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)