Dr Kevin Mellert
Dr Carolin Seeling
Carola Holley
Theresa Luxenhofer
Eva Mantel
Luisa Haase
Elisabeth Schweiger
Sarah Bette
Antonia Miller
Jana Jöchle
Hannah Ernert
Juliane Nell
Focal points
Establishment and characterisation of cell lines for research into targeted therapeutic approaches
Chordomas
Chordomas are tumours of the spinal column that originate in cells of the dorsal chorda. In close collaboration with the Barth working group ( AG Barth) , previously unexplored aspects of this rare tumour disease are being investigated. The constant expansion of the small number of established chordoma cell lines makes a significant contribution to global research in this field. The focus is currently on comparative studies between chordomas of different localisation (clivus vs. sacral chordomas) and the establishment of cell culture models for tumour evolution. Only a few research groups worldwide have succeeded in establishing lines of these rare tumours, which makes us the focus of many current studies in this field of research.
Richter Transformation
3-8% of patients diagnosed with CLL develop diffuse large B-cell lymphomas (DLBCLs). This circumstance is described by the term Richter transformation (RT). The term Richter syndrome (RS) is used synonymously. PCR-based techniques can be used to distinguish whether an RT is clonally related to the underlying CLL or not. Clonally unrelated RTs behave similarly to de novo DLBCLs in terms of treatment response and progression. RTs based on a common progenitor with CLL show considerably more severe disease progression with only very short survival times after diagnosis. Using the world's first cell culture models for Richter syndrome and a small archive cohort, we are attempting to identify molecular differences between clonally related and clonally unrelated RTs and to develop targeted therapeutic approaches on this basis.
Protein transduction
The introduction of proteins into living cells and the translocation from uptake and utilisation organelles into the cytoplasm of the cells is summarised by the term protein transduction. By stimulating specific integrated reagents with visible light, it is possible to transfer proteins stored in endo- and lysosomes into the cytoplasm.
Range of methods
Cell culture
Cytogenetic techniques
Fluorescence in situ hybridisation
Chromosome painting
Immunohistochemistry/immunocytochemistry/proximity ligation assay
Molecular biological techniques (PCR, qPCR, Western blot, immunoprecipitation of proteins, sequence analyses)
Clonality analyses
Laser-based microdissection
Protein introduction into living cells
Live cell imaging
Umbaugh CS, Groth M, Erkut C, Lee KS, Marinho J, Linder S, Iser F, Kapp JN, Schroeter P, Dolaner S, Kayserili A, Helm D, Schneider M, Hartmann J, Walch P, Barth TFE, Mellert K, Dreier B, Schaefer JV, Plückthun A, Fröhling S, Scholl C. Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma. Sci Adv. 2025 Sep 5;11(36):eadu2796. doi: 10.1126/sciadv.adu2796. Epub 2025 Sep 3. PMID: 40901948; PMCID: PMC12407079.
Seeling C, Neumahr J, Häberle F, Lechel A, Möller P, Gaisa NT, Barth TFE, Mellert K. Cucurbitacin B Exhibits Antitumor Effects on Chordoma Cells via Disruption of Brachyury. Int J Mol Sci. 2025 Apr 18;26(8):3864. doi: 10.3390/ijms26083864. PMID: 40332566; PMCID: PMC12028342.
Omezzolli G, Iannello A, Vallone FE, Brandimarte L, Micillo M, Bertola N, Lavarello C, Grinovero N, Ferrero G, Mellert K, Möller P, Bruno S, Furman RR, Allan JN, Petretto A, Deaglio S, Ravera S, Vaisitti T. Complementary approaches define the metabolic features that accompany Richter syndrome transformation. Cell Mol Life Sci. 2025 Apr 9;82(1):152. doi: 10.1007/s00018-025-05670-4. PMID: 40204982; PMCID: PMC11982009.
Bette S, Haase L, Nell J, Grieser T, von Baer A, Schultheiss M, Marienfeld R, Möller P, Barth TFE, Mellert K. Impact of CDK Inhibitors on TBXT Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma. Diagnostics (Basel). 2024 May 16;14(10):1028. doi: 10.3390/diagnostics14101028. PMID: 38786326; PMCID: PMC11120607.
