I am heading the Nuclear Function Group at DZNE Bonn. The overarching hypothesis (Figure 1) driving our work is that epigenetic barriers insulating cell identity become disrupted during aging and in disease states such as neurodegenerative diseases (NDDs) via loss of the more compact form of chromatin (heterochromatin), in turn affecting tissue homeostasis and contributing to disease pathogenesis and inflammation. In particular, we propose that mechanisms compacting chromatin at retrotransposable elements (RTEs) become dysfunctional during aging (Figure 1), with implications for neuronal function and inflammation. My group focus on a major RTE-silencing complex, the Daxx/histone H3.3 complex, which, as we and others have shown, when mutated drives human brain and bone cancer (3,4). Critically, Daxx protein is downregulated during aging in neurons and innate immune cells, in turn contributing to neuronal dysfunction and inflammation in the brain and the periphery (1, 2, and ongoing/submitted work, see below).

I have been cooperating with several groups within DZNE and elsewhere (see below), and rely on access to PRECISE and Core Research Facilities. Present and future focus is on epigenetic basis of neuro-inflammation during aging and NDD pathogenesis and identification of new targets at chromatin levels that could be exploited therapeutically. In particular, we aim to target key nodes in the RTE life cycle using clinical grade agents, in cooperation with Rayk Behrendt and Hiroki Kato (Uni Bonn).

Finally, I joined DZNE as ERC grant holder and since then have been successful in attracting further third-party funding as program/project grants and individual fellowships to lab members (e.g. Mildred Scheel School of Oncology, Marie Curie). Current funding: DZNE, DLR, German Cancer Aid.

• We implicated RTE repressors in regulation of cell identity during hematopoiesis and in adult microglia, with implications for (neuro)inflammation (2; being revised; Figure 2).
• The Rhineland Study data have been mined to investigate novel associations with RTE expression (in preparation, in collaboration with AG Breteler and AG Aziz).
• We have completed longitudinal analysis of chromatin and transcriptional perturbations across multiple NDD models at bulk and single cell level (first study in preparation; jointly with G Mallucci, Altos).
• We implicated a stress-responsive nuclear structure as key (targetable) player in IFNopathies (in preparation; jointly with H Kato, Uni Bonn).
• As part of work supported by third party funding on cancer (DLR, Wilhelm Sander Stiftung, Mildred Scheel School of Oncology and German Cancer Aid), we are investigating epigenetic perturbations and in vivo behavior of brain cancer cells and immune cells within the tumor microenvironment.