Neurohomeostasis

Management

BIH Visiting Professor, funded by Stiftung Charité
https://orcid.org/0000-0002-4265-3398

Research Interest

Welcome to the Neurohomeostasis Lab, where we harness a dynamic, multidisciplinary and translational approach, integrating cell culture, protein biochemistry, imaging, ex vivo pharmacology, and cutting-edge multi-omics techniques.
Our mission! To uncover the intricate mechanistic links between glucocorticoid-mediated stress and its impact on proteostasis and cognition, traversing the spectrum from health to disease. The Neurohomeostasis Lab also spearheads several pre-clinical and clinical studies to not only contextualize our findings but also to identify promising therapeutic targets for the treatment of neuropsychiatric disorders in animal models and humans.
Our lab is dedicated to unraveling the complexities of autophagy and its interplay with stress, with a particular focus on the role of FKBP51, a versatile protein that plays a crucial role in stress response pathways with strong links to metabolism, immune responses and autophagy. This exploration stands at the intersection of cellular health and the body's response to (environmental/psychological) stressors, providing profound insights into the maintenance of proteostasis and metabolic equilibrium.

Projects

In multiple interdisciplinary projects, the Neurohomeostasis Research Group has aimed to incorporate the crucial central interplay between stress and the maintained equilibrium of homeostatic processes as part of a holistic translational research concept. The core projects of the research group can be summarized into three interconnected project branches:

The influence of stress on autophagy in conjunction with cellular and systemic processes such as metabolism and immune responses: Autophagy, a cellular degradation and recycling process, is central to our investigations. It serves as a critical mechanism for the removal of damaged proteins and organelles, thus maintaining cellular integrity. Our research examines how stress influences autophagy, specifically through the modulation of FKBP51. This interaction provides a window into the body's adaptive responses to stress, presenting potential therapeutic avenues for enhancing cellular resilience. Extending our inquiry to the realm of virology, we explore the dynamic relationship between autophagy and viral infections. This pivotal line of research elucidates autophagy's role as a defense mechanism against viral invasions. Understanding these processes offers novel perspectives for antiviral strategies and therapeutic interventions. Another powerful factor that is closely related to both immune-metabolic factors and stress-induced mechanisms is the immune response and its crosstalk with neuroplasticity and neurochemistry. Here my laboratory describes fundamental new findings in the area of stress-induced cytokine responses to chronic stress in neural immune cells (microglia) and in the defense against viruses. We founded the concept of secretory autophagy in brain cells. In this process, molecules to be recycled, such as cytokines and proteases, are not broken down as usually in canonical autophagy, but are channeled out of the cell. This can lead to inflammasome formation and massive (neuro-)inflammation.
Exploration and application of novel target structures for therapeutic approaches and new intervention strategies:
Our research not only advances the boundaries of scientific knowledge but also holds the promise of developing novel therapeutic strategies that could transform the landscape of healthcare and disease management. Through our dedicated efforts and collaborative spirit, we strive to contribute to a healthier future.
Autophagy stands at the forefront of our research as a promising target for therapeutic intervention. By dissecting the signaling pathways associated with this homeostatic process, we aim to unlock new therapeutic strategies for managing stress-related conditions. The compound spermidine has emerged as a focal point in our research due to its capacity to induce autophagy. Investigating spermidine and its therapeutic potential is not only of scientific interest but also holds promise for translational medicine, potentially ushering in new treatments that harness the power of autophagy to combat disease and promote longevity.
Human intervention studies for the systemic exploration and translation of stress, depression, and autophagy.
The translation of our research findings into human intervention experiments is a particular focus of our research group. In our interdisciplinary team, consisting of highly trained clinician scientists and basic researchers, we have developed experimental pipelines to assess the influence of various stressors on multiple molecular parameters in innovative experiments.
Conceptual advance. While there is ample evidence of a central function of autophagy in mediating stress responses at the cellular level and directly affecting brain function and mental health, there is a paucity of research addressing causal relationships between stressors, autophagy and brain function in vivo. Leveraging a bottom-up approach that combines mechanism-driven neuroscience, clinical studies in patients and healthy subjects, targeted and untargeted biomarker identification and innovative technologies, our research will uncover the mechanisms underlying stress-environment interaction with neurobiology and identify ground-braking solutions to promote brain function and stress resilience. Importantly, by including an age- and gender-balanced design in our pre-clinical and clinical studies we optimize translation and results will be applicable to deliver innovative, readily applicable and effective strategies for comprehensive prevention and treatment of problems of mental health and cognitive function across the population. Together, the results of our research will unlock the full potential and effective use of biomedical research for the development of health-promoting interventions.
In order to understand the effect of stress and other environmental factors such as exercise, targeted diets or high stress on these processes, intervention experiments are carried out in our research group with healthy volunteers and/or moderately depressed patients; see also registered studies at ClinicalTrials.gov Fasting study NCT04739852 (AutoFast); Autophagy Intervention Study in Depression Patients NCT04823806 (StressLess); Stress-response study in healthy volunteers NCT05144022 (HighStress) and Exercise-Autophagy crosstalk study NCT05359744. Employing an array of advanced analytical techniques - including metabolomics, proteomics, phospho-proteomics, and transcriptomics - we endeavor to link our findings directly to the processes of metabolism and proteostasis.

