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Section Translational Cancer Epigenomics

Overview

Epigenetic patterns enable the different cell types of our body to specifically read and interpret the information stored in the DNA according to their specific needs. Epigenetic processes are therefore dynamically regulating cellular differentiation processes during embryonic development and all the way to the adult organism, but at the same time they are also of crucial importance for homeostatic processes.



The Team of Translational Cancer epigenomics

Thus, the coordinated programming of the epigenetic landscape is essential for intact differentiation and guarantees the establishment of stable cell phenotypes as a result of differentiation processes. However, due to their intrinsically reversible nature, epigenetic marks also provide the organism with the possibility of dynamic adaptation to changing environmental conditions. Under physiological settings, the epigenome of a cell thus integrates information on cell identity or function as well as on present or past environmental influences and on the age of the cell. Significant changes of the epigenome can be observed in many diseases, including cancer.

In our group we investigate the epigenetic regulation of normal and malignant differentiation processes. To this end, we use state-of-the-art techniques including single cell methods for genome, epigenome and transcriptome analysis (e.g. whole-genome bisulfite sequencing, ATAC-seq, ACT-seq, RNA-seq, scM&T-seq) to analyze epigenetic patterns and their dynamics in normal hematopoiesis as well as in hematopoietic neoplasms. In addition, we are investigating the functional and epigenetic consequences of dysregulated expression of oncogenes and epigenetic modulators using several in vitro and in vivo models.

The knowledge gained will allow us to develop an in-depth understanding of the malignant transformation process and how it can be prevented or therapeutically reversed.

Within the NCT MASTER program (https://www.nct-heidelberg.de/forschung/molecular-stratification/master.html) as well as in close cooperation with clinical study groups, such as the EWOG-MDS study group (https://ewog-mds-saa.org/), we take advantage of the cell type specificity of epigenetic patterns for precision oncology questions. Here, our focus is on the development and validation of new diagnostic, prognostic and predictive biomarkers that enable precise diagnosis or targeted, risk-adapted therapy.

  • Juvenile myelomonocytic leukemia (JMML)
  • Epigenetic regulation of normal hematopoiesis
  • Epigenetic aberrations in clonal hematopoeisis and pre-leukemia
  • Tumorclassification using DNA methylation patterns


Principle Investigator

Priv.-Doz. Dr. med. Daniel Lipka

Priv.-Doz. Dr. med. Daniel Lipka



Postdoctoral Fellows

Dr. rer. nat. Mark Hartmann

Dr. rer. nat. Mark Hartmann



Dr. rer. nat. Maximilian Schönung



Doctoral students



Anna Maria Dobberkau

Anna Maria Dobberkau
(MD Student)



Mariam Hakobyan

Mariam Hakobyan
(PhD Student)



Panna Lajer
(PhD Student)



Stephen Krämer

Stephen Krämer
(PhD student; joined supervision together with the DKFZ Division „Bioinformatics und Omics Data Analystics“)





Undergraduate Students



Jana Gramer
lab internship



Franziska Oberhammer
master student



Hannah Rohdjeß
master student



Lea Vogt
master student







Alumni

  • Valentin Maurer (master student)
  • Qi An (PhD student)
  • Emely Kleinert (lab technician)
  • Dr. rer. nat. Sina Stäble (PhD student & postdoctoral fellow)
  • Carlotta Brüggen (bachelor student)
  • Dr. rer. nat. Jens Langstein (PhD student)
  • Dr. rer. nat. Justyna Wierzbinska (PhD student & postdoctoral fellow)
  • Oliver Mücke (lab technician)
  • Katharina Mauel (HiWi)
  • Stephanie Schmitz (lab internship)
  • Hannah Wieler (lab internship)
  • Menna Mubarak (lab internship)
  • Jeyan Jayarajan (master student)
  • Umut Kilik (master student)
  • Julia Meßmer (lab internship)
  • Pirmin Killinger (bachelor student)


« all recent publications on Pubmed

2023:

