BIOQUANT

Linda Schuster

Research Interest

Recent developments in field of cancer research demonstrated a tight link between cancer cell’s specific gene expression and altered histone modifications and DNA methylation patterns. Evidence was found that either mutations in regulatory epigenetic proteins like histone demethylases or associated cofactors are major-driving forces for cancer progression. Prominent examples for such cofactors are mutations in IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) causing a neomorphic enzyme activity. The loss of those enzymes promotes the conversion of a-ketoglutarate (a-KG) to the oncometabolite (R)-2-hydroxyglutarate (R-2HG). This metabolite competes with a-KG and functional inhibits KDMs but also DNA demethylases resulting in large scale changes of the epigenetic landscape by creating hypermethylation profiles. As this gain of methylation impairs cellular differentiation promoting tumorigenesis, I examine the reversibility of R-2-HG induced changes in two relevant cancers, acute myeloid leukemia (AML) and glioblastoma. We aim to address this issue by linking gene expression profiles from RNA-seq with chromatin changes using ChIP-seq and ATAC-seq. Using state of the art techniques cell heterogeneity and drug response mechanisms will be investigated using single cell approaches. 

 

Scientific Background

  • Since 10/2018             PhD project on ‘Deregulated histone and DNA demethylation activity as a driver of tumorigenesis in glioblastoma and acute myeloid leukemia' in the Research Group of PD Dr. Karsten Rippe, Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg
  • 11/2015 – 08/2018      Research technician ‘Investigation of epigenetic mechanisms featuring in cancer development’ Research Group of Christoph Bock, PhD; Department of Medical Epigenomics,Center of Molecular Medicine (CeMM), Vienna, Austria 
  • 02/2015 – 10/2015      Master’s project on ‘Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages‘; Research group of Prof. Dr. Ben Forbes; Department of Drug Delivery, King’s College London, London, United Kingdom
  • 06/2014 – 12/2014      Research project on ‘The influence of different peritoneal dialysis fluids on the in vitro activity of various antibiotics’; Research group of Ao. Univ.-Prof. Dr. Heinz Burgmann; Department of Infectious Diseases and Tropical Medicine, General Hospital, Vienna, Austria
  • 10/2013 - 01/2016       Graduate studies (Master) of Molecular Biotechnology with specialization Drug Discovery at the University of Applied Sciences Vienna, Vienna, Austria
  • 02/2013 – 05/2013      Bachelor Thesis ‘Alpha Thalassaemia Diagnostics – Difficulties in detecting heterozygous deletions of entire exons’; Research group of Ao- Univ. Prof. Dr. Raute Sunder Plaßmann; Department of Laboratory Medicine – Molecular Biology, General Hospital, Vienna, Austria
  • 10/2010 – 07/2013      Undergraduate studies (Bachelor) of Biomedical Sciences University of Applied Sciences Vienna, Vienna, Austria

Publications

AF. Rendeiro, T. Krausgruber, N. Fortelny, F. Zhao, T. Penz, M.Farlik, LC. Schuster, A. Nemc, S. Tasnády, M Réti, Z. Mátrai, D. Alpar, C. Bödör, C. Schmidl, C. Bock, "Chromatin mapping and single-cell immune profiling define the temporal dynamics of ibrutinib drug response in chronic lymphocytic leukemia." Nat Commun (2019)

 

L. Selley#, LC. Schuster#, H. Marbach, T. Forsthuber, B. Forbes, TW. Grant, T. Sandstrom, N. Camina, TJ. Athersuch, I. Mudway, A. Kumar, "Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages." Metallomics (2019) #denotes equal contribution

 

F. Halbritter, M. Farlik, R. Schwentner, G. Jug, N. Fortelny, T. Schnoller, H. Pisa, LC. Schuster, A. Reinprecht, T.Czech, J. Gojo, W.Holter, M. Minkov, WM. Bauer, I. Simonitsch-Klupp, C. Bock and C. Hutter, "Epigenomics and Single-cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis." Cancer Discovery (2019)


P. Datlinger, AF. Rendeiro, C. Schmidl, T. Krausgruber, P. Traxler, J. Klughammer, LC. Schuster, A. Kuchler, D. Alpar, C Bock,“Pooled CRISPR screening with single-cell transcriptome readout.” Nat Methods (2017)


M. Kussmann, L. Schuster, S. Wrenger, P. Pichler, G. Reznicek, H. Burgmann, W. Poeppl, M. Zeitlinger, M. Wiesholzer, “Influence of different peritoneal dialysis fluids on the in vitro activity of cefepime, ciprofloxacin, ertapenem, meropenem and tobramycin against Escherichia coli.” Perit Dial Int (2016)


M. Kussmann, L. Schuster, M. Zeitlinger, P. Pichler, G. Reznicek, M. Wiesholzer, H. Burgmann, W. Poeppl, “The influence of different peritoneal dialysis fluids on the in vitro activity of ampicillin, daptomycin, and linezolid against Enterococcus faecalis.” Eur J Clin Microbiol Infect Dis. (2015)

 

Contact

Linda Schuster

DKFZ & BioQuant Center

Division of Chromatin Networks

Im Neuenheimer Feld 267-BQ24

69120 Heidelberg

Germany


BioQuant room 623

Tel.: +49-6221-54-51374

Fax: +49 6221 54 51487


e-mail: linda.schuster(at)dkfz.de