Methoden

In the AG Neurohomeostasis, we primarily employ molecular, biochemical, and cell biological methods to address our specific research questions. This involves using targeted techniques (e.g., Western Blotting, qPCR, ELISA) and Omic methods (Phospho-/Proteomics, Metabolomics, Transcriptomics), tailored to each project and underlying scientific inquiry. This comprehensive methodology not only enriches our understanding of cellular function under stress but also illuminates the pathways through which cells achieve homeostasis.

In our interdisciplinary, highly translational projects, we utilize common rating scales, questionnaires, and neuropsychological tests commonly used in psychiatric research, as well as wearables for collecting additional physiological parameters. A central aspect of our translational studies is the molecular biological processing of blood samples from participants or patients. Here, we employ tailored and targeted ex vivo stimulation protocols to test, for example, metabolic or immunological responses.

Team

Core Team:

Thomas Bajaj (PhD student)
Dr. Tim Ebert (PostDoc / Clinician Scientist, Neuro-aCSis Grantee)
Dr. Sarah Mackert (PhD student / Clinician Scientist, Neuro-aCSis Grantee)
Yara Mecdad (PhD student)
Dr. Christine Niemeyer (PostDoc / Clinician Scientist)
Dr. Clara Sokn (PostDoc, DAAD stipend)
Djordje Stanivuk (PhD student / shared with Uni Mainz)
Katja Wirtz (Lab Management)
Ellen Junglas (Lab Management)

Students:

Maria Jesus Alcantara (MSc Neuroscience)
Elena Bonilla (MSc Neuroscience)
Marieke Brockherde (MSc Neuroscience)
Lily Aline Heckmann (MD student)
Maren Jasper (MD student)
Valerie Kempf (MD student)
Marcel Laakmann (MD student)
Katharina Lammertz (MD student)
Klaudius Prominski (BSc Neuroscience (Köln))
Nathalie Rieder (MSc Neuroscience)
Jonathan Strupp (MD student)
Ebru Tuncöz (MD student)

Collaborations

Collaboration is central to our research philosophy. We proudly cultivate a network of partnerships across national and international borders, embracing a multidisciplinary approach that enriches our research and accelerates discovery. These collaborations are instrumental in tackling the multifaceted questions of biology, demonstrating the power of collective scientific endeavor.

Alon Chen (Weizman Institute of Science, Rehovot, Israel)
Jürgen Cox (Max Planck Institut für Biochemie, Martinsried)
Jakob Hartmann & Kerry J. Ressler (McLean Hospital, Harvard Medical School, Boston US)
Bernhard Kuster (Technische Universität, München)
Frank Madeo & Tobias Eisenberg (Universität Graz, Graz, Austria)
Felix Meissner (Uniklinikum Bonn, Bonn)
Marcel A. Müller (Institut für Virologie, Charité, Berlin)
Marianne B. Müller (Leibnitz Institut für Resilienz Forschung, Universitätsklinik Mainz, Mainz)
Mathias V. Schmidt (Max Planck Institut für Psychiatrie, München)
Valentin Stein & Anne Gellner (Uniklinikum Bonn)
Jens Stepan (Technische Universität, München)

