Schlichter
Lyanne SchlichterPhD
Professor
Neuroscience Platform

Contact Info

T. (416) 603-5800 Ext. 2052
F. (416) 603-5970 x416

Location

Krembil Discovery Tower 7KD417, Toronto Western Hospital, 60 Leonard Street
Toronto
ON, M5T 2S8

Research Interests

Cellular Electrophysiology / Patch-Clamp Electrophysiology / Fluorescence Imaging / Cellular Neuroimmunology / Cellular Neurobiology

Accepting

None

Appointments

Physiology

Degrees: Ph.D.

Affiliations: Toronto Western Research Institute

Courses Taught: PSL1048 (Course Coordinator); PSL 1053

Research/Teaching

Research Synopsis:

Research Interests:
Cell physiology: Microglial activation (incl. signaling pathways), gene expression changes, cell functions (e.g., migration/invasion, Ca2+ signaling, phagocytosis, proliferation, respiratory burst, cytokine production, neurotoxicity, neuroprotection)
Ion channels: Expression, properties, regulation, roles in cell physiology (functions, as above)
Neuroimmunology: in vivo rodent models of ischemic stroke, intracerebral hemorrhage; evolution of injury; indicators of damage; effects of aging; inflammation and white-matter damage

Detailed Description: My laboratory focus on neuroinflammation comprises 3 main research topics (briefly described below). Experimental approaches range from in vivo models → cell cultures → molecules. Current projects combine two or more principle techniques, and will appeal to students and postdoctoral fellows with backgrounds in neuroscience, stroke, cell physiology, electrophysiology, molecular biology, and biochemistry. We have published many seminal papers on microglia, ion channels, and in vivo studies of inflammation and CNS damage. The lab has been continually well-supported by grants from national granting agencies (CIHR, Heart & Stroke Foundation, Canadian Stroke Network, NSERC), as well as scholarships and fellowships.

Acute inflammation and damage in the CNS

  • in vivo rodent models of ischemic and hemorrhagic stroke
  • Defining the spatial and temporal evolution of inflammation and damage
  • Role of inflammation in white-matter injury
  • Assessing the effects of aging on inflammation and damage
  • Molecular/bioinformatic analysis of stroke and hemorrhage in rodent models
  • Modifying the outcome by controlling CNS inflammation

Microglia: Activation and functions of the CNS innate immune cell

  • Defining modes of microglial activation at molecular and functional levels
  • Identifying products and targets for controlling harmful microglial functions
  • Analyzing activation-dependent changes in microglial functions; e.g., proliferation, phagocytosis, migration/invasion, production of pro- and anti-inflammatory molecules

Expression and regulation and roles of ion channels in microglia

  • Molecular analysis of ion-channel expression as a function of microglial activation states. Channels include: K+, Cl-, TRP, Ca2+, Ca2+-activated K+ channels
  • Electrophysiological analysis of their biophysical and pharmacological properties
  • Regulation of channel expression, subcellular targeting, and functions, by signaling pathways relevant to microglial activation
  • Identifying roles of ion channels in microglial functions

METHODS USED

Cell and Tissue Cultures: Brain slices, microglia, astrocytes

Procedures: EEG, HPLC, Gene expression analysis, Immunocytochemistry, In vitro electrophysiology, Patch Clamp, Proteomics, qRT-PCR, RT-PCR, Signal transduction characterization, siRNA, Stereotaxic brain surgery, Western blot, NanoString, Calcium imaging, many cell functional assays (e.g., migration, phagocytosis)

EQUIPMENT USED

Amplifier, analytical balances, benchtop centrifuge, blotting apparatus, calcium imaging system, confocal microscope, culture hood, culture incubators, cryostat, deconvolution fluorescence microscope, digital microscope, dissecting microscope, electrophysiology rig, fluorescence microscope, gel apparatus, low- and high-speed centrifuge, micropipette puller, microwave oven, plate reader, real-time/thermocycler, stirrer/hot plate, vibrato me, water baths.

PRESENT TRAINEES

Jayalakshmi Caliaperumal
Michael Joseph
Doris  Lam
Starlee Lively
Tamjeed Siddiqui
Raymond Wong

PRESENT COLLABORATIONS

Within the Department of Physiology
Elise Stanley
Taufik Valiante

Outside the Department of Physiology:
Jasna Kriz, Psychiatry and Neuroscience/Laval University/Quebec /Canada

