Forschung

Main research interests

Our research group is interested in identifying the molecular mechanisms involved in the development of mental disorders, particularly those with an onset in adolescence and early adulthood (i.e. affectice disorders, schizophrenia, and ADHD). Our main focus are the synaptic mechanisms of the glutamatergic synapse with a particular interest on proteins and protein-protein interactions. The main target here is the protein network encompassing AMPA and NMDA receptors, their auxiliary subunits, as well as neuronal nitric oxide synthase (NOS-I) and its adapter protein (NOS1AP) and their interaction partners. In addition, we investigate the effect of environmental factors (e.g. stress, inflammation) on these molecular targets, and how environmental and genetic factors interact to cause psychiatric disorders. By targeting these pathways, genetically and pharmacologically, we aim to identify the aetiology as well as novel treatment opportunities for these disorders.

To investigate these mechanisms, we utilize a wide range of methods, including behavioural and molecular phenotyping of mice, cell culture models, in vitro and in vivo viral gene transfer, morphological and histological analyses, as well as the genetic and molecular investigation of human biosamples. 

Watch this Instagram Reel from the Goethe University Career Service showing the average day in the life of our very own Melike Aydin (BSc student in 2023)

 

Selection of current projects:

1. Assessing the role of AMPA receptors and their auxiliary subunits in cognition and depression-like phenotypes using using a translational approach in mice, human and murine cell cultures and in human subjects.
2. Investigation of lipids, lipid metabolites and lipid signalling in mental disorders (collaboration with Irmgard Tegeder)
3. Viral vector-mediated interrogation of the endocannabinoid system in plasticity and cognition in relation to PTSD (collaboration with Sabrina Lisboa, University of São Paulo)

Former members

• Esin Candemir (PhD student/Postdoc)
• Maja Adel (PhD student, graduated from the University of Barcelona)
• Makoto Kinoshita (Postdoc/guest researcher)
• MD students: Nicole Schenk, Saleha Arshad, Veronika Frerichs, Lea Schöls
• MSc students: Anna Yotova, Jessica Manchen, Evelien Willemijn Burghgraef, Gloria Mico, Tsendmaa Tsengenbayar, Aayush Marishi, Elif Ertas, Johanna Diehl
• BSc students: Anita Kumar, Solmaz Bikas, Julia Henninger, Christina Sauerland, Gwenn Dequatremare, Hannah Wojtzik, Johanna Diehl, Soner Cagun, Leah Luwisch, Melosha Puspathasan, Christian Rische, Harishny Sarma, Melike Aydin, Freya Schroedter, Samanta Fast, Melina Davis, Sara Schneidrowski, Selina Ritter, Ainoa Benitez, Juliane Schwarzwald, Lennard Kahl, Laura Como,
• GREP students: Linette Anyiacha, Anastasia Tzafolia
• Visiting researchers: Nikolai Fattakhov (Immanuel Kant Baltic Federal University), Bruna Santos (Federal University of Health Sciences of Porto Alegre), and Gözde Ayhan (Marmara University), Anna Paula Amorim Marques (University of São Paulo)

 

Collaborations

• Michael Courtney, University of Turku, Finland
• Irmgard Tegeder, Department of Clinical Pharmacology, Goethe University Frankfurt
• Sabrina Lisboa, University of São Paulo, Brazil
• Ioannis Sotiropoulos, National Centre for Scientific Research “Demokritos”, Greece

Funding

• LOEWE Schwerpunkt LipidSpace (2026-2029)
• Studienstifung des deutschend Volkes (PhD scholarships to Maja Adel from 2021-2025 and to Johanna Diehl since 2025)
• Main-Campus Stipendiatenwerk (Stiftung Polytechnische Gesellschaft (stipend to Florian Freudenberg from 2021-2022)
• DAAD (short-term grant to Gözde Ayhan in 2020)
• DFG (Research Grant funding from 2014-2017 & 2017-2019)
• BMBF (DAAD PPP Finland funding scheme from 2017-2019)
• Avicenna Studienwerk (PhD scholarship to Dilhan Esen from 2018-2022).
• JSCNP (Overseas trainees fellowship to Makoto Kinoshita from 2017-2018)
• Russian Ministry of Education (Russian Presidential scholarship to Nikolai Fattakhov from 2016-2017)

Selected Publications

Co-authors from our research group are marked in bold

For a complete list of publications see Google scholar.

• 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, 107918. Advance online publication. https://doi.org/10.1016/j.phrs.2025.107918
• Freudenberg, F., Reif-Leonhard, C., & Reif, A. (2024). Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression. European archives of psychiatry and clinical neuroscience, 10.1007/s00406-024-01875-z. Advance online publication. https://doi.org/10.1007/s00406-024-01875-z
• 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
• Candemir, E., Fattakhov, N., Leary, A. O., Slattery, D. A., Courtney, M. J., Reif, A., & Freudenberg, F. (2023). Disrupting the nNOS/NOS1AP interaction in the medial prefrontal cortex impairs social recognition and spatial working memory in mice. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 67, 66–79. https://doi.org/10.1016/j.euroneuro.2022.11.006
• Esen-Sehir, 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
• 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
• Grünewald, L., Chiocchetti, A. G., Weber, H., Scholz, C. J., Schartner, C., Freudenberg, F., & Reif, A. (2021). Knockdown of the ADHD Candidate Gene Diras2 in Murine Hippocampal Primary Cells. Journal of attention disorders, 25(4), 572–583. https://doi.org/10.1177/1087054718822129
• Esen-Sehir, D., Courtney, M. J., Bittner, R. A., Reif, A., & Freudenberg, F. (2019). Establishing an effective dose for chronic intracerebroventricular administration of clozapine in mice. Acta neuropsychiatrica, 31(6), 305–315. https://doi.org/10.1017/neu.2019.31
• Candemir, E., Kollert, L., Weißflog, L., Geis, M., Müller, A., Post, A. M., O'Leary, A., Harro, J., Reif, A., & Freudenberg, F. (2016). Interaction of NOS1AP with the NOS-I PDZ domain: Implications for schizophrenia-related alterations in dendritic morphology. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 26(4), 741–755. https://doi.org/10.1016/j.euroneuro.2016.01.008
• Freudenberg, F., Alttoa, A., & Reif, A. (2015). Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders. Genes, brain, and behavior, 14(1), 46–63. https://doi.org/10.1111/gbb.12193