Picture of Dr. Sean Mulligan

Dr. Sean Mulligan BSc, MSc, PhD Faculty, Physiology

About Dr. Sean Mulligan

Neuroscience Research Group, College of Medicine, University of Saskatchewan
Postdoctoral Fellow (Psychiatry) Faculty of Medicine, University of British Columbia
Ph.D. (Neuroscience) Faculty of Medicine, University of Calgary
M.Sc. (Biology/Neurobiology) Simon Fraser University
B.Sc. (Biomedical Physiology/Kinesiology) Simon Fraser University

Teaching Interests

  • Neuroscience
  • Recipient of the 2013 University of Saskatchewan Provost's College Award for Outstanding Teaching
  • Recipient of the 2011 University of Saskatchewan Students’ Union Teaching Excellence Award

Research Interests

The objective of our research is to gain insight into the mechanisms of peripheral pain signaling. We are developing novel optical imaging approaches for both ex vivo and in vivo work, to directly study physiological functioning at the level of individual pain fibre free nerve endings. High-resolution functional optical imaging provides us with an opportunity to study the fundamental processes of activation, transduction, sensitization, and propagation of the nociceptive signal. This opens up a new window for examining physiological functioning in pain fibres and to advance our understanding of the peripheral processes involved in pain pathophysiology. It is our hope that our research will lead to the development of new peripheral drug targets that may offer novel therapeutic treatments for pain associated with the conditions of Migraine, Diabetes, and Multiple Sclerosis.

Laboratory Techniques

We are primarily an optical imaging laboratory that uses both two-photon laser scanning imaging as well as widefield epifluorescence microscopy. Microscopes are configured for both microfluorometric and transmitted light imaging using photomultiplier tube or high sensitivity EMCCD camera based detection. We combine optical imaging of ionic signaling selectively within individual pain fibre terminals with electrophysiological stimulation, pharmacological manipulations, and UV and two-photon photolysis of caged compounds.

Selected Publications

Manuscripts

Peripheral μ-opioid receptor mediated inhibition of calcium signaling and action potential-evoked calcium fluorescent transients in primary afferent CGRP nociceptive terminals.
Baillie LD, Schmidhammer H, Mulligan SJ.
Neuropharmacology. 2015 Feb 24;93C:267-273. doi: 10.1016/j.neuropharm.2015.02.011.

Exosomal pMHC-I complex targets T cell-based vaccine to directly stimulate CTL responses leading to antitumor immunity in transgenic FVBneuN and HLA-A2/HER2 mice and eradicating trastuzumab resistant tumor in athymic nude mice.
Wang L, Xie Y, Ahmed KA, Ahmed S, Sami A, Chibbar R, Xu Q, Kane SE, Hao S, Mulligan SJ, Xiang J.
Breast Cancer Res Treat. 2013 Jul;140(2):273-84. doi: 10.1007/s10549-013-2626-7.

Extracellular pH and neuronal depolarization serve as dynamic switches to rapidly mobilize trkA to the membrane of adult sensory neurons.
Bray GE, Ying Z, Baillie LD, Zhai R, Mulligan SJ, Verge VM.
J Neurosci. 2013 May 8;33(19):8202-15. doi: 10.1523/JNEUROSCI.4408-12.2013.

Dynamic volume changes in astrocytes are an intrinsic phenomenon mediated by bicarbonate ion flux.
Florence CM, Baillie LD, Mulligan SJ.
PLoS One. 2012;7(11):e51124. doi: 10.1371/journal.pone.0051124.

Sumatriptan inhibition of N-type calcium channel mediated signaling in dural CGRP terminal fibres.
Baillie LD, Ahn AH, Mulligan SJ.
Neuropharmacology. 2012 Sep;63(3):362-7. doi: 10.1016/j.neuropharm.2012.04.016.

Direct in vivo evidence of CD4+ T cell requirement for CTL response and memory via pMHC-I targeting and CD40L signaling.
Ahmed KA, Wang L, Munegowda MA, Mulligan SJ, Gordon JR, Griebel P, Xiang J.
J Leukoc Biol. 2012 Aug;92(2):289-300. doi: 10.1189/jlb.1211631.

A distinct role of CD4+ Th17- and Th17-stimulated CD8+ CTL in the pathogenesis of type 1 diabetes and experimental autoimmune encephalomyelitis.
Ankathatti Munegowda M, Deng Y, Chibbar R, Xu Q, Freywald A, Mulligan SJ, van Drunen Littel-van den Hurk S, Sun D, Xiong S, Xiang J.
J Clin Immunol. 2011 Oct;31(5):811-26. doi: 10.1007/s10875-011-9549-z.

