ZMB Member Nicole Dünker

ZMB Member
Nicole Dünker

Next ZMB-Member
Nicole Dünker
© N.Dünker

Prof. Dr. Nicole Dünker

Institute of Anatomy II
University Hospital Essen
Hufelandstr. 55
45147 Essen

Research Overview

We are interested in factors influencing the etiology and progression of retinoblastoma (RB), the most common primary intraocular tumor in childhood. Untreated RB will grow and extend beyond the eye and undergo metastatic spread, commonly into regional lymph nodes, bone and CNS. Treatment of RB ranges from enucleation of the affected eye to eye salvage strategies including focal therapy (laser, cryotherapy), brachytherapy and/or chemotherapy. Chemotherapy can be applied systemically, commonly using an intra-arterial and/or intravitreal VEC (vincristine, etoposide and carboplatin) injection of chemotherapeutics. Chemotherapeutic treatment of RB is, however, limited not only by drug-related side effects, but also by developing drug resistances. Therefore, developing strategies to improve RB therapies for instance by sensitizing RB cells towards chemotherapeutics is a major challenge. Recent studies by our group suggest that trefoil factor family (TFF) peptides might be potential new candidates for supplementary therapeutic options for retinoblastoma along with common chemotherapy. Part of our research focuses on the up- and downstream molecules in the TFF signaling pathway as possible points of attack for future RB treatment. Another aspect of retinoblastoma, we are intensively investigating, are the mechanisms underlying chemoresistance, one of the major obstacles in retinoblastoma treatment. Most recently, we make use of nanoparticle-mediated substance delivery as well as nanoparticle-mediated gene knockdown and plan to also implement AAVs (adeno-associated viruses) as an applicable RB treatment strategy.

The chick in ovo chorioallantoic membrane (CAM) culture system serves to verify our in vitro data gained in human retinoblastoma cell lines in a semi in vivo system and we established a small CAM facility open for all researchers, who would like to implement this assay (see our homepage).

Research topics and methods

Molecular mechanisms of chemoresistances in retinoblastoma cell lines

-> new therapeutic strategies for treatment of chemoresistant retinoblastomas

  • in vitro analyses of chemoresistant retinoblastoma cell lines
  • in vivo analyses (in ovo CAM-assays; orthotopic rat model)

Role of Trefoil Factor Family (TFF) peptides in retinoblastoma etiology and progression

  • Expression of TFF peptides in the human retina, retinoblastoma cell lines and primary retinoblastoma tumors
  • Effects of TFF peptides on retinoblastoma cell tumor formation and metastasis
  • Significance of TFF peptides for migration and invasiveness of retinoblastoma cells (CAM assays)

Role of EMT (epithelial-mesenchymal transition) for retinoblastoma and chemoresistance development

  • expresssion analyses of epithelial and mesenchymal markers
  • overexpression and knockdown studies

Role of retinoic acid and BMP4 for apoptosis induction in retinoblastoma cells

  • Involvement of specific receptors and underlying signaling mechanisms
  • Expression studies (Real Time PCR / Western Blot)
  • Functional studies (cell culture/ DAPI-cell counts / apoptosis-arrays)
Read more

