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

  • Haase, André; Miroschnikov, Natalia; Klein, Stefan; Doege, Annika; Dünker, Nicole; Van Meenen, Dario; Junker, Andreas; Göpferich, Achim; Apaolaza, Paola Stephanie; Busch, Maike Anna
    New retinoblastoma (RB) drug delivery approaches : anti-tumor effect of atrial natriuretic peptide (ANP)-conjugated hyaluronic-acid-coated gold nanoparticles for intraocular treatment of chemoresistant RB
    In: Molecular Oncology (2024) in press
  • Xiang, Kexu; Kunin, Mikhail; Larafa, Safa; Busch, Maike; Dünker, Nicole; Jendrossek, Verena; Matschke, Johann
    α-Ketoglutarate supplementation and NAD+ modulation enhance metabolic rewiring and radiosensitization in SLC25A1 inhibited cancer cells
    In: Cell Death Discovery Vol. 10 (2024) Nr. 1, 27
  • Kerkhoff, Maximilian; Grunewald, Susanne; Schaefer, Christiane; Zöllner, Stefan K.; Plaumann, Pauline; Busch, Maike; Dünker, Nicole; Ketzer, Julia; Kersting, Josephine; Bauer, Sebastian; Hardes, Jendrik; Streitbürger, Arne; Dirksen, Uta; Hartmann, Wolfgang; Guder, Wiebke K.
    Evaluation of the Effect of Photodynamic Therapy on CAM-Grown Sarcomas
    In: Bioengineering Vol. 10 (2023) Nr. 4, 464
  • Chen, Zhen; Will, Rainer; Kim, Su Na; Busch, Maike Anna; Dünker, Nicole; Dammann, Philipp; Sure, Ulrich; Zhu, Yuan
    Novel Function of Cancer Stem Cell Marker ALDH1A3 in Glioblastoma : Pro-Angiogenesis through Paracrine PAI-1 and IL-8
    In: Cancers Vol. 15 (2023) Nr. 17, 4422
  • Busch, Maike; Haase, André; Alefeld, Emily; Biewald, Eva; Jabbarli, Leyla; Dünker, Nicole
    Trefoil Family Factor Peptide 1 : A New Biomarker in Liquid Biopsies of Retinoblastoma under Therapy
    In: Cancers Vol. 15 (2023) Nr. 19, 4828
  • Miroschnikov, Natalia; Dräger, Oliver; Van Meenen, Dario; Metz, Klaus; Budeus, Bettina; Dünker, Nicole; Busch, Maike
    Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma
    In: Journal of Oncology (2023) 2270097
  • Guder, Wiebke K.; Hartmann, Wolfgang; Buhles, Clarissa; Burdack, Maike; Busch, Maike; Dünker, Nicole; Hardes, Jendrik; Dirksen, Uta; Bauer, Sebastian; Streitbürger, Arne
    5-ALA-mediated fluorescence of musculoskeletal tumors in a chick chorio-allantoic membrane model : Preclinical in vivo qualification analysis as a fluorescence-guided surgery agent in Orthopedic Oncology
    In: Journal of Orthopaedic Surgery and Research Vol. 17 (2022) Nr. 1, 34
  • Van Meenen, Dario; Doege, Annika; Alefeld, Emily; Haase, André; Beier, Manfred; Kiefer, Tobias; Biewald, Eva; Metz, Klaus; Dräger, Oliver; Busch, Maike Anna; Dünker, Nicole
    ADAM10 and ADAM17 : Novel Players in Retinoblastoma Carcinogenesis
    In: International Journal of Molecular Sciences (IJMS) Vol. 23 (2022) Nr. 20, 12621
  • Doege, Annika; Steens, Rebecca; Dünker, Nicole; Busch, Maike Anna
    Retinoblastoma Cell Growth 'In Vitro' and Tumor Formation 'In Ovo' : Influence of Different Culture Conditions
    In: Methods and Protocols Vol. 5 (2022) Nr. 2, 21
  • Dräger, Oliver; Metz, Klaus; Busch, Maike; Dünker, Nicole
    Role of L1CAM in retinoblastoma tumorigenesis : identification of novel therapeutic targets
    In: Molecular Oncology Vol. 16 (2022) Nr. 4,
  • Busch, Maike; Haase, André; Miroschnikov, Natalia; Doege, Annika; Biewald, Eva; Bechrakis, Nikolaos E.; Beier, Manfred; Kanber, Deniz; Lohmann, Dietmar; Metz, Klaus; Dünker, Nicole
    TFF1 in Aqueous Humor : A Potential New Biomarker for Retinoblastoma
    In: Cancers Vol. 14 (2022) Nr. 3, 677
  • Busch, Maike; Miroschnikov, Natalia; Dankert, Jaroslaw Thomas; Wiesehöfer, Marc; Metz, Klaus; Stephan, Harald; Dünker, Nicole
    Impact of RARα and miR-138 on retinoblastoma etoposide resistance
