatay Günes

    Prof. Dr. Cagatay Günes

    Leiter Forschungslabor

    Kontakt
    Kontakt
  • Profilbild von Dr. rer. nat. Anca Azoitei

    Dr. rer. nat. Anca Azoitei

  • Profilbild von Michaela Eggel (MTA)

    Michaela Eggel (MTA)

  • Profilbild von Iris Holzheu

    Iris Holzheu

  • Profilbild von Mingquan Chen

    Mingquan Chen

  • Profilbild von Qianyu Kang

    Qianyu Kang

  • Profilbild von Xue Kong

    Xue Kong

  • Profilbild von Junnan Liu

    Junnan Liu

  • Profilbild von Dr. med. Michael Melzer

    Dr. med. Michael Melzer

    Assistenzarzt, Junior Group Leader, Clinician Scientist

    Schwerpunkte

    Pluripotente Stammzellmodelle, Urothelkarzinomorganoide, Organkulturmodelle

    Kontakt
    Kontakt
  • Profilbild von Gregoire Najjar

    Gregoire Najjar

  • Profilbild von Xue Wang

    Xue Wang

  • Profilbild von Wang Wenya

    Wang Wenya

  • Profilbild von Cheng Zhang

    Cheng Zhang

  • Profilbild von Xi Zheng

    Xi Zheng

Projects/Research Topics

Fig. 1: Expression of ORP3 in the epithelial cells of the urinary bladder (left in vivo model, right human).
Fig. 1: Expression of ORP3 in the epithelial cells of the urinary bladder (left in vivo model, right human).

Molecular mechanisms of initiation, progression and invasion of bladder carcinoma

Urothelial carcinoma is one of the most common cancer diagnoses worldwide and tumours with pronounced chromosomal aberrations, so-called 'genomically unstable' carcinomas, are associated with a poor prognosis. In the development of specific urothelial driver mutations, the control of chromosome stability appears to have a significant tumour-biological and prognostic significance. In this study, the role of ploidy control genes, which were identified in genome-wide shRNA screens from the group's own preliminary work, will be investigated in vitro and in vivo. The project aims to investigate the influence of ploidy control genes (e.g. ORP3, Fig. 1) on the carcinogenesis of urothelial carcinoma and thus enable the development of innovative forms of therapy.

 

Research tumour cells
Fig. 2: Invasion of tumour cells into tissue in the organ culture model (pig bladder). Left: Pig bladder with epithelial layer (black arrow). Centre: de-epithelialised pig bladder. Right: de-epithelialised pig bladder after co-cultivation with invasive human tumour cells T24 (red arrow).

Metastasis of bladder cancer is the most common reason for the high mortality rate of this disease. Despite radical surgery at a clinically limited tumour stage (pT1 - pT3, pN0, R0), up to 50% of patients go on to develop metastases and usually die from the disease. Early tumour cell invasion and transmigration through natural barriers and cell layers (including the so-called basement membrane) play a key role in this process. In our experimental studies, we are working on the identification of molecular mechanisms of tumour cell invasion and metastasis using cell biological organ cultures (see Fig. 2) and other methods. The findings should make a decisive contribution to the development of new therapeutic approaches for the early phase of tumour cell spread in urothelial bladder carcinoma.

Telomerase and telomere biology

Telomeres
Fig. 3: The dual role of telomeres and telomerase in tumourigenesis. In the absence of telomerase, telomeres shorten in the course of life, which results in the activation of cellular protective mechanisms and functions as a kind of barrier against tumour development. However, in the absence of protective mechanisms, short, dysfunctional telomeres can lead to increased genetic instability and favour the development of tumours. The reactivation of telomerase is a key event in tumour development.

Telomeres, special protein-DNA complexes at the ends of chromosomes, have a key function in protecting the genetic material by suppressing the proliferation of cells with an incorrect number of chromosomes and inhibiting the development of tumours. A special enzyme, telomerase, is required for the replication of telomeres. Interestingly, in humans the activity of telomerase is suppressed during early embryonic development. With the exception of adult stem cells, telomerase activity is suppressed in most normal cells. However, this shortens the telomeres. One biological explanation for this is that tumour cells also require telomerase and therefore the suppression of telomerase activity during early embryonic development represents a protective mechanism against tumour development (Fig. 3).