Publications and Awards

Recent Publications

  1. KCa3.1/IK1 Channel Regulation by cGMP-Dependent Protein Kinase (PKG) via Reactive Oxygen Species and CaMKII in Microglia: An Immune Modulating Feedback System?
    Ferreira R, Wong R, Schlichter LC. Front Immunol. 2015 Apr 8;6:153. doi: 10.3389/fimmu.2015.00153. eCollection 2015. PMID: 25904916
  2. PKA reduces the rat and human KCa3.1 current, CaM binding, and Ca2+ signaling, which requires Ser332/334 in the CaM-binding C terminus.  Wong R, Schlichter LC. J Neurosci. 2014 Oct 1;34(40):13371-83. doi: 10.1523/JNEUROSCI.1008-14.2014. PMID:25274816
  3. Expression and contributions of TRPM7 and KCa2.3/SK3 channels to the increased migration and invasion of microglia in anti-inflammatory activation states.  Siddiqui T, Lively S, Ferreira R, Wong R, Schlichter LC.  PLoS One. 2014 Aug 22;9(8):e106087. doi: 10.1371/journal.pone.0106087. eCollection 2014.  PMID:25148577
  4. IL-4 type 1 receptor signaling up-regulates KCNN4 expression, and increases the KCa3.1 current and its contribution to migration of alternative-activated microglia.  Ferreira R, Lively S, Schlichter LC.  Front Cell Neurosci. 2014 Jul 1;8:183. doi: 10.3389/fncel.2014.00183. eCollection 2014.  PMID:25071444
  5. Regulation of hERG and hEAG channels by Src and by SHP-1 tyrosine phosphatase via an ITIM region in the cyclic nucleotide binding domain.  Schlichter LC, Jiang J, Wang J, Newell EW, Tsui FW, Lam D.  PLoS One. 2014 Feb 28;9(2):e90024. doi: 10.1371/journal.pone.0090024. eCollection 2014. PMID: 24587194 [PubMed - in process]
  6. The microglial activation state regulates migration and roles of matrix-dissolving enzymes for invasion.  Lively S, Schlichter LC.  J Neuroinflammation. 2013 Jun 21;10:75. doi: 10.1186/1742-2094-10-75. PMID: 23786632 http://www.jneuroinflammation.com/content/10/1/75
  7. Selective activation of KCa3.1 and CRAC channels by P2Y2 receptors promotes Ca2+ signaling, store refilling and migration of rat microglial cells.  Ferreira R, Schlichter LC.  PLOS One. Vol. 8(4) e62345 (12 pages) PMID: 23620825 http://dx.plos.org/10.1371/journal.pone.0062345.
  8. Microglial SK3 and SK4 currents and activation state are modulated by the neuroprotective drug, riluzole.  Liu BS, Ferreira R, Lively S, Schlichter LC.  J Neuroimmune Pharmacol. 2013 Mar;8(1):227-37. doi: 10.1007/s11481-012-9365-0. PMID: 22527636
  9. Regulation of podosome formation, microglial migration and invasion by Ca(2+)-signaling molecules expressed in podosomes.  Siddiqui TA, Lively S, Vincent C, Schlichter LC.
    J Neuroinflammation. 2012 Nov 17;9:250. doi: 10.1186/1742-2094-9-250.  PMID: 23158496
  10. Age-Related Comparisons of Evolution of the Inflammatory Response After Intracerebral Hemorrhage in Rats.  Lively S, Schlichter LC.  Transl Stroke Res. 2012 Jul; 3(Suppl 1):132-146. Epub 2012 Mar 16.  PMID: 22707991
  11. SC1/hevin identifies early white matter injury after ischemia and intracerebral hemorrhage in young and aged rats.  Lively S, Schlichter LC.  J Neuropathol Exp Neurol. 2012 Jun; 71(6):480-93. doi: 10.1097/NEN.0b013e318256901c.  PMID: 22588386
  12. SC1/hevin and reactive gliosis after transient ischemic stroke in young and aged rats.
    Lively S, Moxon-Emre I, Schlichter LC. J Neuropathol Exp Neurol. 2011 Oct; 70(10):913-29. doi: 10.1097/NEN.0b013e318231151e.  PMID: 21937915
  13. Neutrophil depletion reduces blood-brain barrier breakdown, axon injury, and inflammation after intracerebral hemorrhage.  Moxon-Emre I, Schlichter LC.  J Neuropathol Exp Neurol. 2011 Mar; 70(3):218-35. doi: 10.1097/NEN.0b013e31820d94a5.  PMID: 21293296
  14. Inhibition of the Ca²⁺-dependent K⁺ channel, KCNN4/KCa3.1, improves tissue protection and locomotor recovery after spinal cord injury.  Bouhy D, Ghasemlou N, Lively S, Redensek A, Rathore KI, Schlichter LC, David S.  J Neurosci. 2011 Nov 9; 31(45):16298-308. doi: 10.1523/JNEUROSCI.0047-11.2011.  PMID: 22072681
  15. The Ca2+ activated SK3 channel is expressed in microglia in the rat striatum and contributes to microglia-mediated neurotoxicity in vitro.  Schlichter LC, Kaushal V, Moxon-Emre I, Sivagnanam V, Vincent C.  J Neuroinflammation. 2010 Jan 14;7:4. doi: 10.1186/1742-2094-7-4. PMID: 20074365
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