Brian Gulbransen, Ph.D.
The goal of my research is to understand how inflammation in the nervous system (neuroinflammation) leads to long-term changes in neural circuitry. Within this context, we focus on the regulation of neural networks by glial cells, with particular interests in clarifying the role of glial cells in nervous system physiology and elucidating how glial changes during neuroinflammation contribute to disease. We are addressing this issue by exploring how neuron-glia interactions in the enteric nervous system (ENS) regulate intestinal physiology and pathophysiology. Our experiments are designed to allow us to understand the fundamental rules that govern cell-to-cell communication in the ENS, and to elucidate the molecular machinery that contributes to changes in enteric network output. We use a diverse array of techniques including, but not limited to, calcium imaging with genetically encoded indicators, chemogenetics, optogenetics, genomics, intestinal disease models, and in vivo and in vitro physiological assays. This work is important because it will lead to an understanding of the basic mechanisms that underlie disturbed intestinal functions in motility disorders, functional bowel disorders, and visceral pain. These are debilitating conditions that affect up to 25% of humans and account for over $30 billion/year in healthcare costs in the U.S. alone. It is also likely that the basic rules of neuron-glia interactions we uncover will broaden the understanding of how neural networks are regulated by glia in other branches of the nervous system and benefit the development of treatments for non-intestinal nervous system disorders.
Complete List of Published Work in MyBibliography.
Morales-Soto W and Gulbransen BD (2018). Enteric Glia: A New Player in Abdominal Pain. Cell Mol Gastroenterol Hepatol. Nov 24;7(2):433-445. DOI: http://dx.doi.org/10.1016/j.jcmgh.2018.11.005. PMID: 30739868.
Delvalle NM, Dharshika C, Morales-Soto W, Fried DE, Gaudette L and Gulbransen BD. (2018) Communication between enteric neurons, glia, and nociceptors underlies the effects of tachykinins on neuroinflammation. Cell Mol Gastroenterol Hepatol. May 29;6(3):321-344. PMID: 30116771.
Delvalle NM, Fried DE, Rivera-Lopez G, Gaudette L, Gulbransen BD. (2018) The cholinergic activation of enteric glia is a physiological mechanism that contributes to the regulation of gastrointestinal motility. American Journal of Physiology - Gastrointestinal and Liver Physiology. Oct 1; 315(4):G473-G483. PubMed PMID: 29927320.
Grubišić V, Gulbransen BD. (2017) Enteric glia: the most alimentary of all glia. J Physiol. Jan15;595(2):557-570. PMCID: PMC5233670.
Grubišić V, Gulbransen BD. (2017) Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability. J Physiol. 595(11):3409-3424. PMID: 28066889.
Bubenheimer RK, Brown IAM, Fried DE, McClain JL and Gulbransen BD (2016) Sirtuin 3 regulates oxidative stress in enteric neurons but its function is not required for protection from inflammatory damage. Frontiers in Cellular Neuroscience, in press.
Brown, IAM, Mcclain, JL, Watson, RE, Patel, BA, & Gulbransen, BD (2016) Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric Oxide. Cellular and Molecular Gastroenterology and Hepatology, 2(1): 77–91. http://doi.org/10.1016/j.jcmgh.2015.08.007. PMCID: PMC4707972.
Fried DE and Gulbransen BD (2015) In situ Ca2+ imaging of the enteric nervous system. Journal of Visualized Experiments, Jan 29(95): e52506. doi:10.3791/52506 PMID: 25741967 http://www.jove.com/video/52506/in-situ-ca2-imaging-of-the-enteric-nervous-system.