The tumour cells of bladder cancer are almost all telomerase-positive, whereas normal urothelial tissue is telomerase-negative. Therefore, inhibition of telomerase activity in tumour tissue offers a potential therapeutic approach for patients with these tumours. Understanding the molecular mechanisms of telomerase reactivation in bladder cancer and the role of telomerase in tumour tissue is another focus of the urological research laboratory's scientific activities. This precise understanding is essential for the development of telomerase-based therapeutic approaches.

Patient-derived tumour organoids as a method of personalised therapy for bladder cancer

The use of organoids represents a new form of in vitro cultivation of cells. Here, cells are cultivated in a 3-dimensional scaffold of proteins that are intended to mimic the in vivo conditions of extracellular connective tissue. Under the right conditions, cells cultivated in this way form tiny tissue subunits consisting of a few and sometimes differently differentiated cells, so-called organoids. The 3D cell culture thus mimics the in vivo conditions in the body better than the usual 2D cell culture.

The new 3D cell culture techniques should make it possible to cultivate tumour cells from patient tumours. These organoids can then be determined in vitro in advance of a patient's drug therapy for the therapy response. On the one hand, this would allow the appropriate medication to be identified for the patient without wasting time with a potentially unsuitable first-line therapy. On the other hand, the patient would also be spared the possible side effects of unsuccessful therapy.

The Department of Urology at Ulm University Hospital offers the possibility of acquiring large numbers of patient samples through both minimally invasive and invasive open surgical procedures for bladder cancer. Tumour samples can also be obtained from early and advanced tumour stages. This means that almost the entire spectrum of bladder cancer is covered. If additional adjuvant therapy is required after surgery, comparisons of the effectiveness in vivo and in vitro can be made.

Publikationen

Wang X, Liu J, Azoitei A, Eiseler T, Meessen S, Jiang W, Zheng X, Makori AW, Eckstein M, Hartmann A, Stilgenbauer S, Elati M, Hohwieler M, Kleger A, John A, Zengerling F, Wezel F, Bolenz C, Günes C. Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics. Cell Mol Life Sci. 2023 Sep 22;80(10):299.

Melzer MK, Schirge S, Gout J, Arnold F, Srinivasan D, Burtscher I, Allgöwer C, Mulaw M, Zengerling F, Günes C, Lickert H, Christoffels VM, Liebau S, Wagner M, Seufferlein T, Bolenz C, Moon AM, Perkhofer L, Kleger A. TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration. BMC Biol. 2023 Mar 20;21(1):55.

Muranyi, Andrew; Ammer, Tobias; Kechter, Anna; Rawat, Vijay PS; Sinha, Amit; Gonzalez-Menendez, Irene; Quintanilla-Martinez, Leticia; Azoitei, Anca; Günes, Cagatay; Mupo, Annalisa; ,Npm1 haploinsufficiency in collaboration with MEIS1 is sufficient to induce AML in mice,Blood Advances,7,3,351-364,2023.

Cramer, Paul; Yonemura, Yoji; Behrendt, Laura; Marszalek, Aleksandra; Sannai, Mara; Durso, William; Guenes, Cagatay; Szafranski, Karol; Nakamura, Nobuhiro; Nasrashvili, Tornike; ,A YIPF5-GOT1A/B complex directs a transcription independent function of ATF6 in ER export. bioRxiv, 2023.12. 12.569033,2023.

Wang W, Zheng X, Azoitei A, John A, Zengerling F, Wezel F, Bolenz C, Günes C. The Role of TKS5 in Chromosome Stability and Bladder Cancer Progression. Int J Mol Sci. 2022 Nov 18;23(22):14283. doi: 10.3390/ijms232214283. PMID: 36430759; PMCID: PMC9698602.

Melzer MK, Breunig M, Lopatta P, Hohwieler M, Merz S, Azoitei A, Günes C, Bolenz C, Kleger A. Protocol to use de-epithelialized porcine urinary bladder as a tissue scaffold for propagation of pancreatic cells. STAR Protoc. 2022 Dec 16;3(4):101869.

Melzer MK, Zehe V, Zengerling F, Wezel F, Günes C, Maisch P, Bolenz C. Organoide als Meilenstein auf dem Weg zur personalisierten Therapie des Urothelkarzinoms: ein systematischer Review [Organoids as a milestone on the way to personalized treatment of urothelial carcinoma: a systematic review]. Urologie. 2022 Jul;61(7):745-752. German. doi: 10.1007/s00120-022-01854-z. Epub 2022 Jun 13. PMID: 35925247.

