The three research groups with the Institute of Pharmacology and Toxicology – Receptor Pharmacology, Neuro Pharmacology, and Molecular Pharmacology – focus on the investigation of function and regulation of heptahelical receptors. The institute is involved with teaching students of medicine, molecular medicine, dentistry, pharmacy, clinical pharmacy and chemistry. In 2020 a laser scanning microscope AXIO LSM 900 was purchased with the support of the State of Thuringia.

Prof. Dr. Stefan Schulz
Drackendorfer Straße 1, 07747 Jena

Institute of Pharmacology and Toxicology

Research projects

Role of chemokines in olfactory neurogenesis

Principle investigator: Prof. Dr. Eva-Maria Neuhaus
DFG 2017 - 2020

Im Gehirn eines adulten Säugetiers findet Neurogenese nur in geringem Umfang statt, das olfaktorische Epithel zeichnet sich dagegen durch hohe Regenerationsfähigkeit aus, die das ganze Leben hindurch erhalten bleibt. Durch gezielte Kombination von genetischen, pharmakologischen, anatomischen und physiologischen Ansätzen untersuchen wir die Rolle von CXCL12 und dessen Rezeptoren bei Regenrationsvorgängen in den sensorischen Neuronen des olfaktorischen Epithels der Maus.

Regulation of opioid tolerance by agonist-selective phosphorylation of endogenous γ-opioid receptors in vivo

Principle investigator: Prof. Dr. Stefan Schulz
DFG 2016-2019

The clinical benefit of morphine and other opioid analgesics in the treatment of chronic pain is limited by the rapid development of tolerance and dependence. The objective of this project is to elucidate the function of C-terminal phosphorylation in the development of opioid tolerance using phosphorylation-deficient MOR knockin mice.

Press release

Genetic dissection of arrestin-mediated µ-opioid receptor signaling in vivo

Principle investigator: Prof. Dr. Stefan Schulz
DFG 2017 - 2020

There are indications for receptors that intracellular signals can be mediated via G proteins as well as via arrestins. These results led to the hypothesis that opioid analgesia is exclusively mediated via G proteins, while respiratory depression and constipation are primarily mediated via arrestin-dependent signaling pathways. In the project, a genetic approach is used to investigate μ-opioid receptor-mediated effects under arrestin-free conditions.

Assessment of the monocyte-dependent immune response to experimental stroke

Principle investigator: Prof. Dr. Ralf Stumm
DFG 2017 - 2021

Monocyte-derived and tissue-resident macrophages are ontogenetically distinct components of the innate immune system. These cells change during inflammation, which complicates assessment of their respective roles in pathology. We found that Cxcr4 is expressed in the hematopoietic stem cell lineage, but absent in microglia and other tissue-resident macrophages. Using Cxcr4-CreER(T2) for conditional time-specific gene targeting, we dissect spatio-temporal responses of monocytes and microglia after stroke.

Press release

Regulation of Interneuron Migration by CXCR4 and CXCR7

Principle investigator: Prof. Dr. Ralf Stumm
DFG 2016 - 2024

GABAergic interneurons of the cerebral cortex originate in the ventral telencephalon. We investigate how the chemokine module of CXCL12/ CXCR4 and CXCR7 regulates interneuron development. We focus on the molecular regulation of atypical CXCR7, which functions as a molecular sink for CXCL12 und thus regulates CXCL12/ CXCR4 chemotactic signaling. In addition, we address b-Arrestin-dependence of chemokine-regulated cell migration.

Further projects

Real-time analysis of phosphorylation and dephosphorylation of the μ-opioid receptor
Principle investigator: Prof. Dr. Stefan Schulz
DFG SFB_TRR166 2015 – 2019

Selected publications

Saaber F, Schütz D, Miess E, Abe P, Desikan S, Ashok Kumar, P, Balk S, Huang K, Beaulieu JM, Schulz S, Stumm R: ACKR3 Regulation of neuronal migration requires ACKR3 phosphorylation, but not β-Arrestin. Cell Rep. 26(6):1473-1488.e9, 2019
Mann A, Moulédous L, Froment C, O'Neill PR, Dasgupta P, Günther T, Brunori G, Kieffer BL, Toll L, Bruchas MR, Zaveri NT, Schulz S: Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists. Sci Signal. 12(574), 2019
Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, Williams JT, Christie MJ , Schulz S: Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects. Nat Commun. 10(1):367, 2019
Werner Y, Mass E, Ashok Kumar P, Ulas T, Händler K, Horne A, Klee K, Lupp A, Schütz D, Saaber F, Redecker C, Schultze JL, Geissmann F, Stumm R: CXCR4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke. Nat Neurosci. 23:351-362, 2020
Kliewer A, Gillis A, Hill R, Schmidl F, Baily C, Kelly E, Henderson GJ, Christie MJ, Schulz S: Morphine-induced respiratory depression is independent of ß-arrestin2 signalling. Br J Pharmacol. 177:2923-2931, 2020