Rigo A, Vaisitti T, Laudanna C, Terrabuio E, Micillo M, Frusteri C, D'Ulivo B, Merigo F, Sbarbati A, Mellert K, Möeller P, Montresor A, Di Napoli A, Cirombella R, Butturini E, Massaia M, Constantin G, Vinante F, Deaglio S, Ferrarini I. Decreased apoptotic priming and loss of BCL-2 dependence are functional hallmarks of Richter's syndrome. Cell Death Dis. 2024 May 9;15(5):323. doi: 10.1038/s41419-024-06707-5. PMID: 38724507; PMCID: PMC11082225.
Tschavoll F, Lutteri G, Leinauer B, Mellert K, Möller P, Barth TFE. Der Riesenzelltumor des Knochens – ein Update [Giant cell tumor of bone-an update]. Pathologie (Heidelb). 2023 Dec;44(Suppl 3):215-219. German. doi: 10.1007/s00292-023-01271-9. Epub 2023 Nov 20. PMID: 37985483.
Arndt S, Hartmann W, Rókusz A, Leinauer B, von Baer A, Schultheiss M, Pablik J, Fritzsche H, Mogler C, Antal I, Baumhoer D, Mellert K, Möller P, Szendrői M, Jundt G, Barth TFE. Histomorphometric Analysis of 38 Giant Cell Tumors of Bone after Recurrence as Compared to Changes Following Denosumab Treatment. Cancers (Basel). 2023 Aug 24;15(17):4249. doi: 10.3390/cancers15174249. PMID: 37686526; PMCID: PMC10486357.
Hild V, Mellert K, Möller P, Barth TFE. Giant Cells of Various Lesions Are Characterised by Different Expression Patterns of HLA-Molecules and Molecules Involved in the Cell Cycle, Bone Metabolism, and Lineage Affiliation: An Immunohistochemical Study with a Review of the Literature. Cancers (Basel). 2023 Jul 21;15(14):3702. doi: 10.3390/cancers15143702. PMID: 37509363; PMCID: PMC10377796.
Seeling C, Mosca E, Mantel E, Möller P, Barth TFE, Mellert K. Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas. Cancers (Basel). 2023 Mar 26;15(7):1977. doi: 10.3390/cancers15071977. PMID: 37046638; PMCID: PMC10093147.
Beck A, Dietenberger H, Kunz SN, Mellert K, Möller P. Emergence of SARS- CoV-2 spike protein at the vaccination site. Immun Inflamm Dis. 2023 Mar;11(3):e827. doi: 10.1002/iid3.827. PMID: 36988249; PMCID: PMC10052447.
Seeling C, Möller P, Barth TFE, Mellert K. [The Role of the Transcription Factor Brachyury in Chordoma]. Osteologie 2023; 32: 68–76. Seitenanzahl: 5
Mellert K, Seeling C, Möller P, Barth TFE. Chordome – Ein Update [Chordoma- An update]. Pathologie (Heidelb). 2022 Aug;43(Suppl 1):50-55. German. doi: 10.1007/s00292-022-01118-9. Epub 2022 Sep 29. PMID: 36175666.
Giesche J, Mellert K, Geißler S, Arndt S, Seeling C, von Baer A, Schultheiss M, Marienfeld R, Möller P, Barth TF. Epigenetic lockdown of CDKN1A (p21) and CDKN2A (p16) characterises the neoplastic spindle cell component of giant cell tumours of bone. J Pathol. 2022 Aug;257(5):687-696. doi: 10.1002/path.5925. Epub 2022 Jun 7. PMID: 35522566.
Maier J, Lechel A, Marienfeld R, Barth TFE, Möller P, Mellert K. CARD9 Forms an Alternative CBM Complex in Richter Syndrome. Cancers (Basel). 2022 Jan 21;14(3):531. doi: 10.3390/cancers14030531. PMID: 35158799; PMCID: PMC8833648.
Seeling C, Lechel A, Svinarenko M, Möller P, Barth TFE, Mellert K. Molecular features and vulnerabilities of recurrent chordomas. J Exp Clin Cancer Res. 2021 Jul 30;40(1):244. doi: 10.1186/s13046-021-02037-y. PMID: 34330313; PMCID: PMC8325178.
