Research Group

Dr. rer. nat. Nils C. Gassen

Group leader

My motivation for research in this field stems from the conviction that stress - one of the most pervasive forces shaping human health - is not merely a cause of disease but a window into the fundamental principles of adaptation. I am driven by the belief that we can change how we understand and treat stress-related disorders by deciphering their cellular and molecular logic, particularly through the lens of autophagy and homeostatic balance. The translational potential of my groups work is unparalleled, bridging basic molecular mechanisms with meaningful clinical applications. Equally motivating is the opportunity to mentor a new generation of creative scientists who think across boundaries and flourish in collaborative, interdisciplinary settings. Together with an outstanding network of colleagues, I strive to redefine how we study, conceptualize, and ultimately transform stress into resilience.

Cellular Homeostasis and Autophagy as a Core Mechanism of Stress and Stress Resilience

This project line centers on autophagy as a fundamental integrator of stress adaptation, connecting molecular mechanisms of proteostasis, metabolism, and resilience. Building on the projects ASTRA and AutoHealth, it explores how autophagy-inducing polyamines (e.g. spermidine) and metabolic regulators in glial and neuronal cells re-establish homeostasis under stress. ASTROMICS adds a complementary focus on astrocyte mitochondrial metabolism, highlighting glial contributions to stress-induced metabolic dysregulation and energy imbalance. The work employs autophagy-reporter models, metabolomics, and in vivo manipulations to dissect the temporal dynamics of autophagic flux under acute and chronic stress, as disease model for depression. Integrating human and animal data, it defines autophagy as a bidirectional communication axis between the brain and peripheral metabolic systems. Through collaboration across molecular, behavioral, and translational domains, this line establishes autophagy as both a molecular hallmark of resilience and a therapeutic target for stress-related and metabolic comorbidities. The goal is to define autophagy as a master regulator of stress adaptation and brain-body homeostasis, establishing a mechanistic basis for targeted interventions that promote resilience and prevent stress-related pathology.

Across the PROGRESS, StressEVs, and MoodTransfer projects, stress is conceptualized as a dynamic, multiscale process linking molecular, physiological, and behavioral dimensions, forming the basis of a systems biology framework of stress and resilience that spans from behavioral dynamics to translational biomarkers. PROGRESS introduces the concept of the “tipping point of stress,” integrating longitudinal, stress-free sampling and machine learning–based behavioral analysis to define molecular signatures that distinguish resilience from vulnerability in a mouse model. StressEVs builds upon this framework by identifying extracellular vesicles (EVs) as carriers of stress-related signals and potential biomarkers bridging central and peripheral stress responses. MoodTransfer complements this systems view by testing the causal transmission of “mood states” through plasma proteomic and metabolomic signatures, representing a paradigm shift in understanding affective disease as a systemic rather than purely cerebral process. Together, these projects form a translational pipeline - from mechanistic animal models to human cohorts - establishing stress biomarkers that are measurable, predictive, and actionable in personalized psychiatry. The goal is to identify and validate integrative molecular and behavioral signatures of resilience and vulnerability, transforming stress research into a predictive and preventive science of mental health.

Funded projects:

• Disease-predisposing or Resilience-promoting? Decoding the Systems Biology and Behavioural Predictors and Determinants of the Tipping Point of Stress (PROGRESS, ERA-NET NEURON)
• Long-term Analysis of Stress-induced Behavioral Dynamics: Extracellular Vesicles as Biomarkers (StressEVs, DFG)
• From Black Bile to Melancholia: Transmission of Mood States via Plasma Transfer (MoodTransfer, Volkswagen Foundation)
• The Polyamine Hypothesis of Resilience: Autophagy-inducing Polyamines in Stress, Stress-related Diseases and Resilience (ASTRA, DFG)
• Autophagy linking Peripheral Metabolism and Stress to Mental Health: From Model Systems to Clinical Application (AutoHealth, ERA-NET NEURON JTC 2024)
• Role of Astrocyte Mitochondrial Metabolism in Chronic Stress (ASTROMICS, DFG Weave)

Viral-metabolic Interface: Glucocorticoid Signaling, Immunometabolism, and Cellular Proteostasis

