Neurohomeostasis

Management

Dr. rer. nat. Nils Gassen

Translational Research of Protein Quality Control Associated with Mental Disorders

A large part of today's translational research and thus also a large part of the knowledge gained so far from this branch of research is concerned with the study of gene regulation and gene synthesis, i.e. with the construction of biological units. However, currently only a small part of research focuses on the underlying mechanisms that are essential for the degradation or maintenance of the synthesized genes and proteins.

In the research group of Neurohomeostasis, we are concerned with the research of molecular biological and cell biological mechanisms that are important for maintaining the balance between the building up and degradation processes in the cell.

Aims of the Research Group

The research group has set itself the task of including the important and central process for maintaining the molecular balance of the cell as part of translational, neurobiological research in the field of psychiatry. Therefore, one of the core goals of the RG is, in close cooperation with psychiatrists and psychologists, to establish a causal connection between the observations resulting from the clinic and molecular biological and cellular processes. The knowledge gained will also be used to develop more targeted diagnoses and tailored therapies. In this way, questions from the clinic and biomarker studies are recorded, corresponding working models are created and hypothesis-driven molecular biological, biochemical, cellular and functional research is carried out.
The focus of this interdisciplinary group is the search and research of mechanisms that are relevant for the maintenance of neuronal and synaptic homeostasis. This includes various cellular processes:

1. autophagy (selective and non-selective autophagy),
2. lysosomal degradation mechanisms,
3. proteasomal degradation,
4. molecular chaperones,
5. DNA damage response.

With interdisciplinary project approaches and a wide range of methods, we answer psychiatric questions in order to decipher cellular processes in physiology and pathophysiology. The following clinical pictures are of particular interest:

1. Stress-associated diseases (depression, anxiety, trauma),
2. attention deficit hyperactivity disorder (ADHD),
3. psychopharmacology,
4. alternative therapy options (ECT, VNS, sports, nutrition/diets) and
5. in particular comorbidities with links to other fields like metabolism, immune system, pathogen defense.

Ongoing projects with established collaboration partners such as the LDC in Dortmund, the Max Planck Institute for Psychiatry Munich and the Charité Berlin allow us to bring research findings back to the clinic, which corresponds to the guiding principle of translational research.

Ongoing Projects

The research group focuses in particular on the research of proteostasis (protein homeostasis) of neuro-psychiatric relevant proteins and organelles. We investigate the role of psychiatric diseases on the various selective and non-selective mechanisms for protein degradation.

Another strong project branch is psychopharmacology:

1. The influence of common psychopharmaceuticals on cellular mechanism for protein quality control is examined.
2. Novel strategies for pharmacological therapeutic approaches are gained and developed through newly acquired knowledge.

Education

Students from the fields of molecular biology, biochemistry, pharmacology or the neurosciences have the opportunity to work on the MSc, Dr. rer nat. or Dr. med. projects.

Research Group Leader

Dr. rer. nat. Nils Gassen

Klinik und Poliklinik für Psychiatrie und Psychotherapie
Universitätsklinikum Bonn AöR
Venusberg Campus 1
53127 Bonn
Tel.: +49 228 287-15793

Team

Dr. Elmira Anderzhanova, MD, Staff Scientist

Thomas Bajaj, PhD Student

Tim Ebert, PostDoc

Martina Lennarz, TA

Dr. Christine Niemeyer, PostDoc

Dr. Dr. Jens Stepan, Guest Scientist
(Uniklinikum Salzburg)

Daniel Heinz, Guest Scientist
(Max-Planck Institute of Psychiatry, Munich)

Katharina Lammerz, MD Student

Ebru Tuncöz, MD Student

Selected Publications

• Gassen NC, Niemeyer D, Muth D, et al. (2019) SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nature Communications 18;10(1):5770.
• Zannas, AS, ... , Gassen, NC and Binder, EB (2019). Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB–driven inflammation and cardiovascular risk. Proc. Natl. Acad. Sci. 116, 11370–11379.
• Balsevich G, … , Gassen NC* and Schmidt MV* (*joint senior authors) (2017) Stress-responsive FKBP51 is a novel regulator of metabolic function and Akt2-AS160 signaling Nature Communications  8(1):1725.
• Gassen NC, Hartmann J, Zannas AS et al. (2016) FKBP51 inhibits GSK3b and augments the effects of distinct psychotropic medications. Molecular Psychiatry 21(2):277-89
• Gassen NC, Fries GR, Zannas AS, et al. (2015) Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of antidepressant paroxetine. Science Signaling  8(404):ra119
• Gassen NC, Hartmann J, Schmidt MV, et al. (2015) FKBP5/FKBP51 Enhances Autophagy to Synergize with Antidepressant Action. Autophagy 11(3):578-80
• Gassen NC, Hartmann J, Zschoke J et al. (2014) Association of FKBP51 with priming of autophagy pathways and mediation of antidepressant treatment response: evidence in cells, mice, and humans. Plos Medicine  11(11):e1001755