Meessen S, Najjar G, Azoitei A, Iben S, Bolenz C, Günes C. A Comparative Assessment of Replication Stress Markers in the Context of Telomerase. Cancers (Basel). 2022 Apr 28;14(9):2205. doi: 10.3390/cancers14092205. PMID: 35565334; PMCID: PMC9103842.

Muranyi A, Ammer T, Kechter A, Rawat VPS, Sinha A, Gonzalez-Menendez I, Quintanilla-Martinez L, Azoitei A, Günes C, Mupo A, Vassiliou G, Bamezai S, Buske C. Npm1 haploinsufficiency in collaboration with MEIS1 is sufficient to induce AML in mice. Blood Adv. 2023 Feb 14;7(3):351-364. doi: 10.1182/bloodadvances.2022007015. PMID: 35468619; PMCID: PMC9898611.

Melzer MK, Breunig M, Arnold F, Wezel F, Azoitei A, Roger E, Krüger J, Merkle J, Schütte L, Resheq Y, Hänle M, Zehe V, Zengerling F, Azoitei N, Klein L, Penz F, Singh SK, Seufferlein T, Hohwieler M, Bolenz C, Günes C, Gout J, Kleger A. Organoids at the PUB: The Porcine Urinary Bladder Serves as a Pancreatic Niche for Advanced Cancer Modeling. Adv Healthc Mater. 2022 Jun;11(11):e2102345. doi: 10.1002/adhm.202102345. Epub 2022 Feb 18. PMID: 35114730.                            

Zheng X, Wezel F, Azoitei A, Meessen S, Wang W, Najjar G, Wang X, Kraus J, Kestler H, John A, Zengerling F, Bolenz C and Günes C. Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma. Cancers. (Basel). 2021 July. Accepted

Walter K, Rodriguez-Aznar E, Ferreira MSV, Frappart PO, Dittrich T, Tiwary K, Meessen S, Lerma L, Daiss N, Schulte LA, Najafova Z, Arnold F, Usachov V, Azoitei N, Erkan M, Lechel A, Brümmendorf TH, Seufferlein T, Kleger A, Tabarés E, Günes CJohnsen SA, Beier F, Sainz B Jr, Hermann PC. Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells. Cancers (Basel). 2021 Jun 23;13(13):3145. doi: 10.3390/cancers13133145

Schneider L, Junnan L, Zhang C, Azoitei A, Meessen S, Zheng X, Cremer C, Gorzelanny C, Kempe-Gonzales S, Brunner C, Wezel F, Bolenz C, Gunes C*, John A. The Role of Interleukin-1 Receptor Antagonist in Bladder Cancer Cell Migration and Invasion. Int J Mol Sci. 2021. manuscript ID: ijms-1231167

Wezel F, Lustig J, Azoitei A, Liu J, Meessen S, Najjar G, Zehe V, Faustmann P, Zengerling F, John A, Martini T, Bolenz C, Günes C. Grainyhead-like 3 influences migration and invasion of urothelial carcinoma cells. Int J Mol Sci. 2021 Mar 15;22(6):2959.

Breunig et al. Modelling Plasticity and Dysplasia of Pancreatic Ductal Organoids Derived from Human Pluripotent Stem Cells. Manuscript Number: CELL-STEM-CELL-D-20-00326R3. Cell stem cell. 28, 1-20, 2021.

Diesinger T, Lautwein A, Bergler S, Buckert D, Renz C, Dvorsky R, Buko V, Kirko S, Schneider E, Kuchenbauer F, Kumar M, Günes C, Genze F, Büchele B, Simmet T, Haslbeck M, Masur K, Barth T, Müller-Enoch D, Wirth T, Haehner T. A New CYP2E1 Inhibitor, 12-Imidazolyl-1-dodecanol, Represents a Potential Treatment for Hepatocellular Carcinoma. Can J Gastroenterol Hepatol. 2021 Feb 2;2021:8854432.

John A, Günes C, Bolenz C, Vidal-Y-Sy S, Bauer AT, Schneider SW, Gorzelanny C. Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface. BMC Cancer. 2020 Dec 2;20(1):1178.