This line investigates how viral infection acts as a systemic stressor that exploits and disrupts cellular homeostatic mechanisms - particularly glucocorticoid signaling, proteostasis, and autophagy. ProGReS and STEROiD identified the glucocorticoid receptor (GR) as a molecular hub linking psychological and viral stress responses, revealing how SARS-CoV-2 hijacks host autophagy and stress pathways.  ProteoCoV and ProATTaC extend this work toward therapeutic innovation: they characterize autophagy as an antiviral defense mechanism and develop host-directed, autophagy-inducing compounds as broad-spectrum antivirals. This integrative approach - combining molecular virology, proteomics, and pharmacological screening - positions viral infection as a model for allostatic imbalance and resilience collapse. Beyond infection, these findings inform our understanding of how stress hormones and immune signals converge on shared molecular pathways that determine health outcomes under challenge. The goal is to elucidate and therapeutically harness the molecular interface between viral, metabolic, and psychological stress, enabling host-targeted interventions that restore cellular and systemic homeostasis.

Molecular Mediators of Stress Resilience: From Intracellular Sensors to Systemic Adaptation

This line focuses on intracellular sensors and signaling hubs that translate stress exposure into adaptive or maladaptive cellular responses. AutoResilience pioneers the use of Atg9a-targeting nanobodies to modulate autophagy with cell-type precision, offering a novel biotechnological strategy to promote resilience. In parallel, the FKBP-Metabolism project dissects the dual role of the stress co-chaperone FKBP51 as a regulator of glucocorticoid sensitivity and metabolic adaptation. Integrating cellular, molecular, and behavioral analyses, this line explores how FKBP51-driven signaling networks control autophagy, energy balance, and stress recovery across tissues. Together, these efforts define the intracellular mechanisms that couple stress sensing to homeostatic regulation and provide translational entry points for therapeutic modulation. The goal is to unravel and manipulate intracellular signaling networks that determine adaptive capacity, linking molecular stress sensors to organismal resilience and metabolic health.

Funded projects:

• Modulation of Autophagy via Camelid Nanobodies Targeting Transmembranous Atg9a to Selectively Shape Stress Resilience (AutoResilience, DFG)
• The Stress-responsive Psychiatric Risk Factor FKBP51 as a Central Regulator of Metabolic (Dys)function (FKBP-Metabolism, DFG)
• Toward a Theory of Homeostasis under Stress

Toward a Theory of Homeostasis under Stress

Collectively, our three project lines define a coherent, long-term research agenda that unites molecular, cellular, systemic, and translational approaches. They operationalize stress as a measurable deviation from homeostasis and resilience as the active re-establishment of balance. Together, we will position autophagy, glucocorticoid signaling, and systemic metabolism as universal mechanisms of adaptation - across mental health, infection, and physiology - laying the foundation for a transdisciplinary understanding of stress as both threat and opportunity for health.

My career path

Trained as a natural scientist in biochemistry with a focus on molecular biology and cell biology, I have been working in the field of psychiatric research since 2008. During my doctoral and postdoctoral studies at the Max-Planck Institute of Psychiatry in Munich (2008 to 2018), I have gained expertise and experimental knowledge in an interdisciplinary and translational environment in order to work hand in hand with clinicians, psychologists and basic scientists on stress-associated diseases. Since October 2018 I am head of the "Neurohomeostasis" research group at the Clinic and Polyclinic for Psychiatry and Psychotherapy at the University Clinic Bonn. I am leading an interdisciplinary team of basic scientists, electrophysiologists, statisticians and clinicians with the common aim to study the impact of various stressors on brain and systemic function and brain-body interaction. At the beginning of 2023, with the appointment as a Visiting Professor at the Charité in Berlin, I am co-supervising a small research team made up of virologists, immunologists and established stress researchers. In this very productive and outstanding environment, there is exceptionally good interaction between different disciplines in the areas of teaching, research and conception of projects and third-party funding options.

Awards, scholarships, honors:

2012     Mifek Kirschner Award        
2013     Postdoctoral Stipend awarded by the Max-Planck-Society
2016     NARSAD Young Investigator Award, honored by P&S Fund
2023     honored as Berlin Institute of Health / Charité Visiting Professor
             (funded by Stiftung Charité as an initiative of excellence by
             Johanna Quant)