  • Weichenhan, D., Riedel A., Meinen C., Basic A., Toth R., Bahr M., Lutsik P., Hey J., Sollier E., Toprak U.H., Kelekci S., Lin Y.Y., Hakobyan M., Touzart A., Goyal A., Wierzbinska J.A., Schlesner M., Westermann F., Lipka D.B.Plass C. "Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking." Leukemia. (2023) 37(5):1147-1150.
  • Schonung, M., Hartmann M., Kramer S., Stable S., Hakobyan M., Kleinert E., Aurich T., Cobanoglu D., Heidel F.H., Frohling S., Milsom M.D., Schlesner M., Lutsik P.Lipka D.B. "Dynamic DNA methylation reveals novel cis-regulatory elements in mouse hematopoiesis." Exp Hematol. (2023) 117:24-42 e27.
  • Manoochehri, M., Borhani N., Gerhauser C., Assenov Y., Schonung M., Hielscher T., Christensen B.C., Lee M.K., Grone H.J., Lipka D.B., Bruning T., Brauch H., Ko Y.D.Hamann U. "DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy." Int J Cancer. (2023) 152(5):1025-1035.
  • Hey, J., Halperin C., Hartmann M., Mayer S., Schonung M., Lipka D.B., Scherz-Shouval R.Plass C. "DNA methylation landscape of tumor-associated macrophages reveals pathways, transcription factors and prognostic value relevant to triple-negative breast cancer patients." Int J Cancer. (2023) 152(6):1226-1242.

 

2022:

