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
H3F3A-mutated Giant Cell Tumour of Bone without Giant Cells - Clinical Presentation, Radiology, and Histology of Three Cases. 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. Histopathology. 2021 May 15. doi: 10.1111/his.14401. Online ahead of print. PMID: 33991114
Chordoma cell culture models: tumour heterogeneity in vitro.Mellert K. Osteology 2021; 30(01): 105 DOI: 10.1055/a-1341-5025.
Profiling of three H3F3A-mutated and denosumab-treated giant cell tumours of bone points to diverging pathways during progression and malignant transformation. Hasenfratz M, Mellert K, Marienfeld R, von Baer A, Schultheiss M, Roitman PD, Aponte-Tinao LA, Lehner B, Möller P, Mechtersheimer G, Barth TFE. Sci Rep. 2021 Mar 11;11(1):5709. doi: 10.1038/s41598-021-85319-x. PMID: 33707617 Free PMC article.
U-RT1 - A new model for Richter transformation. Schmid T, Maier J, Martin M, Tasdogan A, Tausch E, Barth TFE, Stilgenbauer S, Bloehdorn J, Möller P, Mellert K. Neoplasia. 2021 Jan;23(1):140-148. doi: 10.1016/j.neo.2020.11.010. Epub 2020 Dec 11. PMID: 33316538 Free PMC article.
U-DCS: characterisation of the first permanent human dendritic sarcoma cell line.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. Sci Rep. 2020 Dec 4;10(1):21221. doi: 10.1038/s41598-020-77471-7. PMID: 33277516 Free PMC article.
Sarcoma treatment in the era of molecular medicine. Grünewald TG, Alonso M, Avnet S, Banito A, Burdach S, Cidre-Aranaz F, Di Pompo G, Distel M, Dorado-Garcia H, Garcia-Castro J, González-González L, Grigoriadis AE, Kasan M, Koelsche C, Krumbholz M, Lecanda F, Lemma S, Longo DL, Madrigal-Esquivel C, Morales-Molina Á, Musa J, Ohmura S, Ory B, Pereira-Silva M, Perut F, Rodriguez R, Seeling C, Al Shaaili N, Shaabani S, Shiavone K, Sinha S, Tomazou EM, Trautmann M, Vela M, Versleijen-Jonkers YM, Visgauss J, Zalacain M, Schober SJ, Lissat A, English WR, Baldini N, Heymann D. EMBO Mol Med. 2020 Nov 6;12(11):e11131. doi: 10.15252/emmm.201911131. Epub 2020 Oct 13. PMID: 33047515
Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells. 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. Toxins (Basel). 2020 Sep 1;12(9):563. doi: 10.3390/toxins12090563. PMID: 32883045 Free PMC article.
The impact of SOCS1 mutations in diffuse large B-cell lymphoma.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. Br J Haematol. 2019 Dec;187(5):627-637. doi: 10.1111/bjh.16147. Epub 2019 Aug 12. PMID: 31407320 Free PMC article. Clinical Trial.
Characterization of Three Novel H3F3A-mutated Giant Cell Tumor Cell Lines and Targeting of Their Wee1 Pathway. Lübbehüsen C, Lüke J, Seeling C, Mellert K, Marienfeld R, von Baer A, Schultheiss M, Möller P, Barth TFE. Sci Rep. 2019 Apr 23;9(1):6458. doi: 10.1038/s41598-019-42611-1. PMID: 31015476 Free PMC article.
Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib. 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. Sarcoma. 2019 Jan 21;2019:3914232. doi: 10.1155/2019/3914232. eCollection 2019. PMID: 30804704 Free PMC article.
H3F3A mutated multicentric giant cell tumour of bone : A very rare primary bone disease. Giesche JP, von Baer A, Breining T, Marienfeld R, Mellert K, Lüke J, Schultheiss M, Möller P, Barth TFE. Pathologe. 2018 Sep;39(5):451-456. doi: 10.1007/s00292-018-0460-8. PMID: 30046846 German.
Restoring functional neurofibromin by protein transduction.Mellert K, Lechner S, Lüdeke M, Lamla M, Möller P, Kemkemer R, Scheffzek K, Kaufmann D. Sci Rep. 2018 Apr 18;8(1):6171. doi: 10.1038/s41598-018-24310-5. PMID: 29670214 Free PMC article.
U-CH17P, -M and -S, a new cell culture system for tumour diversity and progression in chordoma. Jäger D, Lechel A, Tharehalli U, Seeling C, Möller P, Barth TFE, Mellert K. Int J Cancer. 2018 Apr 1;142(7):1369-1378. doi: 10.1002/ijc.31161. Epub 2017 Nov 27. PMID: 29148152 Free article.
HOXA7, HOXA9, and HOXA10 are differentially expressed in clival and sacral chordomas. 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. Sci Rep. 2017 May 17;7(1):2032. doi: 10.1038/s41598-017-02174-5. PMID: 28515451 Free PMC article.
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. Lüke J, von Baer A, Schreiber J, Lübbehüsen C, Breining T, Mellert K, Marienfeld R, Schultheiss M, Möller P, Barth TFE. Histopathology. 2017 Jul;71(1):125-133. doi: 10.1111/his.13190. Epub 2017 Apr 10. PMID: 28211081
Preclinical Characterisation of Novel Chordoma Cell Systems and Their Targeting by Pharmocological Inhibitors of the CDK4/6 Cell-Cycle Pathway. 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. Cancer Res. 2015 Sep 15;75(18):3823-31. doi: 10.1158/0008-5472.CAN-14-3270. Epub 2015 Jul 16. PMID: 26183925 Free article.
Enhancing endosomal escape of transduced proteins by photochemical internalisation. Mellert K, Lamla M, Scheffzek K, Wittig R, Kaufmann D. PLoS One. 2012;7(12):e52473. doi: 10.1371/journal.pone.0052473. Epub 2012 Dec 21. PMID: 23285056 Free PMC article.
Partial Blindness to Submicron Topography in NF1 Haploinsufficient Cultured Fibroblasts Indicates a New Function of Neurofibromin in Regulation of Mechanosensoric. Kaufmann D, Hoesch J, Su Y, Deeg L, Mellert K, Spatz JP, Kemkemer R. Mol Syndromol. 2012 Oct;3(4):169-79. doi: 10.1159/000342698. Epub 2012 Sep 27. PMID: 23239959 Free PMC article.
Cyclic stretch increases splicing noise rate in cultured human fibroblasts. Uhl M, Mellert K, Striegl B, Deibler M, Lamla M, Spatz JP, Kemkemer R, Kaufmann D. BMC Res Notes. 2011 Oct 31;4:470. doi: 10.1186/1756-0500-4-470. PMID: 22040907 Free PMC article.
Aberrant Single Exon Skipping is not Altered by Age in Exons of NF1, RABAC1, AATF or PCGF2 in Human Blood Cells and Fibroblasts.Mellert K, Uhl M, Högel J, Lamla M, Kemkemer R, Kaufmann D. Genes (Basel). 2011 Aug 2;2(3):562-77. doi: 10.3390/genes2030562. PMID: 24710210 Free PMC article.