Gull HH, Karadag C, Senger B, Sorg RV, Möller P, Mellert K, Steiger HJ, Hänggi D, Cornelius JF. Ciprofloxacin enhances phototoxicity of 5-aminolevulinic acid mediated photodynamic treatment for chordoma cell lines. Photodiagnosis Photodyn Ther. 2021 Sep;35:102346. doi: 10.1016/j.pdpdt.2021.102346. Epub 2021 May 24. PMID: 34038764.
Leinauer B, Wolf E, Werner M, Baumhoer D, Breining T, Luebke AM, Maas R, Schultheiß M, von Baer A, Sufi-Siavach A, Moritz C, Geißler S, Mellert K, Möller P, Barth TFE, Jundt G. H3F3A-mutated giant cell tumour of bone without giant cells-clinical presentation, radiology and histology of three cases. Histopathology. 2021 Nov;79(5):720-730. doi: 10.1111/his.14401. Epub 2021 Jul 21. PMID: 33991114.
Hasenfratz M, Mellert K, Marienfeld R, von Baer A, Schultheiss M, Roitman PD, Aponte-Tinao LA, Lehner B, Möller P, Mechtersheimer G, Barth TFE. Profiling of three H3F3A-mutated and denosumab-treated giant cell tumors of bone points to diverging pathways during progression and malignant transformation. Sci Rep. 2021 Mar 11;11(1):5709. doi: 10.1038/s41598-021-85319-x. PMID: 33707617; PMCID: PMC7952552.
Schmid T, Maier J, Martin M, Tasdogan A, Tausch E, Barth TFE, Stilgenbauer S, Bloehdorn J, Möller P, Mellert K. U-RT1 - A new model for Richter transformation. Neoplasia. 2021 Jan;23(1):140-148. doi: 10.1016/j.neo.2020.11.010. Epub 2020 Dec 11. PMID: 33316538; PMCID: PMC7736907.
Mellert K, Benckendorff J, Leithäuser F, Zimmermann K, Wiegand P, Frascaroli G, Buck M, Malaise M, Hartmann G, Barchet W, Fürst D, Mytilineos J, Mayer- Steinacker R, Viardot A, Möller P. U-DCS: characterization of the first permanent human dendritic sarcoma cell line. Sci Rep. 2020 Dec 4;10(1):21221. doi: 10.1038/s41598-020-77471-7. PMID: 33277516; PMCID: PMC7718904.
Fellermann M, Huchler C, Fechter L, Kolb T, Wondany F, Mayer D, Michaelis J, Stenger S, Mellert K, Möller P, Barth TFE, Fischer S, Barth H. Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells. Toxins (Basel). 2020 Sep 1;12(9):563. doi: 10.3390/toxins12090563. PMID: 32883045; PMCID: PMC7551598.
Mellert K, Martin M, Lennerz JK, Lüdeke M, Staiger AM, Kreuz M, Löffler M, Schmitz N, Trümper L, Feller AC, Hartmann S, Hansmann ML, Klapper W, Stein H, Rosenwald A, Ott G, Ziepert M, Möller P. The impact of SOCS1 mutations in diffuse large B-cell lymphoma. Br J Haematol. 2019 Dec;187(5):627-637. doi: 10.1111/bjh.16147. Epub 2019 Aug 12. PMID: 31407320; PMCID: PMC6899586.
Lübbehüsen C, Lüke J, Seeling C, Mellert K, Marienfeld R, von Baer A, Schultheiss M, Möller P, Barth TFE. Characterization of Three Novel H3F3A-mutated Giant Cell Tumor Cell Lines and Targeting of Their Wee1 Pathway. Sci Rep. 2019 Apr 23;9(1):6458. doi: 10.1038/s41598-019-42611-1. PMID: 31015476; PMCID: PMC6478864.
Böhm MJ, Marienfeld R, Jäger D, Mellert K, von Witzleben A, Brüderlein S, Wittau M, von Baer A, Schultheiss M, Mayer-Steinacker R, Rücker FG, Möller P, Bullinger L, Barth TFE. Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib. Sarcoma. 2019 Jan 21;2019:3914232. doi: 10.1155/2019/3914232. PMID: 30804704; PMCID: PMC6360577.