Xu P, Richter J, Blatz A, Gärtner F, Alberts R, Azoitei A, Makori WA, Meessen S, Knippschild U, Günes C. Downregulation of ORP3 Correlates with Reduced Survival of Colon Cancer Patients with Advanced Nodal Metastasis and of Female Patients with Grade 3 Colon Cancer. Int J Mol Sci. 2020 Aug 16;21(16):5894

Stroth L, Tharehalli U, Günes C, Lechel A. Telomeres and Telomerase in the Development of Liver Cancer Cancers (Basel). 2020 Jul 24;12(8):2048.

Meessen et al, Establishment of Real-Time Multispectral Imaging for the Detection of Bladder Cancer Using a Preclinical in Vivo Model. Bladder Cancer, 2020. 285-294

Diesinger T, Buko V, Lautwein A, Dvorsky R, Belonovskaya E, Lukivskaya O, Naruta E, Kirko S, Andreev V, Buckert D, Bergler S, Renz C, Schneider E, Kuchenbauer F, Kumar M, Günes C, Büchele B, Simmet T, Müller-Enoch D, Wirth T, Haehner T. Drug targeting CYP2E1 for the treatment of early-stage alcoholic steatohepatitis. PLoS One. 2020 Jul 23;15(7). doi: 10.1371/journal.pone.0235990.

Lang A, Whongsiri P, Yilmaz M, Lautwein T, Petzsch P, Greife A, Günes C, Köhrer K, Niegisch G, Hoffmann M, Schulz WA. Knockdown of UTX/KDM6A Enriches Precursor Cell Populations in Urothelial Cell Cultures and Cell Lines. Cancers (Basel). 2020 Apr 21;12(4). doi: 10.3390/cancers12041023.

John A, Robador JR, Vidal-Y-Sy S, Houdek P, Wladykowski E, Günes C, Bolenz C, Schneider SW, Bauer AT, Gorzelanny C. Urothelial carcinoma of the bladder induces endothelial cell activation and hypercoagulation. Mol Cancer Res.2020 Mar 31. doi: 10.1158/1541-7786.MCR-19-1041.

Njeru SN, Kraus J, Meena JK, Lechel A, Katz SF, Kumar M, Knippschild U, Azoitei A, Wezel F, Bolenz C, Leithäuser F, Gollowitzer A, Omrani O, Hoischen C, Koeberle A, Kestler HA*, Günes C*, Rudolph KL*. Aneuploidy-inducing gene knockdowns overlap with cancer mutations and identify Orp3 as a B-cell lymphoma suppressor. Oncogene. 2020 Feb;39(7):1445-1465. doi: 10.1038/s41388-019-1073-2. * Corresponding authors.

Kriegmair MC, Rohter J, Grychtol B, Theuring M, Ritter M, Günes C, Michel MS, Deliolanis NC, Bolenz C. Multiparametric Cystoscopy for Detection of Bladder Cancer Using Real-time Multispectral Imaging. Eur Urol. 2020 Feb;77(2):251-259. doi: 10.1016/j.eururo.2019.08. 024

S Meessen, S Iben, A Azoitei, S Wiese, C Bolenz, C Günes. Oncology Research and Treatment 2020. 43, 2-2

Morcos YAT, Najjar G, Meessen S, Witt B, Azoitei A, Kumar M, Wakileh G, Schwarz K, Schrezenmeier H, Zengerling F, Bolenz C, Günes C. A Novel Tissue and Stem Cell Specific TERF1 Splice Variant Is Downregulated in Tumour Cells. Int J Mol Sci. 2019 Dec 20;21(1). pii: E85. doi: 10.3390/ijms21010085.

Bolenz C, Rother J, Meessen S, Grychtol B, Majlesara A, Gharabaghi N, Günes C, Ritter M, Deliolanis N, Michel MS, Kriegmair MC. The development of real-time multispectral imaging for the diagnostics of bladder cancer.urologist A. 2019 Sep 17. doi: 10.1007/s00120-019-01037-3.