Th17 and Th17-stimulated CD8+ T cells play a distinct role in Th17-induced preventive and therapeutic antitumor immunity.
Ankathatti Munegowda M, Deng Y, Mulligan SJ, Xiang J.
Cancer Immunol Immunother. 2011 Oct;60(10):1473-84. doi: 10.1007/s00262-011-1054-y.

Functional imaging within individual pain fibres ex vivo with optical microscopy.
Baillie LD, Hagen V, Gardner KM, Mulligan SJ.
J Neurosci Methods. 2011 Jun 15;198(2):274-9. doi: 10.1016/j.jneumeth.2011.04.015.

Opposing actions of endothelin-1 on glutamatergic transmission onto vasopressin and oxytocin neurons in the supraoptic nucleus.
Zampronio AR, Kuzmiski JB, Florence CM, Mulligan SJ, Pittman QJ.
J Neurosci. 2010 Dec 15;30(50):16855-63. doi: 10.1523/JNEUROSCI.5079-10.2010.

Microglia processes block the spread of damage in the brain and require functional chloride channels.
Hines DJ, Hines RM, Mulligan SJ, Macvicar BA.
Glia. 2009 Nov 15;57(15):1610-8. doi: 10.1002/glia.20874.

CD4+ Th-APC with acquired peptide/MHC class I and II complexes stimulate type 1 helper CD4+ and central memory CD8+ T cell responses.
Umeshappa CS, Huang H, Xie Y, Wei Y, Mulligan SJ, Deng Y, Xiang J.
J Immunol. 2009 Jan 1;182(1):193-206. 

Dendritic vasopressin release: reducing the flow makes blood vessels grow.
Pittman QJ, Mulligan SJ.
Endocrinology. 2008 Sep;149(9):4276-8. doi: 10.1210/en.2008-0871.

D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.
Kisilevsky AE, Mulligan SJ, Altier C, Iftinca MC, Varela D, Tai C, Chen L, Hameed S, Hamid J, Macvicar BA, Zamponi GW.
Neuron. 2008 May 22;58(4):557-70. doi: 10.1016/j.neuron.2008.03.002.

Astrocyte control of the cerebrovasculature.
Gordon GR, Mulligan SJ, MacVicar BA.
Glia. 2007 Sep;55(12):1214-21. Review.

VRACs CARVe a path for novel mechanisms of communication in the CNS.
Mulligan SJ, MacVicar BA.
Sci STKE. 2006 Oct 17;2006(357):pe42. Review.

Calcium transients in astrocyte endfeet cause cerebrovascular constrictions.
Mulligan SJ, MacVicar BA.
Nature. 2004 Sep 9;431(7005):195-9.

Mitral cell presynaptic Ca(2+) influx and synaptic transmission in frog amygdala.
Mulligan SJ, Davison I, Delaney KR.
Neuroscience. 2001;104(1):137-51.

Book Chapters

Two-Photon Laser Scanning Microscopy: Imaging Astrocyte Calcium Signalling in the Brain Slice Preparation.
Florence CM, Mulligan SJ
In Neuromethods series, edited by Walz, W. and Doucette, R., Humana Press (2010).

Astrocyte control of blood flow.
Gordon GR, Mulligan SJ, MacVicar BA.
In Astrocytes in (patho)physiology of the nervous system, edited by Parpura, V. and Haydon P.G, Springer (2009).

Glia Control of Blood Flow.
Gordon GR, MacVicar BA, Mulligan SJ
In The New Encyclopedia of Neuroscience, edited by Squire, L.R., Oxford:Academic Press (2009).

Two-Photon Fluorescence Microscopy: Basic Principles, Advantages and Risks.
Mulligan SJ, MacVicar BA
In Modern Research and Educational Topics in Microscopy, edited by A. Méndez-Vilas, J. Díaz, Formatex (2007).

Intrinsic Optical Signal Imaging in Brain slices.
MacVicar BA, Mulligan SJ
In Imaging in Neuroscience and Development: A Laboratory Manual, edited by Yuste, R. and Konnerth, A., Cold Spring Harbor Laboratory Press. (2005).

Monitoring Intracellular Ca2+ in Brain Slices with Fluorescent Indicators.
Mulligan SJ, MacVicar BA
In Voltage-Gated Calcium Channels, edited by Zamponi, G.W., Landes Bioscience (2005).