  • Zioni, N., Bercovich A., Chapal-Ilani N., Solomon A., Kopitman E., Sacma M., Hartmut G., Scheller M., Müller-Tidow C., Lipka D., Shlush E., Minden M., Kaushansky N.Shlush L.I. "Inflammatory signals from fatty bone marrow supports the early stages of DNMT3a driven clonal hematopoiesis." bioRxiv. (2022):2022.2001.2013.476218.
  • Weichenhan, D., Lipka D.B., Lutsik P., Goyal A.Plass C. "Epigenomic technologies for precision oncology." Semin Cancer Biol. (2022) 84:60-68.
  • Niger, M., Nichetti F., Casadei-Gardini A., Morano F., Pircher C., Tamborini E., Perrone F., Canale M., Lipka D.B., Vingiani A., Agnelli L., Dobberkau A., Hullein J., Korell F., Heilig C.E., Pusceddu S., Corti F., Droz M., Ulivi P., Prisciandaro M., Antista M., Bini M., Cattaneo L., Milione M., Glimm H., Kohler B.C., Pruneri G., Hubschmann D., Frohling S., Mazzaferro V., Pietrantonio F., Di Bartolomeo M.de Braud F. "MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers." Mol Oncol. (2022) 16(14):2733-2746.
  • Jahn, A., Rump A., Widmann T.J., Heining C., Horak P., Hutter B., Paramasivam N., Uhrig S., Gieldon L., Drukewitz S., Kubler A., Bermudez M., Hackmann K., Porrmann J., Wagner J., Arlt M., Franke M., Fischer J., Kowalzyk Z., William D., Weth V., Oster S., Frohlich M., Hullein J., Valle Gonzalez C., Kreutzfeldt S., Mock A., Heilig C.E., Lipka D.B., Mohrmann L., Hanf D., Oles M., Teleanu V., Allgauer M., Ruhnke L., Kutz O., Knurr A., Lassmann A., Endris V., Neumann O., Penzel R., Beck K., Richter D., Winter U., Wolf S., Pfutze K., Georg C., Meissburger B., Buchhalter I., Augustin M., Aulitzky W.E., Hohenberger P., Kroiss M., Schirmacher P., Schlenk R.F., Keilholz U., Klauschen F., Folprecht G., Bauer S., Siveke J.T., Brandts C.H., Kindler T., Boerries M., Illert A.L., von Bubnoff N., Jost P.J., Metzeler K.H., Bitzer M., Schulze-Osthoff K., von Kalle C., Brors B., Stenzinger A., Weichert W., Hubschmann D., Frohling S., Glimm H., Schrock E.Klink B. "Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers." Ann Oncol. (2022) 33(11):1186-1199.
  • Mohrmann, L., Werner M., Oles M., Mock A., Uhrig S., Jahn A., Kreutzfeldt S., Frohlich M., Hutter B., Paramasivam N., Richter D., Beck K., Winter U., Pfutze K., Heilig C.E., Teleanu V., Lipka D.B., Zapatka M., Hanf D., List C., Allgauer M., Penzel R., Ruter G., Jelas I., Hamacher R., Falkenhorst J., Wagner S., Brandts C.H., Boerries M., Illert A.L., Metzeler K.H., Westphalen C.B., Desuki A., Kindler T., Folprecht G., Weichert W., Brors B., Stenzinger A., Schrock E., Hubschmann D., Horak P., Heining C., Frohling S.Glimm H. "Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity." Nat Commun. (2022) 13(1):4485.
  • Meier, R., Greve G., Zimmer D., Bresser H., Berberich B., Langova R., Stomper J., Rubarth A., Feuerbach L., Lipka D.B., Hey J., Gruning B., Brors B., Duyster J., Plass C., Becker H.Lubbert M. "The antileukemic activity of decitabine upon PML/RARA-negative AML blasts is supported by all-trans retinoic acid: in vitro and in vivo evidence for cooperation." Blood Cancer J. (2022) 12(8):122.
  • Maron, R.C., Hekler A., Haggenmuller S., von Kalle C., Utikal J.S., Muller V., Gaiser M., Meier F., Hobelsberger S., Gellrich F.F., Sergon M., Hauschild A., French L.E., Heinzerling L., Schlager J.G., Ghoreschi K., Schlaak M., Hilke F.J., Poch G., Korsing S., Berking C., Heppt M.V., Erdmann M., Haferkamp S., Schadendorf D., Sondermann W., Goebeler M., Schilling B., Kather J.N., Frohling S., Lipka D.B., Krieghoff-Henning E.Brinker T.J. "Model soups improve performance of dermoscopic skin cancer classifiers." Eur J Cancer. (2022) 173:307-316.
  • Heilig, C.E., Lassmann A., Mughal S.S., Mock A., Pirmann S., Teleanu V., Renner M., Andresen C., Kohler B.C., Aybey B., Bauer S., Siveke J.T., Hamacher R., Folprecht G., Richter S., Schrock E., Brandts C.H., Ahrens M., Hohenberger P., Egerer G., Kindler T., Boerries M., Illert A.L., von Bubnoff N., Apostolidis L., Jost P.J., Westphalen C.B., Weichert W., Keilholz U., Klauschen F., Beck K., Winter U., Richter D., Mohrmann L., Bitzer M., Schulze-Osthoff K., Brors B., Mechtersheimer G., Kreutzfeldt S., Heining C., Lipka D.B., Stenzinger A., Schlenk R.F., Horak P., Glimm H., Hubschmann D.Frohling S. "Gene expression-based prediction of pazopanib efficacy in sarcoma." Eur J Cancer. (2022) 172:107-118.
  • Hauser, K., Kurz A., Haggenmuller S., Maron R.C., von Kalle C., Utikal J.S., Meier F., Hobelsberger S., Gellrich F.F., Sergon M., Hauschild A., French L.E., Heinzerling L., Schlager J.G., Ghoreschi K., Schlaak M., Hilke F.J., Poch G., Kutzner H., Berking C., Heppt M.V., Erdmann M., Haferkamp S., Schadendorf D., Sondermann W., Goebeler M., Schilling B., Kather J.N., Frohling S., Lipka D.B., Hekler A., Krieghoff-Henning E.Brinker T.J. "Explainable artificial intelligence in skin cancer recognition: A systematic review." Eur J Cancer. (2022) 167:54-69.
  • Harrison, C., Heidel F.H., Vannucchi A.M., Kiladjian J.J., Hayat A., Passamonti F., Conneally E., Kindler T., Martino B., Lipka D.B., Stefanelli T., Roussou P., Germano D., Ewan J.Ribrag V. "A Phase Ib Dose-finding Study of Panobinostat and Ruxolitinib in Myelofibrosis." Hemasphere. (2022) 6(8):e757.
  • Dietlein, N., Wang X., Metz J., Disson O., Shang F., Beyersdorffer C., Rodriguez Correa E., Lipka D.B., Begus-Nahrmann Y., Kosinsky R.L., Johnsen S.A., Lecuit M., Hofer T.Rodewald H.R. "Usp22 is an intracellular regulator of systemic emergency hematopoiesis." Sci Immunol. (2022) 7(78):eabq2061.
  • Niger M., Nichetti F., Casadei-Gardini A., Morano F., Pircher C., Tamborini E., Perrone F., Canale M., Lipka D.B., Vingiani A., Agnelli L., Dobberkau A., Hullein J., Korell F., Heilig C.E., Pusceddu S., Corti F., Droz M., Ulivi P., Prisciandaro M., Antista M., Bini M., Cattaneo L., Milione M., Glimm H., Kohler B.C., Pruneri G., Hubschmann D., Frohling S., Mazzaferro V., Pietrantonio F., Di Bartolomeo M., de Braud F. MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers. Mol Oncol. (2022);16(14):2733-46.
  • Mohrmann L., Werner M., Oles M., Mock A., Uhrig S., Jahn A., Kreutzfeldt S., Frohlich M., Hutter B., Paramasivam N., Richter D., Beck K., Winter U., Pfutze K., Heilig C.E., Teleanu V., Lipka D.B., Zapatka M., Hanf D., List C., Allgauer M., Penzel R., Ruter G., Jelas I., Hamacher R., Falkenhorst J., Wagner S., Brandts C.H., Boerries M., Illert A.L., Metzeler K.H., Westphalen C.B., Desuki A., Kindler T., Folprecht G., Weichert W., Brors B., Stenzinger A., Schrock E., Hubschmann D., Horak P., Heining C., Frohling S., Glimm H. Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity. Nature Communications. (2022);13(1):4485
  • Czeh M., Stable S., Kramer S., Tepe L., Talyan S., Carrelha J., Meng Y., Heitplatz B., Schwabenland M., Milsom M.D., Plass C., Prinz M., Schlesner M., Andrade-Navarro M.A., Nerlov C., Jacobsen S.E.W., Lipka D.B., Rosenbauer F. DNMT1 Deficiency Impacts on Plasmacytoid Dendritic Cells in Homeostasis and Autoimmune Disease. J Immunol. (2022);208(2):358-70.
  • Bogeska R., Mikecin A.M., Kaschutnig P., Fawaz M., Buchler-Schaff M., Le D., Ganuza M., Vollmer A., Paffenholz S.V., Asada N., Rodriguez-Correa E., Frauhammer F., Buettner F., Ball M., Knoch J., Stable S., Walter D., Petri A., Carreno-Gonzalez M.J., Wagner V., Brors B., Haas S., Lipka D.B., Essers M.A.G., Weru V., Holland-Letz T., Mallm J.P., Rippe K., Kramer S., Schlesner M., McKinney Freeman S., Florian M.C., King K.Y., Frenette P.S., Rieger M.A., Milsom M.D. Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell. (2022);29(8):1273-84 e8.