Günes C, Meessen S, Rother J, Kriegmair MC, Zheng X, Hernandez D, Grychtol B, Deliolanis N, Bolenz C. Development of a rodent model for preclinical evaluation of multiple contrast agents and real-time multispectral imaging in bladder cancer European Urology Supplements 18 (1), e1955

Eckstein M, Wirtz RM, Pfannstil C, Wach S, Stoehr R, Breyer J, Erlmeier F, Günes C, Nitschke K, Weichert W, Otto W, Keck B, Eidt S, Burger M, Taubert H, Wullich B, Bolenz C, Hartmann A, Erben P. A multicentre round robin test of PD-L1 expression assessment in urothelial bladder cancer by immunohistochemistry and RT-qPCR with emphasis on prognosis prediction after radical cystectomy Oncotarget. 2018 Feb 19;9(19):15001-15014.

Günes C, Wezel F, Southgate J, Bolenz C. Implications of TERT promoter mutations and telomerase activity for urothelial carcinogenesis. Nat Rev Urol. 2018 Jun;15(6):386-393.

Meena J, Kraus J, Lechel A, Kumar M, Muehlberger M, Andrulis M, Moeller P, Wezel F, Bolenz C, Kestler HA, Rudolph K-L, Günes C. Expression Profile of Novel Ploidy-Control Genes in Bladder Cancer. Oncology Research and Treatment 41, 73-74

Bolenz, C., Knauf, D., John, A., Erben, P., Steidler, A., Schneider, S.W. Günes, C., Gorzelanny, C. Decreased Invasion of Urothelial Carcinoma of the Bladder by Inhibition of Matrix-Metalloproteinase 7. Bladder Cancer, vol. 4, no. 1, pp. 67-75, 2018

Günes, C. Avila, A.I., Rudolph, K.L. Telomeres in Cancer. Differentiation. 2017 Dec 21;99:41-50.

Kumar, M., Lechel, A., Günes C. Telomerase: The Devil Inside. Genes 7 (8), 2016 Jul 29;7(8).

Cindric Vranesic A., Reiche J., Hoischen C., Wohlmann A., Bratsch J., Friedrich K., Günes B., Cappallo-Obermann H., Kirchhoff C., Diekmann S., Günes C., Huber O. Characterisation of SKAP/kinastrin isoforms: the N-terminus defines tissue specificity and Pontin binding. Hum Mol Genet. 2016 May 11.

Meena, J.K., Rudolph, K.L., Günes, C. Telomere Dysfunction, Chromosomal Instability and Cancer. Recent Results Cancer Res. 2015;200:61-79.

Meena, J.K., Cerutti, A., , Beichler, C., Morita, Y., Bruhn, C., Kumar, K., Kraus, J., Speicher, M.R., Wang, Z.-Q., Kestler, H.A., d'Adda di Fagagna, F., Günes, C.* and Rudolph, K.L.* Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion. EMBO J. 2015 May 12;34(10):1371-84.

* Corresponding authors.

Iben, S. and Günes, C. Telomerase exerts physiological and tumour promoting functions by stimulating ribosomal biogenesis. Telomerase and Telomeres. (2014) 1(1).

Gonzalez, O.G., Assfalg, R., Koch, S., Schelling, A., Meena, J.K., Kraus, J., Lechel, A., Katz, S-F., Benes, V., Scharffetter-Kochanek, K., Kestler, H.A., Günes, C.* and Iben, S*. Telomerase stimulates ribosomal DNA transcription in hyperproliferative conditions. Nature Communications. (2014) 5:4599.

* Corresponding authors.

Missios, P., Zhou, Y., Guachalla, LM., von Figura, G., Chakkarappan, SR., Binz, T., Gompf, A., Hartleben, G., Lellek, V., Günes, C., Sattler, RW., Song, Z., Illig, T., Klaus, S., Böhm, B., Wenz, T., Hiller, K. and Rudolph, KL. Glucose substitution prolongs lifespan of telomere dysfunctional mice by stimulating glycolysis and IGF-1 dependent mitochondrial biogenesis and oxidative glucose metabolism. Nature Communications. (2014) 5:4924.

Mesbah-Namin, S.A. and Gunes, C. Analysis of expression levels of E2F transcription factors in lineage negative hematopoietic stem cells of young and old mice. Molecular and Biochemical Diagnosis. (2014) 1:35-40, 2014.

Günes, C., Rudolph K.L. The role of telomeres in stem cells and cancer. Cell. (2013)152(3):390-3.