Selected Publications

    Journal articles

  • Apaolaza, Paola Stephanie; Busch, Maike; Asin-Prieto, Eduardo; Peynshaert, Karen; Rathod, R.; Remaut, Katrien; Dünker, Nicole; Göpferich, A.
    Hyaluronic acid coating of gold nanoparticles for intraocular drug delivery : Evaluation of the surface properties and effect on their distribution
    In: Experimental Eye Research Vol. 198 (2020) pp. 108151
    ISSN: 1096-0007; 0014-4835
  • Dünker, Nicole; Jendrossek, Verena
    Implementation of the chick chorioallantoic membrane (CAM) model in radiation biology and experimental radiation oncology research
    In: Cancers Vol. 11 (2019) Nr. 10, pp. 1499
    ISSN: 2072-6694
  • Busch, Maike; Klein, Stefan; Große-Kreul, Jan; Scheiner, Oliver; Metz, Klaus; Stephan, Harald; Dünker, Nicole
    p53, miR-34a and EMP1 : Newly Identified Targets of TFF3 Signaling in Y79 Retinoblastoma Cells
    In: International Journal of Molecular Sciences Vol. 20 (2019) Nr. 17, pp. 4129
    ISSN: 1422-0067
  • Busch, Maike; Papior, David; Stephan, Harald; Dünker, Nicole
    Characterization of etoposide- and cisplatin-chemoresistant retinoblastoma cell lines
    In: Oncology Reports Vol. 39 (2018) Nr. 1, pp. 160 - 172
    ISSN: 1791-2431; 1021-335X
  • Busch, Maike; Metz, Klaus; Beier, Manfred; Biewald, Eva; Dünker, Nicole
    Trefoil factor family 1 expression correlates with clinical outcome in petients withr retinoblastoma
    In: Retina Vol. 38 (2018) Nr. 12, pp. 2422 - 2428
    ISSN: 1539-2864
  • Busch, Maike; Große-Kreul, Jan; Wirtz, Janina Jasmin; Beier, Manfred; Stephan, Harald; Royer-Pokora, Brigitte; Metz, Klaus; Dünker, Nicole
    Reduction of the tumorigenic potential of human retinoblastoma cell lines by TFF1 overexpression involves p53/caspase signaling and miR-18a regulation
    In: International Journal of Cancer Vol. 141 (2017) Nr. 3, pp. 549 - 560
    ISSN: 0020-7136; 1097-0215
  • Große-Kreul, Jan; Busch, Maike; Winter, Claudia; Pikos, Stefanie; Stephan, Harald; Dünker, Nicole
    Forced Trefoil Factor Family Peptide 3 (TFF3) Expression Reduces Growth, Viability, and Tumorigenicity of Human Retinoblastoma Cell Lines
    In: PLoS ONE Vol. 11 (2016) Nr. 9, pp. 0163025
    ISSN: 1932-6203
  • Müller, Patrick; Doliva, Rebekka; Busch, Maike; Philippeit, Claudia; Stephan, Harald; Dünker, Nicole
    Additive effects of retinoic acid (RA) and bone morphogenetic protein 4 (BMP-4) apoptosis signaling in retinoblastoma cell lines
    In: PLoS ONE Vol. 10 (2015) Nr. 7,
    ISSN: 1932-6203
  • Busch, Maike; Philippeit, Claudia; Weise, Andreas; Dünker, Nicole
    Re-characterization of established human retinoblastoma cell lines
    In: Histochemistry and Cell Biology Vol. 143 (2015) Nr. 3, pp. 325 - 338
    ISSN: 0948-6143; 1432-119X; 0301-5564; 0018-2222; 0340-0239
  • Busch, Maik; Dünker, Nicole
    Trefoil factor family peptides : Friends or foes?
    In: Biomolecular concepts Vol. 6 (2015) Nr. 5-6, pp. 343 - 359
    ISSN: 1868-503X; 1868-5021
  • Philippeit, Claudia; Busch, Maike; Dünker, Nicole
    Epigenetic control of trefoil factor family (TFF) peptide expression in human retinoblastoma cell lines
    In: Cellular Physiology and Biochemistry Vol. 34 (2014) Nr. 3, pp. 1001 - 1014
    ISSN: 1015-8987; 1421-9778
  • Weise, Andreas; Dünker, Nicole
    High trefoil factor 1 (TFF1) expression in human retinoblastoma cells correlates with low growth kinetics, increased cyclin-dependent kinase (CDK) inhibitor levels and a selective down-regulation of CDK6
    In: Histochemistry and Cell Biology Vol. 139 (2013) Nr. 2, pp. 323 - 338
    ISSN: 0948-6143; 1432-119X
  • Paunel-Görgülü, Adnana-Nicoletta; Franke, Andreas G; Paulsen, Friedrich P; Dünker, Nicole
    Trefoil factor family peptide 2 acts pro-proliferative and pro-apoptotic in the murine retina.
    In: Histochemistry and Cell Biology Vol. 135 (2011) Nr. 5, pp. 461 - 473
    ISSN: 0948-6143; 1432-119X