Research

The Molecular Psychiatry Research Group investigates molecular mechanisms of mental disorders, with a focus on synaptic processes, particularly in the glutamatergic system. Using cell culture and mouse models as well as human biosamples, we analyse disease mechanisms and therapeutic targets.

Our research group investigates molecular and synaptic mechanisms of mental disorders, with a particular focus on glutamatergic signalling pathways. Central to our work is the role of AMPA receptors and their auxiliary subunits, such as TARPs, whose regulation we analyse in cell culture and mouse models and target pharmacologically. Closely linked to this, we investigate the molecular mechanisms of rapid-acting antidepressants such as (es)ketamine, with the aim of deriving novel therapeutic approaches, for example through AMPA-positive allosteric modulators. Further glutamatergic and nitrergic targets include nNOS and NOS1AP. In addition, within the LOEWE research cluster LipidSpace, we study lipid spaces and lipid signalling in neuropsychiatric disorders using animal models, cellular systems, and human samples, with a particular interest in extracellular vesicles as carriers of lipid-mediated signals. Complementary projects address the endocannabinoid system at the interface of stress, synaptic plasticity, and behaviour. Methodologically, we combine genetic, molecular, pharmacological, and behavioural approaches with clinically relevant research questions.

• Cell culture models, particularly primary neuronal cultures

• Stress-related and inflammatory mouse models, including behavioural analyses

• Genetic and pharmacological interventions, including AAV-mediated viral gene transfer

• Molecular biological, biochemical, and histological analyses, including qPCR, Western blot, and dendritic morphology analyses

• Lipidomic, metabolomic, and EV-based analyses of human and experimental samples

AMPA receptor remodelling in rapid-acting antidepressant treatment

This project investigates how repeated treatment with glutamatergic rapid-acting antidepressants such as ketamine induces AMPA receptor remodelling and TARP-dependent synaptic adaptations. The aim is to understand mechanisms of sustained response and derive new AMPA-based therapies.

Lipid signalling and extracellular vesicles in neuropsychiatric disorders

This project investigates lipid spaces and lipid-mediated signalling pathways in neuropsychiatric disorders using cellular and mouse models as well as human samples. The focus is on extracellular vesicles as carriers of disease-relevant lipid signals.

Project Duration: 2026–2029

Cooperations: LipidSpace Konsortium, insbesondere Prof. Dr. Irmgard Tegeder und Marco Sisignano

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Endocannabinoid system, stress processing, and synaptic plasticity

This project investigates how the endocannabinoid system regulates stress-related behavioural changes, fear extinction, and synaptic plasticity. The focus is on CB1-, TRPV1-, and FAAH-dependent mechanisms analysed using AAV-based tools in cell and mouse models.

Cooperations: Sabrina Lisboa (University of São Paulo, Brazil)

NOS1AP/nNOS signalling: from genetic risk to synaptic function

This project investigates NOS1AP/nNOS signalling as a glutamate-associated mechanism in psychiatric disorders. It links human genetics and clinical phenotypes with cell and mouse models to translationally assess effects on synaptic plasticity, cognition, and behaviour.

Cooperations: Dr. Michael Courtney (University of Turku, Finland)

Research Funding

• LipidSpace – Zeitlich und räumlich aufgelöste Regulation der Gewebehomöostase durch Lipide in der Mikro- und Nanoumgebung; LOEWE-Schwerpunkt, HMWK; PI in Projekt P9; 2026–2029

• A translational approach to study the interaction of NOS-I and NOS1AP in schizophrenia; DFG Sachbeihilfe, FR 3420/2-2; 2017–2019

• Targeting schizophrenia-related phenotypes using small molecules; Projektbezogener Personenaustausch Finnland, DAAD/BMBF; 2017–2019

• Region-specific control of NOS-I PDZ-interaction: implications in animal models of schizophrenia; DFG Sachbeihilfe, FR 3420/2-1; 2014–2017

Scholarships

• Johanna Diehl; Promotionsstipendium der Studienstiftung des deutschen Volkes; 2025–2029

• Lina Schäfer; FPF-Promotionsstipendium, Fachbereich Medizin, Goethe-Universität Frankfurt; 2022

• Jan Steinheimer; FPF-Promotionsstipendium, Fachbereich Medizin, Goethe-Universität Frankfurt; 2022

• Maja Adel; Promotionsstipendium der Studienstiftung des deutschen Volkes; 2021–2024

• Anna Yotova; Main-Campus-doctus PhD-Stipendium, Main-Campus-Stipendiatenwerk der Stiftung Polytechnische Gesellschaft; 2019–2022

• Dilhan Esen; Avicenna PhD-Stipendium, Avicenna-Studienwerk; 2018–2022

• Makoto Kinoshita; Overseas Trainees Fellowship, Japanese Society of Clinical Neuropsychopharmacology; 2017–2018

