Welcome to the Gertsch Lab

Our Research

We investigate how small organic molecules interact with biological systems, unraveling the molecular mechanisms that drive complex biochemical and physiological processes. Our research bridges chemistry and biology, using these molecules as powerful tools to probe molecular pharmacology, with a special focus on the endocannabinoid system and lipid-based signaling.

We specialize in highly apolar membrane lipids and their roles in health and disease. Our transdisciplinary approach integrates LC-MS/MS analytics, chemical biology, transgenic animal models, human blood analyltics, biochemistry, and molecular biology to decode biological pathways and uncover new drug targets.

Our research is deeply translational, aimed at linking molecular insights to therapeutic innovation. We are especially passionate about neuropharmacology and the discovery of natural products as bioactive compounds, studying their convergent evolution across diverse life forms, from mammals and plants to Trypanosoma cruzi. Currently we work in three different areas:

1. Endocannabinoid System

Gertsch Lab spin-off Synendos Therapeutics with a phase I clinical lead generated in our laboratory.

2. The food medicine continuum

SNSF Sinergia Grant and Tasteomics spin-off with a new technology discovered and developed in the Gertsch lab

3. Chagas disease

High-end Analytics

High-end analytics: LC-MS/MS

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The endocannabinoid system

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Screening Technologies

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Synthesis of novel chemical probes

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Phytocannabinoids and medical Cannabis

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Biochemical profiling of small molecules

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Peptide Endocannabinoids

Peptide endocannabinoids: Discovery of pepcan-23 as propeptide of RVD-hemopressin (pepan-12)

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ABISciex 5500 QTrap Technology

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Preclinical Mouse Models

Preclinical mouse models
Pharmacokinetics & Pharmacodynamics

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Innate Immune System

The prostaglandin-endocannabinoid axis in macrophages

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Targeted metabolomics for blood analytics & biomakers

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News & Media

Current Research Projects

News & Recent Publications

Examplary Research Papers

Carboxylesterase 1-mediated endocannabinoid metabolism in skin: role in melanoma progression in BRaf^V600E/Pten^-/- mice. Morozova V, Pellegata D, Charles RP, Gertsch J. Cancer Metab. 2025, 13(1):8.

Unovering the psychoactivity of a cannabinoid from liverworts associated with a legal high. Chicca A, Schafroth M, Reynoso-Moreno I, Erni E, Petrucci V, Carreira EM, Gertsch J. Science Advances, 2018, 4, 10, eaat2166.

Chemical probes to potently and selectively inhibit endocannabinoid reuptake. Chicca A, Nicolussi S, Bartholomäus R, Blunder M, Aparisi Rey A, Petrucci V, Reynoso-Moreno IDC, Viveros-Paredes JM, Dalghi Gens M, Lutz B, Schiöth HB, Soeberdt M, Abels C, Charles RP, Altmann KH, Gertsch J. PNAS, 2017, 114(25):E5006-E5015.

Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity. Soethoudt M, ... Di Marzo V, Gertsch J, Lichtman AH, Maccarrone M,Pacher P, Glass M, van der Stelt M. Nature Com., 2017, 3;8:13958.

Targeted metabolomics shows plasticity in the evolution of signaling lipids and uncovers old and new endocannabinoids in the plant kingdom. Gachet MS, Schubert, A, Calarco S, Boccard J, Gertsch J. Scientific Reports, 2017, 7:41177.

Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla. Hofer SC, Ralvenius WT, Gachet MS, Fritschy JM, Zeilhofer HU, Gertsch J. Neuropharmacology 2015, 98:78-89.

The major central endo-cannabinoid directly acts at GABA(A) receptors. Sigel E, Baur R, Rácz I, Marazzi J, Smart TG, Zimmer A, Gertsch J. PNAS , 2011,108(44):18150-5.

Beta-caryophyllene is a dietary cannabinoid. Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, Altmann KH, Karsak M, Zimmer A. PNAS 2008, 105(26):9099-104.

Recent Collaborative Research Papers

Association of endocannabinoids with pain in endometriosis.Andrieu T, Chicca A, Pellegata D, Bersinger NA, Imboden S, Nirgianakis K, Gertsch J, Mueller MD. Pain. 2021, doi: 10.1097/j.pain.0000000000002333.

Diacylglycerol lipase alpha in astrocytes is involved in maternal care and affective behaviors.Schuele LL, Glasmacher S, Gertsch J, Roggan MD, Transfeld JL, Bindila L, Lutz B, Kolbe CC, Bilkei-Gorzo A, Zimmer A, Leidmaa E. Glia. 2021, 69(2):377-391.

Design, synthesis and biological evaluation of second-generation benzoylpiperidine derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors.Granchi C, Bononi G, Ferrisi R, Gori E, Mantini G, Glasmacher S, Poli G, Palazzolo S, Caligiuri I, Rizzolio F, Canzonieri V, Perin T, Gertsch J, Sodi A, Giovannetti E, Macchia M, Minutolo F, Tuccinardi T, Chicca A. Eur J Med Chem. 2021, 209:112857.

Morozova et al. Carboxylesterase 1-mediated endocannabinoid metabolism in skin: role in melanoma progression in BRaf^V600E/Pten^-/- mice

Cancer Metab,2025,13(1):8.