Kumar, M., Witt B., Knippschild, U., Koch, S., Meena, J.K., Heinlein, C., Weise, J.M., Krepulat, F., Kuchenbauer, F., Iben, S., Rudoplh, K.L., Deppert, W. and Günes, C. CEBP factors regulate TERT promoter activity in WAP-T mice during mammary carcinogenesis. Int J Cancer.(2013)132(9):2032-43.

Günes C., Rudolph, K.L. Telomere dysfunction puts the brakes on oncogene-induced cancers. EMBO J. (2012) 31(13):2833-4.

Hirner, H., Günes, CWollf, S., Bischof, J., Grothey, A., Oswald, F., Giamas, G., Blatz, A., Wegwitz, F., Bösl, M., Henne-Bruns, D., Leithäuser, F., Deppert, W., and Uwe Knippschild. Impaired CK1 delta activity attenuates SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo. PLoS One. (2012) 7(1).

Brassat, U., Balabanov, S., Bali, D., Dierlamm, J., Braig, M., Hartmann, U., Sirma, H.,Günes, CWege, H., Fehse, B., Gontarewicz, A., Dikomey, E., Borgmann, K., Brümmendorf, T-H. Functional p53 is required for effective telomerase inhibition in BCR-ABL-positive CML cells. Exp Hematol. (2011) 39(1):66-76.

Hartmann, D., Srivastava, U., Thaler, M., Kleinhans, K., Bauer, K., Kratzer, R.,Scheffold, A., Kloos, N., Katz, S.F., Song, Z., Begus-Nahrmann, Y., Kleger, A., von Figura, G., Lechel, A., Günes, CN'Kontchou, G., Brecht, M., Potthoff, A., Deterding, K., Wedemeyer, H.H., Ju, Z., Song, G., Xiao, F., Gillen, S., Schrezenmeier, H., Mertens, T., Friess, T., Blöcker, H., Manns, M.P., Beaugrand, M., and Rudolph, K.L. Telomerase gene mutations are associated with cirrhosis formation. Hepatology. (2011) 53:1608-1617.

Sirma, H., Kumar, M., Meena, K.J., Witt B., Weise, J. M., Lechel, A., Ande, S., Sakk, V., Guillouzu, C., Zender, L., Rudolph, K.-L. and Günes, C. The Promoter of Human Telomerase Reverse Transcriptase is activated during Liver Regeneration and Hepatocyte Proliferation. Gastroenterology. (2011) 141(1):326-337.

Schriefer, P., Günes, CWege, H. Rapid Quantification of Telomerase Activity Employing an Improved Real-time Telomeric Repeat Amplification Protocol in Clinical Tissue Samples Eliminates Interference by PCR Inhibitors. Journal of Cancer Science & Therapy. (2011) 3(8):176-180.

Bagis, H., Aktoprakligil, D., Günes, CAkkoc, T., Cetinkaya, G., Kankavi, O., Taskin, A-C, Arslan, K., Arat, S., Sekmen, S. Turgut, G., Tas, A., Dundar, M., Tsoncheva, V-L., Ivanov, I-G. Expression of Biologically Active Human Interferon Gamma Gene in the Milk of Transgenic Mice. Biochem Genet. (2011) 49(3-4):251-7.

Weise, J. M. and Günes, Ç. "Differential Regulation of Human and Mouse Telomerase Reverse Transcriptase Gene Promoter Activity during Testis Development". Mol Reprod Dev (2009) 76(3): 309-17.

Zafrakas, M., Tarlatzis, B., Streichert, T., Pournaropoulos, F., Wölfle, U., Wittek, B., Grimbizis, G., Papadimas, J., Pantel, K., Bontis, J. and Günes, Ç.Genome-wide microarray expression, absence of telomerase activity and array-CGH analysis in advanced ovarian endometriosis suggest high degree of differentiation rather than malignant potential. Int J Mol Med (2008) 21(3):335-44.

Ritz, J.M., andGünes, Ç.Telomeres and telomerase: A survey about methods and recent advances in cancer diagnosis and therapy. Histol Histopathol. (2006) 21: 1249-1261.

Ritz, J.M., Kühle, O., Riethdorf, S., Sipos, B., Deppert, W. Englert, C., and Günes, Ç. A Novel Transgenic Mouse Model Reveals Humanlike Regulation of an 8-kbp Human TERT Gene Promoter Fragment in Normal and Tumour Tissues. Cancer Res. (2005) 65(4), 1187-1196.