• Nikolai Fattakhov; Russian Presidential Scholarship, Russian Ministry of Education; 2016–2017

[Translate to Englisch:] • Johanna Diehl – PhD thesis, Biological Sciences
 Title: Translational analysis of the metabolome and lipidome in relation to environmental and genetic influences in mental disorders
 Supervisor: Florian Freudenberg
 Project assignment: LipidSpace / lipidomics / metabolomics / translational models of mental disorders

• Anisia Barros – Guest PhD student
 Title: The use of genetic tools to investigate TRPV1-mediated neuroinflammatory mechanisms in an Alzheimer’s disease model
 Supervisors: Florian Freudenberg / Sabrina de Souza Lisboa
 Project assignment: Endocannabinoid system / TRPV1 / neuroinflammation / AAV-based tools

• Dilhan Esen – PhD thesis, external
 Title: A translational approach to study the interaction of NOS-I and NOS1AP in schizophrenia
 Supervisor: Florian Freudenberg
 Project assignment: NOS1AP/nNOS signalling / human genetics / translational psychiatry

• Panagiota Pelekanos – MD thesis
 Title: The influence of fatty acid amide hydrolase on morphological and molecular alterations related to post-traumatic stress disorder: studies in a murine cell culture model
 Supervisor: Florian Freudenberg
 Project assignment: Endocannabinoid system / FAAH / PTSD-related mechanisms / cell culture models

• Emre Can Erol – Master’s thesis, PBioC
 Title: Maternal separation and behavioural analysis in juvenile and adult C57BL/6J mice and sex-specific effects of early-life stress on autophagy in the hippocampus and prefrontal cortex
 Supervisor: Florian Freudenberg
 Project assignment: Early-life stress / maternal separation / behaviour / autophagy

• Sarosh Vachha – Master’s thesis, University of Würzburg
 Title: Bioinformatic analysis of NOS1AP in mental illness and its biological context in the brain
 Supervisor: Florian Freudenberg
 Project assignment: NOS1AP / human genetics / bioinformatics / translational psychiatry

• Melina Davis – Master’s thesis, INS
 Title: Dose optimisation and molecular effects of repeated esketamine administration in a mouse model of affective disorder-related phenotypes
 Supervisor: Florian Freudenberg
 Project assignment: Rapid-acting antidepressants / esketamine / AMPA receptor-associated mechanisms

• Zeynep Altay – Master’s thesis, INS
 Title: Optimisation of Poly(I:C)-induced inflammatory activation and analysis of lipidomic and metabolomic alterations in a translational mouse model of neuropsychiatric disorders
 Supervisor: Florian Freudenberg
 Project assignment: LipidSpace / Poly(I:C) model / inflammation / lipidomics / metabolomics

1. Schillo, S. E., Schiweck, C., Aichholzer, M., Yotova, A. Y., Tsengenbayar, T., Edwin Thanarajah, S., Reif, A., & Freudenberg, F. (2025). Hyperresponsiveness to inflammatory stimulation in human neuronal-like cells from patients with inflammation-associated depression. Frontiers in psychiatry, 16, 1576880. https://doi.org/10.3389/fpsyt.2025.1576880 

2. Freudenberg, F., Reif-Leonhard, C., Dawson, G. R., McKernan, R. M., & Reif, A. (2025). All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants. Pharmacological research, 220, 107918. https://doi.org/10.1016/j.phrs.2025.107918 

3. Yotova, A. Y., Li, L. L., O'Leary, A., Tegeder, I., Reif, A., Courtney, M. J., Slattery, D. A., & Freudenberg, F. (2024). Synaptic proteome perturbations after maternal immune activation: Identification of embryonic and adult hippocampal changes. Brain, behavior, and immunity, 121, 351–364. https://doi.org/10.1016/j.bbi.2024.07.040 

4. Esen, D., Kopf, J., Hägele, S., Plichta, M. M., Reif, A., & Freudenberg, F. (2022). Influence of NOS1AP Risk Variants on the Corrected QT (QTc) Interval in the Pharmacotherapy of Schizophrenia. Pharmacopsychiatry, 55(5), 266–273. https://doi.org/10.1055/a-1811-7241 

5. Freudenberg, F., Candemir, E., Chen, X., Li, L. L., Esen-Sehir, D., Schenk, N., Kinoshita, M., Grünewald, L., Frerichs, V., Fattakhov, N., Manchen, J., Bikas, S., Kumar, A., OLeary, A., Slattery, D. A., von Engelhardt, J., Courtney, M. J., & Reif, A. (2021). Hippocampal overexpression of NOS1AP promotes endophenotypes related to mental disorders. EBioMedicine, 71, 103565. https://doi.org/10.1016/j.ebiom.2021.103565 

Full list: Google Scholar.

• ICNF
• Orcid Florian Freudenberg
• Research Gate Florian Freudenberg
• Web of Science Florian Freudenberg
• Zotero

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