 

2021:

  • Schonung M., Meyer J., Nollke P., Olshen A.B., Hartmann M., Murakami N., Wakamatsu M., Okuno Y., Plass C., Loh M.L., Niemeyer C.M., Muramatsu H., Flotho C., Stieglitz E., Lipka D.B. International Consensus Definition of DNA Methylation Subgroups in Juvenile Myelomonocytic Leukemia. Clin Cancer Res. (2021);27(1):158-68.
  • Schonung M., Hess J., Bawidamann P., Stable S., Hey J., Langstein J., Assenov Y., Weichenhan D., Lutsik P., Lipka D.B. AmpliconDesign - an interactive web server for the design of high-throughput targeted DNA methylation assays. Epigenetics. (2021);16(9):933-9.
  • Zanetti, C., Kumar R., Ender J., Godavarthy P.S., Hartmann M., Hey J., Breuer K., Weissenberger E.S., Minciacchi V.R., Karantanou C., Gu Z., Roberts K.G., Metzler M., Stock W., Mullighan C.G., Bloomfield C.D., Filmann N., Bankov K., Hartmann S., Hasserjian R.P., Cousins A.F., Halsey C., Plass C., Lipka D.B.Krause D.S. "The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13." Blood. (2021) 138(19):1870-1884.
  • Scheller M., Ludwig A.K., Göllner S., Rohde C., Krämer S., Stäble S., Janssen M., Müller J.-A., He L., Bäumer N., Arnold C., Gerß J., Schönung M., Thiede C., Niederwieser C., Niederwieser D., Serve H., Berdel W.E., Thiem U., Hemmerling I., Leuschner F., Plass C., Schlesner M., Zaugg J., Milsom M.D., Trumpp A., Pabst C., Lipka D.B., Müller-Tidow C. Hotspot DNMT3A mutations in clonal hematopoiesis and acute myeloid leukemia sensitize cells to azacytidine via viral mimicry response. Nature Cancer. (2021);2(5):527-44.
  • Niemoller C., Wehrle J., Riba J., Claus R., Renz N., Rhein J., Bleul S., Stosch J.M., Duyster J., Plass C., Lutsik P., Lipka D.B., Lubbert M., Becker H. Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction. Commun Biol. (2021);4(1):153.
  • Niemeyer C.M., Flotho C., Lipka D.B., Starý J., Rössig C., Baruchel A., Klingebiel T., Micalizzi C., Michel G., Nysom K., Rives S., Schmugge Liner M., Zecca M., Schönung M., Baumann I., Nöllke P., Benettaib B., Biserna N., Poon J., Simcock M., Patturajan M., Menezes D., Gaudy A., Van Den Heuvel-Eibrink M.M., Locatelli F. Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial. Blood Advances. (2021);5(14):2901-8.
  • Horak P., Heining C., Kreutzfeldt S., Hutter B., Mock A., Hullein J., Frohlich M., Uhrig S., Jahn A., Rump A., Gieldon L., Mohrmann L., Hanf D., Teleanu V., Heilig C.E., Lipka D.B., Allgauer M., Ruhnke L., Lassmann A., Endris V., Neumann O., Penzel R., Beck K., Richter D., Winter U., Wolf S., Pfutze K., Georg C., Meissburger B., Buchhalter I., Augustin M., Aulitzky W.E., Hohenberger P., Kroiss M., Schirmacher P., Schlenk R.F., Keilholz U., Klauschen F., Folprecht G., Bauer S., Siveke J.T., Brandts C.H., Kindler T., Boerries M., Illert A.L., von Bubnoff N., Jost P.J., Spiekermann K., Bitzer M., Schulze-Osthoff K., von Kalle C., Klink B., Brors B., Stenzinger A., Schrock E., Hubschmann D., Weichert W., Glimm H., Frohling S. Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Cancer Discovery. (2021);11(11):2780-95.