    In: Tumor Biology Vol. 43 (2021) Nr. 1, pp. 11 - 26
  • 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) 108151
  • 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
  • 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 (IJMS) Vol. 20 (2019) Nr. 17, pp. 4129
  • 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
  • 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
  • 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
  • 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
  • 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,
  • 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
  • Busch, Maik; Dünker, Nicole
    Trefoil factor family peptides : Friends or foes?
    In: Biomolecular Concepts Vol. 6 (2015) Nr. 5-6, pp. 343 - 359
  • 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
  • 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
  • Gustmann, S.; Klein-Hitpaß, Ludger; Stephan, Harald; Weber, Susanne; Bornfeld, Norbert; Kaulisch, Marc; Lohmann, Dietmar; Dünker, Nicole
    Loss at chromosome arm 16q in retinoblastoma : confirmation of the association with diffuse vitreous seeding and refinement of the recurrently deleted region
    In: Genes, Chromosomes and Cancer Vol. 50 (2011) Nr. 5, pp. 327 - 337
  • 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
  • Haubold, Maike; Weise, Andreas; Stephan, Harald; Dünker, Nicole
    Bone morphogenetic protein 4 (BMP4) signaling in retinoblastoma cells
    In: International Journal of Biological Sciences Vol. 6 (2010) Nr. 7, pp. 700 - 715
  • Dohle, Daniel S.; Pasa, Susanne D.; Gustmann, Sebastian; Laub, Markus; Wissler, Josef H.; Jennissen, Herbert; Dünker, Nicole
    Chick ex ovo culture and ex ovo CAM assay : How it really works
    In: JoVE (2010) Nr. 33, pp. e1620
  • Gustmann, Sebastian; Dünker, Nicole
    In vivo-like Organotypic Murine Retinal Wholemount Culture
    In: JoVE (2010) Nr. 35, pp. e1634
  • Scheerer, N.; Dünker, Nicole; Imagawa, S.; Yamamoto, M.; Suzuki, N.; Fandrey, Joachim
    The anemia of the newborn induces erythropoietin expression in the developing mouse retina
    In: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology Vol. 299 (2010) Nr. 1, pp. R111 - R118
  • Pryce, Brian A.; Watson, Spencer S.; Murchison, Nicholas D.; Staverosky, Julia A.; Dünker, Nicole; Schweitzer, Ronen
    Recruitment and maintenance of tendon progenitors by TGFβ signaling are essential for tendon formation
    In: Development / Company of Biologists Vol. 136 (2009) Nr. 8, pp. 1351 - 1361
  • Beier, Marion; Franke, Andreas; Paunel-Görgülü, Adnana-Nicoletta; Scheerer, Nina; Dünker, Nicole
    Transforming growth factor beta mediates apoptosis in the ganglion cell layer during all programmed cell death periods of the developing murine retina
    In: Neuroscience Research Vol. 56 (2006) Nr. 2, pp. 193 - 203
  • Roussa, Eleni; Wiehle, Michael; Dünker, Nicole; Becker-Katins, Steffen; Oehlke, Oliver; Krieglstein, Kerstin
    Transforming growth factor β is required for differentiation of mouse mesencephalic progenitors into dopaminergic neurons in vitro and in vivo : Ectopic induction in dorsal mesencephalon
    In: Stem Cells Vol. 24 (2006) Nr. 9, pp. 2120 - 2129
  • Franke, Andreas G.; Gubbe, Christian; Beier, Marion; Dünker, Nicole
    Transforming growth factor-β and bone morphogenetic proteins: Cooperative players in chick and murine programmed retinal cell death
    In: The Journal of Comparative Neurology Vol. 495 (2006) Nr. 3, pp. 263 - 278
  • Dünker, Nicole; Valenciano, Ana Isabel; Franke, Andreas; Hernández-Sánchez, Catalina; Dressel, Ralf; Behrendt, Maik; De Pablo, Flora; Krieglstein, Kerstin; De La Rosa, Enrique J.