Background: Melanoma is a highly aggressive skin cancer with a poor prognosis. The endocannabinoids 2-arachidonoylgylcerol (2-AG) and anandamide have been linked to melanoma progression, though their roles remain unclear. We hypothesized that the 2-AG-arachidonate-prostaglandin axis could drive aggressive melanoma progression.

Conclusions: A role of CES1 expression in skin is demonstrated for the first time. Our study suggests that 2-AG degradation to arachidonate favors melanoma progression, either reflecting the carcinogenic role of ARA or that monoacylglycerols like 2-AG and/or other CES1 substrates may exert antitumor effects, indicating that CES1 could be a potential therapeutic target. CES1 expression and high SAG, 2-AG, and ARA levels may be a signature of specific BRAF-driven malignant melanoma subtypes which are associated with discrete metabolic adaptations.

Recent Papers

J. Med Chem, 2025, 68, 9176-9201. Exploring Simple Drug Scaffolds from the Generated Database Chemical Space Reveals a Chiral Bicyclic Azepane with Potent Neuropharmacology. Carrel A et al.

Acta Neuropathol Commun. 2024 Oct 10;12(1):160. Comparative targeted lipidomics between serum and cerebrospinal fluid of multiple sclerosis patients shows sex and age-specific differences of endocannabinoids and glucocorticoids. Meier P, Glasmacher S, Salmen A, Chan A, Gertsch J.

ACS Pharmacol Transl Sci. 2024, 7(8):2424-2438. A Highly Potent, Orally Bioavailable Pyrazole-Derived Cannabinoid CB2 Receptor- Selective Full Agonist for In Vivo Studies. Chicca A, Bátora D, Ullmer C, Caruso A, Grüner S, Fingerle J, Hartung T, Degen R, Müller M, Grether U, Pacher P, Gertsch J.

Adv Biol Regul, 2021, in press. Characterization of pepcan-23 as pro-peptide of RVD-hemopressin (pepcan-12) and stability of hemopressins in mice. Glasmacher S, Gertsch J.

Cell Discovery, 2021, 7(1), 16. Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter. Yan R, Li Y, Müller J, Zhang Y, Singer S, Xia L, Zhong X, Gertsch J, Altmann KH, Zhou Q.

ACS Pharmacol Transl Sci, 2021. in press. Selective endocannabinoid reuptake inhibitor WOBE437 reduces disease progression in a mouse model of multiple sclerosis. Reynoso Moreno I., Tietz S, Vallini E, Engelhardt B, Gertsch J, Chicca A.

Glia, 2021, 69, 377-391. Diacylgylcerol lipase alpha in astrocytes is involved in maternal care and affective behaviors. Schuele LL, Glasmacher S, Gertsch J, Roggan MD, Transfeld JL, Bindila L, Lutz B, Kolbe CC, Bilkei-Gorzo A, Zimmer A, Leidmann E.

Eur J Med Chem. 2021, 209:112857. Design, synthesis and biological evaluation of second-generation benzoylpiperidine derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors. Granchi C, Bononi G, Ferrisi R, Gori E, Mantini G, Glasmacher S, Poli G, Palazzolo S, Caligiuri I, Rizzolio F, Canzonieri V, Perin T, Gertsch J, Sodi A, Giovannetti E, Macchia M, Minutolo F, Tuccinardi T, Chicca A.

Food Res Int. 2021, 141:110123. LC-HRMS/MS-based phytochemical profiling of Piper spices: Global association of piperamides with endocannabinoid system modulation. Luca SV, Minceva M, Gertsch J, Skalicka-Woźniak K.

Chemistry, 2020, in press. Synthesis of morpholine-based analogs of (-)-zampanolide and their biological activity. Altmann, KH, Bold, CP, Schürmann, J, Lucena Agell D, Diaz JF, Gertsch J.

ChemMedChem, 2021,16(1):145-154. Synthesis and Biological Evaluation of Endocannabinoid Uptake Inhibitors Derived from WOBE437. Mäder P., Barthalomäus R., Nicolussi S., Baumann A., Weis M., Chicca A., Rau M., Simao AC., Gertsch J., Altmann KH.

Oncogene, 2020, 39(14), 2948-2960. The ACSL3-LPIAT1 signaling drives prostaglandin synthesis in non-small lung cancer. Saliakoura M, Reynoso-Moreno I, Pozzato C, Rossi Sebastiano M, Galie M, Gertsch J, Konstandinidou G.

J. Am. Chem. Soc. 2020, 142(40):16953-16964. Development of high-specifitiy fluorescent probes to enable cannabinoid type 2 receptor studies in living cells. Sarrott R.C., et al.

Parasit Vectors 2019, 12(1):291. Cultural Perception of triatomine bugs and Chagas disease in Bolivia: A cross-sectional study. Salm, A., Gertsch J.

Nat. Chem. Biol. 2019, 15(5) 428-429. Scaffold and organism hopping with chemical probes. Gertsch J.

ChemMedChem, 2019, 14(17) 1590-1596. Total Synthesis of the Endocannabinoid Uptake Inhibitor Guineensine and SAR Studies. Barthalomäus R., Nicolussi S., Baumann A., Rau M, Simao AC, Gertsch J, Altmann KH.