 

2020:

  • Wierzbinska J.A., Toth R., Ishaque N., Rippe K., Mallm J.P., Klett L.C., Mertens D., Zenz T., Hielscher T., Seifert M., Kuppers R., Assenov Y., Lutsik P., Stilgenbauer S., Roessner P.M., Seiffert M., Byrd J., Oakes C.C., Plass C. and Lipka D.B. Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL. Genome Med (2020);12(1):29.
  • Sill M., Plass C., Pfister S.M. and Lipka D.B. Molecular tumor classification using DNA methylome analysis. Hum Mol Genet (2020).
  • Mayakonda A., Schonung M., Hey J., Batra R.N., Feuerstein-Akgoz C., Kohler K., Lipka D.B., Sotillo R., Plass C., Lutsik P., Toth R. Methrix: an R/bioconductor package for systematic aggregation and analysis of bisulfite sequencing data. Bioinformatics. 2020.
  • Heilig C.E., Horak P., Lipka D.B., Mock A., Uhrig S., Kreutzfeldt S., Richter S., Gieldon L., Frohlich M., Hutter B., Hubschmann D., Teleanu V., Schmier J.W., Philipzen J., Beuthien-Baumann B., Schrock E., von Deimling A., Bauer S., Heining C., Mechtersheimer G., Stenzinger A., Brors B., Wardelmann E., Glimm H., Hartmann W. and Frohling S. Germline SDHB-inactivating mutation in gastric spindle cell sarcoma. Genes Chromosomes Cancer (2020);59(10):601-608.

 

2019:

  • Schubert C., Allhoff M., Tillmann S., Maie T., Costa I.G., Lipka D.B., Schemionek M., Feldberg K., Baumeister J., Brummendorf T.H., Chatain N. and Koschmieder S. Differential roles of STAT1 and STAT2 in the sensitivity of JAK2V617F- vs. BCR-ABL-positive cells to interferon alpha. J Hematol Oncol (2019);12(1):36.
  • Orouji E., Federico A., Larribere L., Novak D., Lipka D.B., Assenov Y., Sachindra S., Huser L., Granados K., Gebhardt C., Plass C., Umansky V. and Utikal J. Histone methyltransferase SETDB1 contributes to melanoma tumorigenesis and serves as a new potential therapeutic target. Int J Cancer (2019);145(12):3462-3477.
  • Krombholz C.F., Gallego-Villar L., Sahoo S.S., Panda P.K., Wlodarski M.W., Aumann K., Hartmann M., Lipka D.B., Daskalakis M., Plass C., Niemeyer C.M., Erlacher M. and Flotho C. Azacitidine is effective for targeting leukemia-initiating cells in juvenile myelomonocytic leukemia. Leukemia (2019);33(7):1805-1810.
  • Goeppert B., Toth R., Singer S., Albrecht T., Lipka D.B., Lutsik P., Brocks D., Baehr M., Muecke O., Assenov Y., Gu L., Endris V., Stenzinger A., Mehrabi A., Schirmacher P., Plass C., Weichenhan D. and Roessler S. Integrative Analysis Defines Distinct Prognostic Subgroups of Intrahepatic Cholangiocarcinoma. Hepatology (2019);69(5):2091-2106.
  • Garg S., Reyes-Palomares A., He L., Bergeron A., Lavallee V.P., Lemieux S., Gendron P., Rohde C., Xia J., Jagdhane P., Muller-Tidow C., Lipka D.B., Imren S., Humphries R.K., Waskow C., Vick B., Jeremias I., Richard-Carpentier G., Hebert J., Sauvageau G., Zaugg J.B., Barabe F. and Pabst C. Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML. Blood (2019);134(3):263-276.

