Explorative projects:
Hemopressins ((x)-PVNFKLLSH) or peptide endocannabinoids (pepcans) can bind to cannabinoid receptors. RVD-hemopressin (pepcan-12) was shown to act as endogenous allosteric modulator of cannabinoid receptors, with opposite effects on CB1 and CB2, respectively. Moreover, the N-terminally elongated pepcan-23 was detected in different tissues and is postulated to be the pro-peptide of RVD-hemopressin. We are generating a conditional polypoint pepcan-12 (pro-peptide pepcan-23) specific conditional knock-in mouse strain to investigate the role of these peptides in physiology.
Papers
The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Over the last 10 years, we have generated potent and specific inhibitors to block endocannabinoid membrane transport and recently identified a novel biochemical mechanism underlying endocannabinoid reuptake.
Papers
Chagas disease remains a major public health risk in Bolivia, particularly among rural indigenous communities. In an EU project we studied the cultural perception of the triatomine vectors and Chagas disease and the botanical drugs used in to treat symptoms among selected rural and urban ethnic groups from different socio-economic and geographical milieus. We focused on the indigenous communities in the Bolivian Chaco where the disease is hyperendemic. We study the T. cruzi infection cycle in vitro to elucidate new targets, employing the CRISPR/Cas technology and metabolomics. We are interested in how T. cruzi affects the endocannabinoid system in the host cell and whether the underlying biochemical interrelation may be exploited as new antichagasic therapeutic strategy.
Papers
Absence, overexpression or malfunctioning of the amino acid transporter LAT1 is associated with human diseases, in particular tumor growth. Cancer cells have reprogramed their energy metabolism to efficiently support tumor growth and metastasis formation. This includes alterations of amino acid catabolism and upregulation of amino acid transporters that lead to the activation of crucial signalling pathways, e.g. mTOR, linking growth signals to nutrient availability.
Papers
Targeted metabolomics is a quantitative approach where a specific group of metabolites are quantified with the help of internal or external standards using LC-MS/MS. We are specialized on both endogenous molecules (lipids, amino acids and neurotransmitters) as well as xenobiotics (context of pharmacokinetics and pharmacodynamics).
Papers
The botanical drug cannabis flos (inflorescence of Cannabis sativa L.) has a unique popular status as being a potent rec-reational drug and bona fide universal remedy (panacea). Generally, cannabinoids exert therapeutic effects in a broad range of pathophysiologies related to inflammation, pain, metabolic and stress-related conditions in preclinical animal models. However, the translation of such data to humans still lacks an evidence-based foundation. We are interested in the link between secondary metabolites in food and modulation of the endocannabinoid system.
The endocannabinoid system (ECS) is a major lipid signalling network that plays important pro-homeostatic (allostatic) roles not only in the nervous system but also in peripheral organs. There is increasing evidence that there is a dietary component in the modulation of the ECS. Cannabinoid receptors in hominids co-evolved with diet, and the ECS constitutes a feedback loop for food selection and energy metabolism. Dietary secondary metabolites from vegetables and spices able to enhance the activity of cannabinoid-type 2 (CB2 ) receptors may provide adaptive metabolic advantages and counteract inflammation. In contrast, chronic CB1 receptor activation in hedonic obese individuals may enhance pathophysiological processes related to hyperlipidaemia, diabetes, hepatorenal inflammation and cardiometabolic risk. Food able to modulate the CB1 /CB2 receptor activation ratio may thus play a role in the nutrition transition of Western high-calorie diets.
Selected Papers