Epigenetics and Systems Medicine in Neurodegenerative Diseases
Prof. Dr. André Fischer
Group Leader and Site Speaker
Von-Siebold-Str. 3a
37075 Göttingen

andre.fischer@dzne.de
 +49 551 39-61211

Areas of investigation/research focus

The long-term goal of our research is to understand the cellular and molecular mechanisms underlying brain diseases and to develop neuroprotective and neuroregenerative therapeutic approaches. To understand the pathogenesis of Alzheimer’s disease (AD) and to identify effective therapeutic strategies is a major focus.

There is now accumulating evidence that on an individual level health or disease critically depends on the interaction between genes and environment. Epigenetic mechanisms such as histone-modification, DNA-methylation and non-coding RNA-mediated processes are key-regulators of gene-environment interactions. Importantly, such epigenetic mechanisms have recently been implicated with the pathogenesis of neurodegenerative and psychiatric diseases.

 more Infos

Thus our current hypothesis is that deregulation of genome-environment interactions, especially via epigenetic gene-expression, is a key feature of neurodegenerative diseases such as Alzheimer’s disease.

One immediate aim is to analyze genetic and environmental risk factors for Alzheimer’s diseases with respect to epigenetic gene-expression. We propose that a combination of those factors may lead to a disease-specific epigenetic signature that contributes to the pathogenesis and would therefore be a suitable drug target.

Our aim is to define combinatorial maps of epigenetic-modifications during disease progression and therapeutic intervention. This data will be combined with the analysis of the corresponding key-enzymes of epigenetic gene-expression. Our mechanistic approaches involve genetic and pharmacological means to investigate how individual chromatin-modifying enzymes affect neuronal plasticity, synaptic function and learning & memory in the young, aging and diseased brain.

Schlüsselpublikationen

Kerimoglu C, Sakib MS, Jain G, Benito E, Burkhardt S, …, Fischer A. Kmt2a and Kmt2b mediate memory function by affecting distinct genomic regions. Cell Rep. 2017 Jan 01; 20:538-48. doi: 10.1016/j.celrep.2017.06.072
Bahari-Javan S, Varbanov H, Halder R, Benito E, Kaurani L, …, Fischer A. HDAC1 links early life stress to schizophrenia-like phenotypes. Proc Natl Acad Sci USA. 2017 Jan 01; 114:E4686-E4694. doi: 10.1073/pnas.1613842114
Eva Benito, Hendrik Urbanke, Binu Ramachandran, Jonas Barth, Rashi Halder, Ankit Awasthi, Gaurav Jain, Vincenzo Capece, Susanne Burkhardt, Magdalena Navarro-Sala, Sankari Nagarajan, Anna-Lena Schötz, Steven A. Johnsen, Stefan Bonn, Reinhardt Löhrmann, Camin Dean, André Fischer. HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models. Journal of Clinical Investigation. 2014 Dec 31; 125:3572-3584. doi: 10.1172/JCI79942
Peleg S, Sananbanesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, …, Fischer, A. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science. 2010 Jan 01; 328:753-6. doi: 10.1126/science.1186088
Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. Recovery of learning and memory is associated with chromatin remodeling. Nature. 2007 Jan 01; 447:178-82.

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