 

2018:

  • Schlereth K., Weichenhan D., Bauer T., Heumann T., Giannakouri E., Lipka D., Jaeger S., Schlesner M., Aloy P., Eils R., Plass C. and Augustin H.G. The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium. Elife (2018);7.
  • Lipka D.B., Lutsik P. and Plass C. From Basic Knowledge to Effective Therapies. Cancer Cell (2018);34(6):871-873.
  • Langstein J., Milsom M.D. and Lipka D.B. Impact of DNA methylation programming on normal and pre-leukemic hematopoiesis. Semin Cancer Biol (2018);51:89-100.
  • Grigoryan A., Guidi N., Senger K., Liehr T., Soller K., Marka G., Vollmer A., Markaki Y., Leonhardt H., Buske C., Lipka D.B., Plass C., Zheng Y., Mulaw M.A., Geiger H. and Florian M.C. LaminA/C regulates epigenetic and chromatin architecture changes upon aging of hematopoietic stem cells. Genome Biol (2018);19(1):189.

 

2017:

  • Stieglitz E., Mazor T., Olshen A.B., Geng H., Gelston L.C., Akutagawa J., Lipka D.B., Plass C., Flotho C., Chehab F.F., Braun B.S., Costello J.F. and Loh M.L. Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia. Nat Commun (2017);8(1):2127.
  • Lipka D.B., Witte T., Toth R., Yang J., Wiesenfarth M., Nollke P., Fischer A., Brocks D., Gu Z., Park J., Strahm B., Wlodarski M., Yoshimi A., Claus R., Lubbert M., Busch H., Boerries M., Hartmann M., Schonung M., Kilik U., Langstein J., Wierzbinska J.A., Pabst C., Garg S., Catala A., De Moerloose B., Dworzak M., Hasle H., Locatelli F., Masetti R., Schmugge M., Smith O., Stary J., Ussowicz M., van den Heuvel-Eibrink M.M., Assenov Y., Schlesner M., Niemeyer C., Flotho C. and Plass C. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nat Commun (2017);8(1):2126.
  • Brocks D., Schmidt C.R., Daskalakis M., Jang H.S., Shah N.M., Li D., Li J., Zhang B., Hou Y., Laudato S., Lipka D.B., Schott J., Bierhoff H., Assenov Y., Helf M., Ressnerova A., Islam M.S., Lindroth A.M., Haas S., Essers M., Imbusch C.D., Brors B., Oehme I., Witt O., Lubbert M., Mallm J.P., Rippe K., Will R., Weichenhan D., Stoecklin G., Gerhauser C., Oakes C.C., Wang T. and Plass C. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nat Genet (2017);49(7):1052-1060.

 

2016:

  • Wilhelm T., Lipka D.B., Witte T., Wierzbinska J.A., Fluhr S., Helf M., Mucke O., Claus R., Konermann C., Nollke P., Niemeyer C.M., Flotho C. and Plass C. Epigenetic silencing of AKAP12 in juvenile myelomonocytic leukemia. Epigenetics (2016);11(2):110-9.
  • Slabicki M., Lee K.S., Jethwa A., Sellner L., Sacco F., Walther T., Hullein J., Dietrich S., Wu B., Lipka D.B., Oakes C.C., Mamidi S., Pyrzynska B., Winiarska M., Oles M., Seifert M., Plass C., Kirschfink M., Boettcher M., Golab J., Huber W., Frohling S. and Zenz T. Dissection of CD20 regulation in lymphoma using RNAi. Leukemia (2016);30(12):2409-2412.
  • Schworer S., Becker F., Feller C., Baig A.H., Kober U., Henze H., Kraus J.M., Xin B., Lechel A., Lipka D.B., Varghese C.S., Schmidt M., Rohs R., Aebersold R., Medina K.L., Kestler H.A., Neri F., von Maltzahn J., Tumpel S. and Rudolph K.L. Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals. Nature (2016);540(7633):428-432.
  • Oakes C.C., Seifert M., Assenov Y., Gu L., Przekopowitz M., Ruppert A.S., Wang Q., Imbusch C.D., Serva A., Koser S.D., Brocks D., Lipka D.B., Bogatyrova O., Weichenhan D., Brors B., Rassenti L., Kipps T.J., Mertens D., Zapatka M., Lichter P., Dohner H., Kuppers R., Zenz T., Stilgenbauer S., Byrd J.C. and Plass C. DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia. Nat Genet (2016);48(3):253-64.
  • Merkle R., Steiert B., Salopiata F., Depner S., Raue A., Iwamoto N., Schelker M., Hass H., Wasch M., Bohm M.E., Mucke O., Lipka D.B., Plass C., Lehmann W.D., Kreutz C., Timmer J., Schilling M. and Klingmuller U. Identification of Cell Type-Specific Differences in Erythropoietin Receptor Signaling in Primary Erythroid and Lung Cancer Cells. PLoS Comput Biol (2016);12(8):e1005049.
  • Lipka D.B., Wagner M.C., Dziadosz M. and Fischer T. Prolonged cellular midostaurin retention suggests potential alternative dosing strategies for FLT3-ITD-positive leukemias. Leukemia (2016);30(10):2090-2093.
  • Fluhr S., Boerries M., Busch H., Symeonidi A., Witte T., Lipka D.B., Mucke O., Nollke P., Krombholz C.F., Niemeyer C.M., Plass C. and Flotho C. CREBBP is a target of epigenetic, but not genetic, modification in juvenile myelomonocytic leukemia. Clin Epigenetics (2016);8:50.