Zhang, B., Georgiev, O., Hagmann, M., Günes, ÇCramer, M., Faller, P., Vasak, M. and Schaffner, W. Activity of metal-responsive transcription factor 1 by toxic heavy metals and H2O2 in vitro is modulated by metallothionein. Mol Cell Biol (2003) 23(23):8471-85.

Günes, ÇLichtsteiner, S., Vasserot, A. P. and Englert, C. Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Mad1. Cancer Res. (2000) 60, 2116-2121.

Auf der Maur A., Belser, T., Wang, Y., Günes, ÇLichtlen, P., Georgiev, O. and Schaffner, W. Characterisation of the mouse gene for the heavy metal-responsive transcription factor MTF-1". Cell Stress and Chaperones. (2000) 5 (3), 196-206.

Günes, ÇHeuchel, R., Georgiev, O., Müller, K-H., Marino, S., Bluthmann, H., Aguzzi, A. and Schaffner, W.: "Embryonic lethality and liver degeneration in mice lacking the metal responsive transcriptional activator MTF-1. EMBO J. (1998) 17(10): 2846-2854.

Günes, Ç. and Müller-Hill, B.: Mutants in position 69 of Trp repressor of Escherichia coli K-12 with altered DNA-binding specificities. Mol. Gen. Genet. (1996) 251: 338-346.

Günes, ÇStaacke, D., von Wilcken-Bergmann, B. and Müller-Hill, B.: Cooperative binding of two Trp repressor dimers to alpha or beta centreed trp operators. Mol. Microbiol. (1996) 20(2) 375-384.

Günes, ÇStaacke, D., von Wilcken-Bergmann, B. and Müller-Hill, B.: The possible roles of residues 79 and 80 of Trp repressor from Escherichia coli K-12 in trp operator recognition. Mol. Gen. Genet. (1995) 246: 180-195.

Co-operations/memberships

  • Bladder Cancer Research Initiative for Drug Targets Germany (BRIDGE) Consortium e.V.
  • German Research Association for Bladder Cancer (DFBK e.V.)
  • German Association for Aging Research (DGfA)
  • German Testicular Tumour Study Group (GTCSG)
  • German Society of Residents in Urology (GeSRU) Academics
  • UroEvidence
  • Prof Lotan, Dr Krabbe, Department of Urology, UT Southwestern Medical Center, Dallas, Texas, USA
  • Prof Jennifer Southgate, Jack Birch Unit of Molecular Carcinogenesis, University of York, UK
  • PD Dr Wittenberg, T. Bergen Fraunhofer Institute for Integrated Circuits IIS, Erlangen, Germany
  • Dr Deliolanis, Fraunhofer IPA Project Group for Automation in Medicine and Biotechnology (PAMB), Mannheim
  • Prof Schneider, Dr Gorzelanny, Department of Experimental Dermatology, University Medicine Mannheim, Faculty of Medicine, Heidelberg University
  • Prof Michel, Prof Ritter, Prof Dr Erben. Dr Kriegmair, Department of Urology, Mannheim University Medical Centre, Faculty of Medicine, Heidelberg University
  • Prof. Dr Hans A. Kestler, Institute for Medical Systems Biology, Ulm.
  • Prof Dr Uwe Knippschild, Clinic for General and Visceral Surgery, Ulm
  • Prof Dr Karl-Lenhard Rudolph, Fritz Lipmann Institute for Ageing Research, Jena
  • Prof Dr Wolfgang A. Schulz, Dr Michele Hofmann, Clinic for Urology, Düsseldorf
  • Prof. Michael Höpfner, Institute of Physiology, Charité Universitätsmedizin Berlin, Molecular Tumour Therapy Research Group
  • Prof Dr Alexander Kleger, Clinic for Internal Medicine (Gastroenterology), Ulm
  • Prof. Dr Arndt Hartmann, Dr Markus Eckstein, Pathology, Erlangen University Hospital

 

Patents

  • Specific inhibitors of protein p21 as therapeutic agents
    C Günes, EM Hoffman, KL Rudolph
    US Patent App. 14/427,444

Sponsors

  • German Cancer Aid e.V.
  • German Research Foundation
  • Erich and Gertrud Roggenbuck Foundation
  • Dieter Platt Award for Experimental Gerontology
  • Wilhelm Sander Foundation
  • Else Kröner-Fresenius Foundation