    Balance of pro-apoptotic transforming growth factor-β and anti-apoptotic insulin effects in the control of cell death in the postnatal mouse retina
    In: European Journal of Neuroscience Vol. 22 (2005) Nr. 1, pp. 28 - 38
  • Dünker, Nicole
    Transforming growth factor-β (TGF-β) and programmed cell death in the vertebrate retina
    In: International Review of Cytology Vol. 245 (2005) pp. 17 - 43
  • Rahhal, Belal; Dünker, Nicole; Comb, Stephanie; Krieglstein, Kerstin; Combs, Stephanie
    Isoform-specific role of transforming growth factor-β2 in the regulation of proliferation and differentiation of murine adrenal chromaffin cells in vivo
    In: Journal of Neuroscience Research Vol. 78 (2004) Nr. 4, pp. 493 - 498
  • Sculean, Anton; Junker, Rüdiger; Donos, Nikolaus; Windisch, Péter; Brecx, Michael; Dünker, Nicole
    Immunohistochemical evaluation of matrix molecules associated with wound healing following treatment with an enamel matrix protein derivative in humans
    In: Clinical Oral Investigations Vol. 7 (2003) Nr. 3, pp. 167 - 174
  • Dünker, Nicole; Krieglstein, Kerstin
    Reduced programmed cell death in the retina and defects in lens and cornea of Tgfβ2 –/– Tgfβ3 –/– double-deficient mice
    In: Cell and Tissue Research Vol. 313 (2003) Nr. 1, pp. 1 - 10
  • Farkas, Lilla M; Dünker, Nicole; Roussa, Eleni; Unsicker, Klaus; Krieglstein, Kerstin
    Transforming Growth Factor-βs Are Essential for the Development of Midbrain Dopaminergic NeuronsIn VitroandIn Vivo
    In: The Journal of Neuroscience Vol. 23 (2003) Nr. 12, pp. 5178 - 5186
  • Dünker, Nicole
    Transforming growth factor beta mediated programmed cell death in tissue regeneration of the murine intestinal mucosa.
