Lara Klett
Research Interest
At present, cancer therapy is changing fundamentally. As replacement for conventional therapy with cytotoxic agents, new individualized therapies are emerging treating patients with drugs specifically intervening molecular pathways with aberrant activity. Among those is a novel therapeutic approach for chronic lymphocytic leukemia (CLL) targeting aberrant B-cell receptor (BCR) signaling. As a deregulated chromatin landscape has been associated with the pathogenesis of CLL, I examine the impact of BCR signaling of malignant cells on the epigenetics landscape genome wide by measuring several chromatin features e.g. histone modifications and Tn5-transposase accessibility (ATAC-seq). In particular, I focus on the mapping of active enhancers to link them with the deregulated gene expression in CLL. In addition to the differences between patients and non-malignant controls as well as between patients, I am also interested in the genetic, epigenetic and transcriptomic intrapatient heterogeneity on the single cell level in response to treatment.
Scientific Background
- since 07/2015: PhD student at the German Cancer Research Center in the research group “Chromatin networks” of Prof. Dr. Karsten Rippe
- 04/2013 – 05/2013: Research intern in the “Systems Genetics and Precision Health” group of Prof. Dr. Lars Steinmetz at the European Molecular Biology Laboratory, Heidelberg
- 11/2012 – 12/2012: Research intern in the “Modelling of Biological Processes” group of Prof. Dr. Ursula Kummer at the University of Heidelberg
- 10/2011 – 6/2015: University of Heidelberg - Master program of Molecular Biosciences - Systems Biology (thesis in the “Systems Genetics and Precision Health” group of Prof. Dr. Lars Steinmetz at the European Molecular Biology Laboratory, Heidelberg)
- 10/2008 – 07/2011: University of Heidelberg - Bachelor program of Molecular and Cellular Biology (thesis in the department of “Human Molecular Genetics” at the Institute of „Human Genetics“, Prof. Dr. Gudrun Rappold)
Stipends
- PhD scholarship of the Helmholtz International Graduate School for Cancer Research, 2015
Publications
- Wierzbinska JA, Toth R, Ishaque N, Rippe K, Mallm JP, Klett L, Mertens D, Zenz T, Hielscher T, Seifert M, Küppers R, Assenov Y, Lutsik P, Stilgenbauer S, Roessner PM, Seiffert M, Byrd J, Oakes CC, Plass C & Lipka DB (2020). Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL.
Genome Med, accepted. biorxiv 933937. doi: 10.1101/2020.02.04.933937 - Mallm JP, Iskar M, Ishaque N, Klett LC, Kugler SJ, Muino JM, Teif VB, Poos AM, Großmann S, Erdel F, Tavernari D, Koser SD, Schumacher S, Brors B, König R, Remondini D, Vingron M, Stilgenbauer S, Lichter P, Zapatka M, Mertens D & Rippe K (2019). Linking aberrant chromatin features in chronic lymphocytic leukemia to deregulated transcription factor networks.
Mol Syst Biol 15, e8339. doi: 10.15252/msb.20188339 - Anuhar Chaturvedi, Lena Herbst, Stefan Pusch, Lara Klett, Ramya Goparaju, Damian Stichel, Stefan Kaulfuss, Olaf Panknin, Katja Zimmermann, Luisella Toschi, Roland Neuhaus, Andrea Haegebarth, Hartmut Rehwinkel, Holger Hess-Stump, Marcus Bauser, Tilmann Bochtler, Eduard A. Struys, Amit Sharma, Abdellatif Bakkali, Robert Geffers, Michelle Maria Araujo-Cruz, Felicitas Thol, Razif Gabdoulline, Arnold Ganser, Anthony D. Ho, Andreas von Deimling, Karsten Rippe, Michael Heuser, Alwin Krämer. (2017).
Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo.
Leukemia. DOI: 10.1038/leu.2017.46. - Jennifer Levering, Tomas Fiedler, Antje Sieg, Koen W van Grinsven, Silvio Hering, Nadine Veith, Brett G Olivier, Lara Klett, Jeroen Hugenholtz, Bas Teusink, Bernd Kreikemeyer, Ursula Kummer (2016)
Genome-scale reconstruction of the Streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets.
Journal of Biotechnology. 232 25–37. 10.1016/j.jbiotec.2016.01.035.
Contact
Lara Klett
DKFZ & BioQuant Center
Division of Chromatin Networks
Im Neuenheimer Feld 267-BQ24
69120 Heidelberg
Germany
BioQuant room 622a
Tel.: +49-6221-54-51373
Fax: +49 6221 54 51487
e-mail: l.klett(at)dkfz.de