Giesche JP, von Baer A, Breining T, Marienfeld R, Mellert K, Lüke J, Schultheiss M, Möller P, Barth TFE. H3F3A-mutierter multifokaler Riesenzelltumor des Knochens : Eine äußerst seltene primär ossäre Erkrankung [H3F3A mutated multicentric giant cell tumor of bone : A very rare primary bone disease]. Pathologe. 2018 Sep;39(5):451-456. German. doi: 10.1007/s00292-018-0460-8. PMID: 30046846.
Mellert K, Lechner S, Lüdeke M, Lamla M, Möller P, Kemkemer R, Scheffzek K, Kaufmann D. Restoring functional neurofibromin by protein transduction. Sci Rep. 2018 Apr 18;8(1):6171. doi: 10.1038/s41598-018-24310-5. PMID: 29670214; PMCID: PMC5906691.
Jäger D, Lechel A, Tharehalli U, Seeling C, Möller P, Barth TFE, Mellert K. U-CH17P, -M and -S, a new cell culture system for tumor diversity and progression in chordoma. Int J Cancer. 2018 Apr 1;142(7):1369-1378. doi: 10.1002/ijc.31161. Epub 2017 Nov 27. PMID: 29148152.
Jäger D, Barth TFE, Brüderlein S, Scheuerle A, Rinner B, von Witzleben A, Lechel A, Meyer P, Mayer-Steinacker R, Baer AV, Schultheiss M, Wirtz CR, Möller P, Mellert K. HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral chordomas. Sci Rep. 2017 May 17;7(1):2032. doi: 10.1038/s41598-017-02174-5. PMID: 28515451; PMCID: PMC5435709.
Lüke J, von Baer A, Schreiber J, Lübbehüsen C, Breining T, Mellert K, Marienfeld R, Schultheiss M, Möller P, Barth TFE. H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant. Histopathology. 2017 Jul;71(1):125-133. doi: 10.1111/his.13190. Epub 2017 Apr 10. PMID: 28211081.
von Witzleben A, Goerttler LT, Marienfeld R, Barth H, Lechel A, Mellert K, Böhm M, Kornmann M, Mayer-Steinacker R, von Baer A, Schultheiss M, Flanagan AM, Möller P, Brüderlein S, Barth TF. Preclinical Characterization of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway. Cancer Res. 2015 Sep 15;75(18):3823-31. doi: 10.1158/0008-5472.CAN-14-3270. Epub 2015 Jul 16. PMID: 26183925.
Mellert K, Lamla M, Scheffzek K, Wittig R, Kaufmann D. Enhancing endosomal escape of transduced proteins by photochemical internalisation. PLoS One. 2012;7(12):e52473. doi: 10.1371/journal.pone.0052473. Epub 2012 Dec 21. PMID: 23285056; PMCID: PMC3528648.
Kaufmann D, Hoesch J, Su Y, Deeg L, Mellert K, Spatz JP, Kemkemer R. Partial Blindness to Submicron Topography in NF1 Haploinsufficient Cultured Fibroblasts Indicates a New Function of Neurofibromin in Regulation of Mechanosensoric. Mol Syndromol. 2012 Oct;3(4):169-79. doi: 10.1159/000342698. Epub 2012 Sep 27. PMID: 23239959; PMCID: PMC3507271.
Uhl M, Mellert K, Striegl B, Deibler M, Lamla M, Spatz JP, Kemkemer R, Kaufmann D. Cyclic stretch increases splicing noise rate in cultured human fibroblasts. BMC Res Notes. 2011 Oct 31;4:470. doi: 10.1186/1756-0500-4-470. PMID: 22040907; PMCID: PMC3220655.
Mellert K, Uhl M, Högel J, Lamla M, Kemkemer R, Kaufmann D. Aberrant Single Exon Skipping is not Altered by Age in Exons of NF1, RABAC1, AATF or PCGF2 in Human Blood Cells and Fibroblasts. Genes (Basel). 2011 Aug 2;2(3):562-77. doi: 10.3390/genes2030562. PMID: 24710210; PMCID: PMC3927615.