Neurogastroenterology and Chemosensing Laboratory
Key investigator
Funding
Current research projects
My research expertise is on neuronal circuits controlling gastrointestinal functions and chemosensing mechanisms underlying feeding disorders, obesity and metabolic dysfunction. Currently, there are two main lines of research in my laboratory:
- Functional characterization of neuronal-non neuronal cell connectivity of enteric neurons and signaling of µ opioid receptors in gut neurons
- Chemosensing in the gastrointestinal tract with emphasis on gut bitter taste receptors expression and regulation in condition of obesity and metabolic disease
Future research directions
- Unraveling enteric neuronal circuits that regulate colonic functions in health and disease states and the mechanisms underlying intracellular adaptations induced by chronic use of opioids
- Test the hypothesis that gut bitter taste receptors serve as sentinels detecting changes in luminal gut microbiota and mediate host functional responses by inducing release of gut peptides
Key publications
- Galligan JJ, Sternini C. Insights into the role of opioid receptors in the GI tract: Experimental evidence and therapeutic relevance. Handb Exp Pharmacol. 2017;239:363-378
- Giancola F, Torresan F, Repossi R, Bianco F, Latorre R, Ioannou A, Guarino M, Volta U, Clavenzani P, Mazzoni M, Chiocchetti R, Bazzoli F, Travagli RA, Sternini C, De Giorgio R. Downregulation of neuronal vasoactive intestinal polypeptode in Parkinson’s disease and chronic constipation. Neurogastroenterol Motil 2017; 29(5)
- Latorre R, Huyhn J, Mazzoni M, Gupta A, Bonora E, Clavenzani P, Chang L, Mayer EA, De Giorgio R, Sternini C. Expression of the bitter taste receptor, T2R38, in enteroendocrine cells of the colonic mucosa of overweight/obese vs. lean subjects. PLoS One. 2016 Feb 11;11(2):e0147468
- Anselmi L, Huynh J, Duraffourd C, Jaramillo I, Vegezzi G, Saccani F, E, Boschetti, N.C. Brecha, De Giorgio R, Sternini C. Activation of µ opioid receptor modulates inflammation in acute experimental colitis. Neurogastroenterol and Motil 2015 Feb 17. doi: 10.1111/nmo.12521. PMCID: PMC4405133
- Duraffourd C, Kumala E, Anselmi L, Brecha N, Sternini C. (2014) Opioid-Induced Mitogen-Activated Protein Kinase Signaling in Rat Enteric Neurons Following Chronic Morphine. PLOS ONE 9(9):e110230.doi: 10.1371/journal.pone.0110230. PMCID: PMC4193881
- Vegezzi G, Anselmi L, Huynh J, Barocelli E, Rozengurt E, Raybould H, Sternini C (2014). Diet-induced regulation of bitter taste receptor subtypes in the mouse gastrointestinal tract. PLOS ONE, 9(9):e107732.doi:10.1371/journal.pone.0107732. PMCID: PMC4169553
- Saccani F, Anselmi L, Jaramillo I, Bertoni S, Barocelli E, Sternini C. (2012) Protective role of µ opioid receptor activation in intestinal inflammation induced by mesenteric ischemia/reperfusion in mice. J Neurosci Res 90:2146-2153 [Epub 2012 Jul 17]. PMCID: PMC3439549
- Patierno S, Anselmi L, Jaramillo I, Scott D, Garcia R, Sternini C (2011) Morphine induces µ opioid receptor endocytosis in guinea pig enteric neurons following prolonged receptor activation. Gastroenterology 140:618-626 [Epub 2010 Nov 9]. PMCID: PMC3033567
- Sternini C, Anselmi L, Rozengurt E (2008) Enteroendocrine cells: a “site” of taste in gastrointestinal chemosensing. Current Opinion in Endocrinology and Diabetes; 15:73-78. PMCID: PMC2943060
- Sternini C (2007) Taste Receptors in the Gastrointestinal Tract IV. Functional Implications of Bitter Taste Receptors in Gastrointestinal Chemosensing. Am J Physiol Gastrointest Liver Physiol, 292:G457-G461
- Cattaruzza F, Cenac N, Barocelli E, Impicciatore M, Vergnolle N, E. Hyun, Sternini C (2006) Protective effect of proteinase-activated receptor 2 (PAR-2) activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents. Am J Pathol, 169:177-88. PMCID: PMC1698753
- Sternini C, Brecha NC, Minnis J, D’Agostino G, Balestra B, Fiori E, Tonini M. (2000) Role of agonist-dependent receptor internalization in the regulation of µ opioid receptors. Neuroscience 98:233-241.
- Sternini C, Spann M, Anton B, Keith DE, Jr., Bunnett NW, Von Zastrow M, Evans C, Brecha NC (1996) Agonist selective endocytosis of mu opioid receptor by neurons in vivo. Proceedings of the National Academy of Science USA 93:9241-9246. PMCID: PMC38626
About Dr. Sternini
Dr. Sternini's research program is focused on two major areas: 1) the neuronal circuits that form the enteric nervous system or “brain in the gut,” which regulate intestinal functions, and 2) chemosensing in the gastrointestinal tract in conditions of gut microbial imbalance and obesity. Studies on the enteric nervous system are focused on the identification of enteric neuronal circuits and their targets in health and disease states and on the mechanisms that govern receptor-mediated responses with an emphasis on the µ opioid receptors, the primary targets of opioids clinically used for pain control. Chronic use of opioids induces opioid bowel dysfunction, a debilitating condition characterized by severe constipation and abdominal pain, the treatment of which remains a major challenge. The discovery that opioids differ in their efficiency to induce receptor internalization, a key regulatory process of receptor function, in enteric neurons and that receptor trafficking and signaling pathways differ in distinct neuronal cell populations, sheds light on the mechanisms of action of opioids on enteric neurons compared to the brain, which is essential for the development of effective analgesics devoid of gastrointestinal side effects. Additional studies are focused on changes in the expression of transmitters and receptors in different pathological conditions such as intestinal ischemia, enteric neuropathies, and chronic constipation. Studies on gut chemosensing are focused on the expression and regulation of taste receptors in the gastrointestinal tract in diet-induced obesity based on the finding that bitter taste receptors, the first point of contact with foodstuff in the oral cavity that can impact on food consumption, are expressed in enteroendocrine cells in the intestine, and are upregulated in a microbiota-and diet-dependent manner. These studies are testing the innovative hypothesis that bitter taste receptors detect luminal content including bacteria and bacteria products to induce functional responses through the release of signaling molecules by enteroendocrine cells, which modulate intestinal homeostasis, caloric intake, and metabolism. Taste receptors in the gut might represent a functional link between microbiota and host leading to modulation of gut function, appetite and satiety through the brain-gut-microbiome axis and might be a potential target for obesity prevention and treatment.
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