 

2015:

  • Schnoder T.M., Arreba-Tutusaus P., Griehl I., Bullinger L., Buschbeck M., Lane S.W., Dohner K., Plass C., Lipka D.B., Heidel F.H. and Fischer T. Epo-induced erythroid maturation is dependent on Plcgamma1 signaling. Cell Death Differ (2015);22(6):974-85.
  • Ohrnberger S., Thavamani A., Braeuning A., Lipka D.B., Kirilov M., Geffers R., Autenrieth S.E., Romer M., Zell A., Bonin M., Schwarz M., Schutz G., Schirmacher P., Plass C., Longerich T. and Nordheim A. Dysregulated serum response factor triggers formation of hepatocellular carcinoma. Hepatology (2015);61(3):979-89.

 

2014:

  • Wolleschak D., Mack T.S., Perner F., Frey S., Schnoder T.M., Wagner M.C., Hoding C., Pils M.C., Parkner A., Kliche S., Schraven B., Hebel K., Brunner-Weinzierl M., Ranjan S., Isermann B., Lipka D.B., Fischer T. and Heidel F.H. Clinically relevant doses of
  • FLT3-kinase inhibitors quizartinib and midostaurin do not impair T-cell reactivity and function. Haematologica (2014);99(6):e90-3.
  • Sonnet M., Claus R., Becker N., Zucknick M., Petersen J., Lipka D.B., Oakes C.C., Andrulis M., Lier A., Milsom M.D., Witte T., Gu L., Kim-Wanner S.Z., Schirmacher P., Wulfert M., Gattermann N., Lubbert M., Rosenbauer F., Rehli M., Bullinger L., Weichenhan D. and Plass C. Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia. Genome Med (2014);6(4):34.
  • Poetsch A.R., Lipka D.B., Witte T., Claus R., Nollke P., Zucknick M., Olk-Batz C., Fluhr S., Dworzak M., De Moerloose B., Stary J., Zecca M., Hasle H., Schmugge M., van den Heuvel-Eibrink M.M., Locatelli F., Niemeyer C.M., Flotho C. and Plass C. RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia. Epigenetics (2014);9(9):1252-60.
  • Lipka D.B., Wang Q., Cabezas-Wallscheid N., Klimmeck D., Weichenhan D., Herrmann C., Lier A., Brocks D., von Paleske L., Renders S., Wunsche P., Zeisberger P., Gu L., Haas S., Essers M.A., Brors B., Eils R., Trumpp A., Milsom M.D. and Plass C. Identification of DNA methylation changes at cis-regulatory elements during early steps of HSC differentiation using tagmentation-based whole genome bisulfite sequencing. Cell Cycle (2014);13(22):3476-87.
  • Cabezas-Wallscheid N., Klimmeck D., Hansson J., Lipka D.B., Reyes A., Wang Q., Weichenhan D., Lier A., von Paleske L., Renders S., Wunsche P., Zeisberger P., Brocks D., Gu L., Herrmann C., Haas S., Essers M.A.G., Brors B., Eils R., Huber W., Milsom M.D., Plass C., Krijgsveld J. and Trumpp A. Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis. Cell Stem Cell (2014);15(4):507-522.
  • Brocks D., Assenov Y., Minner S., Bogatyrova O., Simon R., Koop C., Oakes C., Zucknick M., Lipka D.B., Weischenfeldt J., Feuerbach L., Cowper-Sal Lari R., Lupien M., Brors B., Korbel J., Schlomm T., Tanay A., Sauter G., Gerhauser C., Plass C. and Project I.E.O.P.C. Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer. Cell Rep (2014);8(3):798-806.