    In: Annals of Anatomy Vol. 185 (2003) Nr. 4, pp. 299 - 300
  • Schuster, Norbert; Bender, Herdis; Rössler, Oliver G.; Philippi, Anja; Dünker, Nicole; Thiel, Gerald; Krieglstein, Kerstin
    Transforming growth factor-β and tumor necrosis factor-α cooperate to induce apoptosis in the oligodendroglial cell line OLI-neu
    In: Journal of Neuroscience Research Vol. 73 (2003) Nr. 3, pp. 324 - 333
  • Sculean, Anton; Junker, Rüdiger; Donos, Nikolaos; Berakdar, Mohammad; Brecx, Michael; Dünker, Nicole
    Immunohistochemical evaluation of matrix molecules associated with wound healing following regenerative periodontal treatment in monkeys
    In: Clinical Oral Investigations Vol. 6 (2002) Nr. 3, pp. 175 - 182
  • Dünker, Nicole; Schmitt, Kai; Krieglstein, Kerstin
    TGF-β is required for programmed cell death in interdigital webs of the developing mouse limb
    In: Mechanisms of Development Vol. 113 (2002) Nr. 2, pp. 111 - 120
  • Dünker, Nicole; Krieglstein, Kerstin
    Tgfβ2⁻/⁻Tgfβ3⁻/⁻ double knockout mice display severe midline fusion defects and early embryonic lethality
    In: Anatomy and Embryology Vol. 206 (2002) Nr. 1-2, pp. 73 - 83
  • Dünker, Nicole; Schmitt, Kai; Schuster, Norbert; Krieglstein, Kerstin
    The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa
    In: Gastroenterology Vol. 122 (2002) Nr. 5, pp. 1364 - 1375
  • Dünker, Nicole; Aumüller, Gerhard
    Transforming growth factor-beta 2 heterozygous mutant mice exhibit Cowper's gland hyperplasia and cystic dilations of the gland ducts (Cowper's syringoceles)
    In: Journal of Anatomy Vol. 201 (2002) Nr. 2, pp. 173 - 183
  • Schuster, Norbert; Dünker, Nicole; Krieglstein, Kerstin
    Transforming growth factor-β induced cell death in the developing chick retina is mediated via activation of c-jun N-terminal kinase and downregulation of the anti-apoptotic protein Bcl-XL
    In: Neuroscience Letters Vol. 330 (2002) Nr. 3, pp. 239 - 242
  • Dünker, Nicole; Schuster, Norbert; Krieglstein, Kerstin
    TGF-beta modulates programmed cell death in the retina of the developing chick embryo.
    In: Development Vol. 128 (2001) Nr. 11, pp. 1933 - 1942
  • Dünker, Nicole; Wake, Marvalee; Olson, Wendy M.
    Embryonic and larval development in the caecilian Ichthyophis kohtaoensis (Amphibia, gymnophiona) : a staging table
    In: Journal of morphology Vol. 243 (2000) Nr. 1, pp. 3 - 34
  • Krieglstein, Kerstin; Richter, Sandra; Farkas, Lilla; Schuster, Norbert; Dünker, Nicole; Oppenheim, Ronald W.; Unsicker, Klaus
    Reduction of endogenous transforming growth factors β prevents ontogenetic neuron death
    In: Nature Neuroscience Vol. 3 (2000) Nr. 11, pp. 1085 - 1090
  • Dünker, Nicole; Krieglstein, Kerstin
    Targeted mutations of transforming growth factor-β genes reveal important roles in mouse development and adult homeostasis
    In: EJB: the FEBS journal Vol. 267 (2000) Nr. 24, pp. 6982 - 6988
  • Dünker, Nicole
    Serotonergic neurons and processes in the adult and developing retina of Ichthyophis kohtaoensis (Amphibia; Gymnophiona)
    In: Anatomy and Embryology Vol. 199 (1999) Nr. 1, pp. 35 - 43
  • Dünker, Nicole
    A double-label analysis demonstrating the partial coexistence of tyrosine hydroxylase and GABA in retinal neurons of Ichthyophis kohtaoensis (Amphibia; Gymnophiona)
    In: Cell and Tissue Research Vol. 294 (1998) Nr. 2, pp. 387 - 390
  • Dünker, Nicole
    Colocalization of serotonin and GABA in retinal neurons of Ichthyophis kohtaoensis (amphibia; Gymnophiona)
    In: Anatomy and embryology Vol. 197 (1998) Nr. 1, pp. 69 - 75
  • Dünker, Nicole
    Development and organization of the retinal dopaminergic system of Ichthyophis kohtaoensis (Amphibia; Gymnophiona)
    In: Cell and Tissue Research Vol. 289 (1997) Nr. 2, pp. 265 - 274