Forscherdatenbank
Prof. Dr. Christoph Plass
Division of Epigenomics and Cancer Risk Factors
Im Neuenheimer Feld 280
69120 Heidelberg
Programm
Exploitation of Oncogenic Mechanisms (EOM)
Übersicht
Epigenetic determinants of molecular tumorigenesis, cancer risk and and prognosis
Epigenome-wide screens are being used to characterize cells and tissues in different states of normal differentiation or upon neoplastic transformation, to characterize genes identified as epigenetic targets, and to find biomarkers for early diagnosis or prognosis. As epigenetic regulation may be essentially reversible, e.g. by medical drugs or lifestyle changes, there is also strong interest in the molecular mechanisms leading to altered epigenetic patterns in cancer, and in identifying epigenetic markers for monitoring of chemoprevention and treatment responses.
Selected Publications
1. Lipka DB, Witte T, Toth R, Yang J, Wiesenfarth M, Nöllke P, Fischer A, Brocks D, Gu Z, Park J, Strahm B, Wlodarski M, Yoshimi A, Claus R, Lübbert M, Busch H, Boerries M, Hartmann M, Schönung M, Kilik U, Langstein J, Wierzbinska JA, Pabst C, Garg S, Catalá A, De Moerloose B, Dworzak M, Hasle H, Locatelli F, Masetti R, Schmugge M, Smith O, Stary J, Ussowicz M, van den Heuvel-Eibrink MM, Assenov Y, Schlesner M, Niemeyer C, Flotho C, Plass C. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia. Nature Communications (2017), 8(1), 2126.
2. Brocks D, Schmidt CR, Daskalakis M, Jang HS, Shah NM, Li D, Li J, Zhang B, Hou Y, Laudato S, Lipka DB, Schott J, Bierhoff H, Assenov Y, Helf M, Ressnerova A, Islam MS, Lindroth AM, Haas S, Essers M, Imbusch CD, Brors B, Oehme I, Witt O, Lübbert M, Mallm JP, Rippe K, Will R, Weichenhan D, Stoecklin G, Gerhäuser C, Oakes CC, Wang T, Plass C. DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats. Nature Genetics (2017), 49(7), 1052-1060.
3. Oakes CC, Seifert M, Assenov Y, Gu L, Przekopowitz M, Ruppert AS, Wang Q, Imbusch CD, Serva A, Koser SD, Brocks D, Lipka DB, Bogatyrova O, Weichenhan D, Brors B, Rassenti L, Kipps TJ, Mertens D, Zapatka M, Lichter P, Döhner H, Küppers R, Zenz T, Stilgenbauer S, Byrd JC, Plass C. DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia. Nature Genetics (2016), 48(3), 253-264.
4. Claus R, Lucas DM, Stilgenbauer S, Ruppert AS, Yu L, Zucknick M, Mertens D, Bühler A, Oakes CC, Larson RA, Kay NE, Jelinek DF, Kipps TJ, Rassenti LZ, Gribben JG, Döhner H, Heerema NA, Marcucci G, Plass C, Byrd JC. Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia. Journal of Clinical Oncology (2012) 30(20), 2483-2491.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.