 

2013:

  • Wagner M.C., Dziadosz M., Melo J.V., Heidel F., Fischer T. and Lipka D.B. Nilotinib shows prolonged intracellular accumulation upon pulse-exposure: a novel mechanism for induction of apoptosis in CML cells. Leukemia (2013);27(7):1567-70.
  • Lipka D.B., Kuck D., Kliem C. and Gerhauser C. Substituted purine and 7-deazapurine compounds as modulators of epigenetic enzymes: a patent evaluation (WO2012075381). Expert Opin Ther Pat (2013);23(4):537-43.

 

2012:

  • Lipka D.B., Wagner M.C., Dziadosz M., Schnoder T., Heidel F., Schemionek M., Melo J.V., Kindler T., Muller-Tidow C., Koschmieder S. and Fischer T. Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells. PLoS One (2012);7(7):e40853.
  • Heidel F.H., Mack T.S., Razumovskaya E., Blum M.C., Lipka D.B., Ballaschk A., Kramb J.P., Plutizki S., Ronnstrand L., Dannhardt G. and Fischer T. 3,4-Diarylmaleimides-a novel class of kinase inhibitors-effectively induce apoptosis in FLT3-ITD-dependent cells. Ann Hematol (2012);91(3):331-44.

 

2010:

  • Kindler T., Lipka D.B. and Fischer T. FLT3 as a therapeutic target in AML: still challenging after all these years. Blood (2010);116(24):5089-102.

 

2009:

  • Kreft A., Springer E., Lipka D.B. and Kirkpatrick C.J. Wild-type JAK2 secondary acute erythroleukemia developing after JAK2-V617F-mutated primary myelofibrosis. Acta Haematol (2009);122(1):36-8.
  • Heidel F., Lipka D.B., Mirea F.K., Mahboobi S., Grundler R., Kancha R.K., Duyster J., Naumann M., Huber C., Bohmer F.D. and Fischer T. Bis(1H-indol-2-yl)methanones are effective inhibitors of FLT3-ITD tyrosine kinase and partially overcome resistance to PKC412A in vitro. Br J Haematol (2009);144(6):865-74.

 

2008:

  • Kasper S., Breitenbuecher F., Hoehn Y., Heidel F., Lipka D.B., Markova B., Huber C., Kindler T. and Fischer T. The kinase inhibitor LS104 induces apoptosis, enhances cytotoxic effects of chemotherapeutic drugs and is targeting the receptor tyrosine kinase FLT3 in acute myeloid leukemia. Leuk Res (2008);32(11):1698-708.

 

2007:

  • Heidel F., Lipka D.B., von Auer C., Huber C., Scharrer I. and Hess G. Addition of rituximab to standard therapy improves response rate and progression-free survival in relapsed or refractory thrombotic thrombocytopenic purpura and autoimmune haemolytic anaemia. Thromb Haemost (2007);97(2):228-33.

 

2006:

  • Rucker F.G., Bullinger L., Schwaenen C., Lipka D.B., Wessendorf S., Frohling S., Bentz M., Miller S., Scholl C., Schlenk R.F., Radlwimmer B., Kestler H.A., Pollack J.R., Lichter P., Dohner K. and Dohner H. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol (2006);24(24):3887-94.
  • Heidel F., Solem F.K., Breitenbuecher F., Lipka D.B., Kasper S., Thiede M.H., Brandts C., Serve H., Roesel J., Giles F., Feldman E., Ehninger G., Schiller G.J., Nimer S., Stone R.M., Wang Y., Kindler T., Cohen P.S., Huber C. and Fischer T. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood (2006);107(1):293-300.
  • Frohling S., Lipka D.B., Kayser S., Scholl C., Schlenk R.F., Dohner H., Gilliland D.G., Levine R.L. and Dohner K. Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7. Blood (2006);107(3):1242-3.

Documents to apply for access to TCE data in the European Genome-Phenome Archive (EGA)

Software, web tools & analysis scripts

Section Translational Cancer epigenomics
Department of Translational Medical Oncology
Deutsches Krebsforschungszentrum (DKFZ) & Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Im Neuenheimer Feld 581
69120 Heidelberg

Tel.: +49 6221 42 1603
E-Mail: d.lipka[at]dkfz.de
Twitter: @TransCanEpi
www.translational-cancer-epigenomics.de