Rodger Alan Liddle
Professor of Medicine
Our laboratory has two major research interests:
Enteroendocrine Cell Biology
Enteroendocrine cells (EECs) are sensory cells of the gut that send signals throughout the body. They have the ability to sense food and nutrients in the lumen of the intestine and secrete hormones into the blood. Our laboratory has had a longstanding interest in two types of EECs that regulate satiety and signal the brain to stop eating. Cholecystokinin (CCK) is secreted from EECs of the upper small intestine and regulates the ingestion and digestion of food through effects on the stomach, gallbladder, pancreas and brain. Peptide YY (PYY) is secreted from EECs of the small intestine and colon and regulates satiety. We recently demonstrated that CCK and PYY cells not only secrete hormones but are directly connected to nerves through unique cellular processes called ‘neuropods’. Our laboratory is devoted to understanding EECs signaling and its role in disease.
Pancreatitis is an inflammatory disease of the pancreas compounded by intrapancreaatic activation of digestive enzymes. Our laboratory is studying the influence of nerves on the development of pancreatitis. Neurogenic inflammation results from the release of bioactive substances from sensory neurons in the pancreas causing vasodilatation, edema, and inflammatory cell infiltration producing tissue necrosis. Our goal is to identify the agents that activate sensory neurons, characterize the receptors on sensory nerves that mediate these actions, and determine the effects of neural stimulation on pancreatic injury with the long-term objective of developing strategies to reduce neurogenic inflammation to treat pancreatitis.
Neural sensing of gut bacteria awarded by National Institutes of Health (Principal Investigator). 2020 to 2025
Mechanisms of Pancreatic Fibrosis awarded by National Institutes of Health (Principal Investigator). 2020 to 2025
Endocrinology and Metabolism Training Program awarded by National Institutes of Health (Mentor). 2019 to 2024
Sensing Dietary Amino Acids from Gut to Brain awarded by National Institutes of Health (Co-Mentor). 2021 to 2024
Metabolic regulation of pancreatitis awarded by National Institutes of Health (Principal Investigator). 2020 to 2024
Mechanisms of mechanically-induced acute pancreatitis awarded by National Institutes of Health (Principal Investigator). 2019 to 2023
IPA - Katherine N. Chavez Velasquez awarded by Durham Veterans Affairs Medical Center (Principal Investigator). 2020 to 2022
IPA - Rashmi Chandra awarded by Durham Veterans Affairs Medical Center (Principal Investigator). 2020 to 2022
IPA - Sandip M. Swain awarded by Durham Veterans Affairs Medical Center (Principal Investigator). 2020 to 2022
A Novel Integrative Pathway Regulating Intestinal Glucose Sensing awarded by Pew Scholars Program (Co Investigator). 2018 to 2021
Diamond, P., and R. Liddle. “Aftershock: The post-crisis social investment welfare state in Europe.” Towards a Social Investment Welfare State?: Ideas, Policies and Challenges, 2011, pp. 285–308.
Ye, Lihua, et al. “Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways.” Cell Host Microbe, Dec. 2020. Pubmed, doi:10.1016/j.chom.2020.11.011. Full Text
Swain, Sandip M., and Rodger A. Liddle. “Piezo1 acts upstream of TRPV4 to induce pathological changes in endothelial cells due to shear stress.” J Biol Chem, Dec. 2020. Pubmed, doi:10.1074/jbc.RA120.015059. Full Text
Swain, Sandip M., et al. “TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation.” J Clin Invest, vol. 130, no. 5, May 2020, pp. 2527–41. Pubmed, doi:10.1172/JCI134111. Full Text
Ye, Lihua, et al. “High fat diet induces microbiota-dependent silencing of enteroendocrine cells.” Elife, vol. 8, Dec. 2019. Pubmed, doi:10.7554/eLife.48479. Full Text
Liddle, Rodger A. “Interactions of Gut Endocrine Cells with Epithelium and Neurons.” Compr Physiol, vol. 8, no. 3, June 2018, pp. 1019–30. Pubmed, doi:10.1002/cphy.c170044. Full Text
Romac, Joelle M. J., et al. “Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis.” Nat Commun, vol. 9, no. 1, Apr. 2018, p. 1715. Pubmed, doi:10.1038/s41467-018-04194-9. Full Text
Chiang, Ryan S., et al. “1089 Hypophosphatemia in Patients With Alcoholic Hepatitis.” American Journal of Gastroenterology, vol. 114, no. 1, Ovid Technologies (Wolters Kluwer Health), 2019, pp. S615–16. Crossref, doi:10.14309/01.ajg.0000593888.05451.17. Full Text
Himmerkus, N., et al. “Water impermeability of the thick ascending limb of Henle's loop and the collecting duct depends on ILDR1 expression.” Acta Physiologica, vol. 219, WILEY, 2017, pp. 26–28.
Kaelberer, Melanie M., et al. “128 A Gut-Brain Sensory Neuroepithelial Circuit.” Gastroenterology, vol. 150, no. 4, Elsevier BV, 2016, pp. S30–31. Crossref, doi:10.1016/s0016-5085(16)30229-3. Full Text
Shahid, Rafiq A., et al. “Bile Acid-Induced Acute Pancreatitis in Mice Is Caused by Acinar Cell Leukotriene B-4 Secretion Through a Calcium-Independent Pathway.” Gastroenterology, vol. 146, no. 5, W B SAUNDERS CO-ELSEVIER INC, 2014, pp. S297–S297.
Shahid, Rafiq A., et al. “Bile Acid-Induced Acute Pancreatitis Is Mediated by Acinar Cell Leukotriene B-4 Secretion.” Gastroenterology, vol. 144, no. 5, W B SAUNDERS CO-ELSEVIER INC, 2013, pp. S320–S320.
Chandra, Rashmi, et al. “Immunoglobulin-Like Domain Containing Receptor Mediates Fat-Stimulated Cholecystokinin Secretion.” Gastroenterology, vol. 144, no. 5, W B SAUNDERS CO-ELSEVIER INC, 2013, pp. S8–S8.
Vigna, Steven R., et al. “The Role of TRPV1 in Ethanol Plus Fatty Acid-Induced Acute Pancreatitis in Mice.” Gastroenterology, vol. 142, no. 5, W B SAUNDERS CO-ELSEVIER INC, 2012, pp. S459–60.
Shahid, Rafiq A., et al. “Leukotriene B-4 Activation of TRPV1 Mediates Acute Pancreatitis Induced by Pancreatic Duct Infusion of Sodium Taurocholate in Mice.” Gastroenterology, vol. 142, no. 5, W B SAUNDERS CO-ELSEVIER INC, 2012, pp. S316–S316.
Bohorquez, Diego V., et al. “PYY-Secreting L Cells Connect to Enteric Myofibroblasts and Neurites Through Axon-Like Basal Processes.” Gastroenterology, vol. 140, no. 5, W B SAUNDERS CO-ELSEVIER INC, 2011, pp. S148–S148.
Bohorquez, Diego V., et al. “The enteroendocrine PYY cell interacts with neurites of the enteric nervous system through axon-like basal process.” Faseb Journal, vol. 25, FEDERATION AMER SOC EXP BIOL, 2011.