Project (André Fischer)

Disorders of the heart and the brain are leading causes of disability and death worldwide. Aberrant gene expression is a hallmark of such multifactorial heart & brain diseases that arise on the background of complex genome-environment interactions. Such genome-environment interactions frequently activate epigenetic mechanisms that add an additional layer of control to the genome and provide cells with a mechanism by which transient stimuli can be transformed into long-term adaptive changes. Epigenetic control of gene expression has been intensively studied in proliferating cells, e.g. in the field of stem cell biology, during developmental processes, and in cancer. However, comparatively less is known on the role of epigenetic regulation in post-mitotic cells.

Our group studies the role of epigenetic and epi-transcriptomic control of gene transcription in cardiomyocytes and neurons. Published and preliminary finding show that histone-methylation as well as RNA-methylation is severely de-regulated at the onset of heart and brain disease. The PhD student will study m6A RNA-methylation and H3K4 methylation in the healthy and diseases heart using cardiomyocyte specific knockout mice of H3K4 methyltransferases and demethylases as well as corresponding mouse and human cellular models.

• Berulava, T., Buchholz, E., Elerdashvili, V., Pena, T., Islam, M. R., Lbik, D., Mohamed, B. A., Renner, A., von Lewinski, D., Sacherer, M., Bohnsack, K. E., Bohnsack, M. T., Jain, G., Capece, V., Cleve, N., Burkhardt, S., Hasenfuss, G., Fischer, A., & Toischer, K. (2020). Changes in m6A RNA methylation contribute to heart failure progression by modulating translation. European journal of heart failure, 22(1), 54–66. https://doi.org/10.1002/ejhf.1672
  
  
• Benito E, Kerimoglu C, Ramachandran B, Pena-Centeno T, Jain G, Stilling RM, Islam MR, Capece V, Zhou Q, Edbauer D, Dean C, Fischer A. RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after Environmental Enrichment. Cell Reports. 2018 Apr 10;23(2):546-554.
  
  
• Kerimoglu C, Sadman SM, Jain G, Benito E, Burkhardt S, Capece V, Kaurani L, Halder R,, Agís-Balboa RC, Stilling R, Urbanke U, Kranz A, Stewart AF, Fischer A. Kmt2a and kmt2b mediate memory function by affecting distinct genomic regions. Cell Reports, (2017) 20, 3: 538-548
  
  
• Bahari-Javan, S., Varbanov, H., Halder, R., Benito, E., Kaurani, L. Burkhardt, S. Anderson-Schmidt, H. Anghelescu, I. Budde, M. Stilling,R.M., Costa, J. Dietrich D., Figge, C., Folkerts, H., Gade, K., Heilbronner, U., Koller, M. Konrad, C., Nussbeck, S.Y., Scherk, H., Spitze, C., Stierl, S., Stöckel, J. Thiel, J. Hagen, M., Zimmermann, J., Zitzelsberger, A., Schulz, A., Schmitt, A., Delalls, I., Falkai, P., Schulze, T.G. Dityatev, A., Sananbenesi, F., Fischer, A. Hdac1 as a target for individualized therapy of schizophrenia patients. PNAS, 2017. 114(23):E4686-E469
  
  
• Agís-Balboa, R.C., Pinhero, P., Rebola, N. Kerimoglu, C., Benito, E., Gertig, M., Bahari-Javan, S. Jain, G. Burkhardt, S. Delalle, I. Jatzko, A., Dettenhofer, M., Zunszain, P.A. Schmitt, A., Falkai, P. Pape, J., Binder, E.B., Mulle, C. Fischer, A.*, Sananbenesi, F. Formin 2 links Neuropsychiatric Phenotypes at Young Age to an increased Risk for Dementia. EMBO J (2017) 36(19):2815-2828* shared last author
  
  
• Halder R, Hennion M, Vidal RO, Shomroni O, Rahman RU, Rajput A, Centeno TP, van Bebber F, Capece V, Vizcaino JC, Schuetz AL, Burkhardt S, Benito E, Sala MN, Javan SB, Haass C, Schmid B, Fischer A*, Bonn S. DNA methylation changes in plasticity genes accompany the formation and maintenance of memory. Nat Neurosci. 2016 Jan;19(1)* shared last author
  
  
• Benito, E. Urbanke, U., Ramachandran, B., Barth, J. Halder, R., Awasthi, A. Jain, G., Capece, V., Burkhardt, S., Navarro-Sala, M. Nagarajan, N, Schütz, AL., Johnsen, SA. Bonn, SA Lührmann, R., Dean, C., Fischer, A. Reinstating transcriptome plasticity and memory function in models for cognitive decline. Journal of Clinical Investigation, (2015) 125(9):3572-84
  
  
• Fischer, A. Epigenetic Memory: The lamarckian brain, EMBO J. 2014 2;33(9):945-67