Gombash SE, Cowley CJ, Fitzgerald JA, Iyer CC, Fried DE, McGovern VL, Williams KC, Burghes AHM, Christofi FL, Gulbransen BD, Foust KD (2015) SMN Deficiency Disrupts Gastrointestinal and Enteric Nervous System Function in Mice. Human Molecular Genetics, Apr 9. pii: ddv127. [Epub ahead of print] PMID: 25859009
McClain JL, Fried DE and Gulbransen BD (2015) Agonist-evoked Ca2+ signaling in enteric glia drives neural programs that regulate intestinal motility in mice. Cellular and Molecular Gastroenterology and Hepatology, 1(6):631-645. http://dx.doi.org/10.1016/j.jcmgh.2015.08.004
McClain J*, Grubiši? V*, Fried D, Gomez-Suarez RA, Leinninger GM, Sévigny J, Parpura V, Gulbransen BD (2014) Ca2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice. Gastroenterology, 146: 497-507. PMCID: PMC3935238
Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, Muruve DA, McKay DM, Beck PL, Mawe GM, Thompson RJ, Sharkey KA (2012) Activation of neuronal P2X7 receptor-Pannexin-1 mediates death of enteric neurons during colitis. Nature Medicine, 18: 600-604. doi:10.1038/nm.2679.
(highlighted by Faculty of 1000 and featured on Nature Medicine’s podcast, CBC TV News Calgary, CBC radio, QR77 Newsroom, Calgary Sun, Calgary Herald, 660 News, Ottawa Citizen, Vancouver Sun, The Province, Nanaimo Daily News, Victoria Times Colonist, StarPhoenix, Regina Leader-Post, Canada.com, Edmonton Journal, Windsor Star, and the Montreal Gazette).
Smyth D, McKay CM, Gulbransen BD, Phan VC, Wang A and McKay DM (2012) Interferon-gamma signals via an ERK1/2-ARF6 pathway to promote bacterial internalization by gut epithelia. Cellular Microbiology, 14 (8):1257-70. doi: 10.1111/j.1462-5822.2012.01796.x.
Lavoie EG*, Gulbransen BD*, Martín-Satué M, Sharkey KA, Sévigny J (2011) Ectonucleotidases in the digestive system: Special focus on NTPDase3 localization. American Journal of Physiology – Gastrointestinal and Liver Physiology, 300(4):G608-20. (*, co-first authors).
Gulbransen BD, Bains JS, Sharkey KA (2010) Enteric glia are targets of the sympathetic innervation of the myenteric plexus in the guinea pig distal colon. Journal of Neuroscience, 30: 6801-6809. (cover illustration and highlighted by Faculty of 1000).
Tizzano M, Gulbransen BD*, Vandenbeuch A, Clapp TR, Herman JP, Sibhatu HM, Churchill MEA, Silver WL, Kinnamon SC, Finger TE (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci USA, 107:3210-5. (featured in the Denver Post) (* = co-first authors).
Gulbransen BD and Sharkey KA (2009) Purinergic neuron-to-glia signaling in the enteric nervous system. Gastroenterology, 136: 1349-58 (cover illustration).
Gulbransen BD, Clapp TR, Finger TE, Kinnamon SC (2008) Nasal solitary chemoreceptor cell responses to bitter and trigeminal stimulants in vitro. Journal of Neurophysiology, 99: 2929-37.
Gulbransen B, Silver W, Finger TE (2008) Solitary chemoreceptor cell survival is independent of intact trigeminal innervation. Journal of Comparative Neurology, 508: 62-71.
Gulbransen BD and Finger TE (2005) Solitary chemoreceptor cell proliferation in adult nasal epithelium. Journal of Neurocytology, 34: 117-122.
Gulbransen BD and Sharkey KA (2012) Novel functional roles for enteric glia in the gastrointestinal tract. Nature Reviews Gastoenterology & Hepatology. doi: 10.1038 [Epub ahead of print].
Gulbransen BD (2014) Enteric Glia. Colloquium Series on Neuroglia in Biology and Medicine: From Physiology to Disease. Vol. 1, No. 2, pages 1-70. A. Verkhratsky, V. Parpura (eds.). Morgan & Claypool. doi: 10.4199/C00113ED1V01Y201407NGL002. Published Aug. 11, 2014. Link on Amazon: http://amzn.com/1615046607.
Gulbransen BD (2014) Glial Cells and Interstitial Cells of Cajal. Reference Module in Biomedical Sciences. Elsevier. Michael Caplan (ed.).
Brown I and Gulbransen BD (2014) “Enteric glial cells: Implications in gut pathology”, in Pathological potential of neuroglia. Ch. 21, pages 493-518. V. Parpura, A. Verkhratsky (eds.), doi: 10.1007/978-1-4939-0974_21. Springer Science+Business Media New York.