Publications

Gassen, N. C., Hartmann, J., Zschocke, J., Stepan, J., Hafner, K., Zellner, A., Kirmeier, T., Kollmannsberger, L., Wagner, K. V., Dedic, N., Balsevich, G., Deussing, J. M., Kloiber, S., Lucae, S., Holsboer, F., Eder, M., Uhr, M., Ising, M., Schmidt, M. V., & Rein, T. (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.
Gassen, N. C., Fries, G. R., Zannas, A. S., Hartmann, J., Zschocke, J., Hafner, K., Carrillo-Roa, T., Steinbacher, J., Preißinger, S. N., Hoeijmakers, L., Knop, M., Weber, F., Kloiber, S., Lucae, S., Chrousos, G. P., Carell, T., Ising, M., Binder, E. B., Schmidt, M. V., Rüegg, J., Rein, T. (2015). Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine. Science Signaling, 8(404), ra119.
Gassen, N. C., Hartmann, J., Zannas, A. S., Kretzschmar, A., Zschocke, J., Maccarrone, G., Hafner, K., Zellner, A., Kollmannsberger, L. K., Wagner, K. V., Mehta, D., Kloiber, S., Turck, C. W., Lucae, S., Chrousos, G. P., Holsboer, F., Binder, E. B., Ising, M., Schmidt, M. V., & Rein, T. (2016). FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications. Molecular Psychiatry, 21(2), 277–289.
Zannas, A. S., Jia, M., Hafner, K., Baumert, J., Wiechmann, T., Pape, J. C., Arloth, J., Ködel, M., Martinelli, S., Roitman, M., Röh, S., Haehle, A., Emeny, R. T., Iurato, S., Carrillo-Roa, T., Lahti, J., Räikkönen, K., Eriksson, J. G., Drake, A. J., Waldenberger, M., Wahl, S., Kunze, S., Lucae, S., Bradley, B., Gieger, C., Hausch, F., Smith, A.K., Ressler, K.J., Müller-Myhsok, B., Ladwig, K.H., Rein, T., Gassen, N. C., Binder, E. B. (2019). Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB–driven inflammation and cardiovascular risk. Proceedings of the National Academy of Sciences, 116(23), 11370–11379.
Pubmed-Liste: Nils Gassen

Funding

MetaStress (DFG) – collaboration with MV Schmidt (MPI Psychiatry)
ASTROMICS (WEAVE/ DFG) – collaboration with MV Schmidt (MPI Psychiatry), M Slezak (PORT, Wroclaw)
ProteoCoV (BMBF) – collaboration with MA Müller (Charité, Berlin)
STEROID (Stiftung Charité, funded by Johanna Quant) – collaboration with MA Müller (Charité, Berlin)
ProGReS (DFG) – collaboration with MA Müller (Charité, Berlin)
Autophagy Inducers (Brain&Behaviour Research Foundation, Max-Planck Society, KAHN-I Fund) – collaboration with MPI Psychiatry & LDC Dortmund
AMPAR Inducers (Max-Planck Society, KAHN-I Fund) – collaboration with MPI Psychiatry & LDC Dortmund
ProATTaC (Volkswagen Foundation) – collaboration with MA Müller (Charité, Berlin), Jakob Trimpert (FU Berlin), LDC Dortmund
AutoResilience (DFG) – collaboration with MV Schmidt (MPI Psychiatry)
PROGRESS (Era-Net Neuron/ DFG) – collaboration with MB Müller (Mainz), J Bohacek (Zurich), Helena Sork (Tartu), Iris Hovatta (Helsinki)
Neuro-aCSis Stipend (2023) – awarded to Tim Ebert
Neuro-aCSis Stipend (2024) – awarded to Sarah Mackert
AutoFast – NCT04739852 – collaboration with A Michalsen (Charité Berlin)
HighStress – NCT05144022
StressLess – NCT04823806 – collaboration with F Madeo (Graz) & Guido Kroemer (Paris)
AutoSport – NCT05359744 – collaboration with J Stepan (Salzburg)
NutriMol – NCT06016530

Contact

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

Open Positions:

Students from the fields of molecular biology, biochemistry, pharmacology, or neuroscience have the opportunity to work on projects for their MSc, Dr. rer nat., or Dr. med. as part of the research group.