Christopher M Norris, Ph.D.

Bio / Education: 

BA Psychology, Washington & Jefferson College, Washington, PA, 1992
MA Experimental Psychology, Wake Forest University, Winston-Salem, NC 1994
PhD Neuroscience, University of Virginia, Charlottesville, VA, 1998

Research Description: 

Our lab uses postmortem human tissue samples, transgenic rodents, and primary neural cultures to investigate the role of activated astrocytes in neurologic dysfunction and to develop novel strategies for treating neurodegenerative conditions like Alzheimer’s disease and traumatic brain injury. Astrocyte signaling pathways (especially those regulated by the Ca2+-dependent phosphatase calcineurin) are selectively targeted in model systems using adeno-associated virus, adenovirus, and/or lentivirus vectors equipped with cell-type specific promoters. Markers of aging, injury, and/or Alzheimer’s disease are assessed using a comprehensive set of approaches including behavioral characterization, brain slice and patch clamp electrophysiology, immunohistochemistry, and a variety of molecular and biochemical techniques.

Grants: 

ONGOING SUPPORT

Calcineurin and inflammatory signaling processes in aging and Alzheimer’s Disease
5R01 AG027297 (Norris, PI) 09/01/2006 to 03/31/2017 NIH/NIA

Role of Calcineurin/NFAT signaling in traumatic brain injury
KSCHIRT (Norris, PI) 01/015/2013 to 01/14/2016

Pycnogenol and traumatic brain injury
KSCHIRT (Scheff, PI; Norris Co-I) 01/015/2013 to 01/14/2016

MIR-15/107 microRNAs are important genetic regulators in Alzheimer Disease
2R56NS061933 (Nelson, PI; Norris, Co-I) 09/28/2012-06/30/2014 NIH/NIA

Sexually dimorphic miR-497 regulates alpha-synuclein and alpha-synucleinopathy
1R21 NS085830 (PI, Nelson; Norris, Co-I); 9/22/2013-9/21/2015 NIH/NINDS

Modulation of peripheral inflammation and immune cell traffic in AD by XPro1595
Research Award(PI, Tansey; Norris Subcontract PI); 10/01/2013-9/30/2014 ADDF

Work is also supported by the Hazel Embry Alzheimers Research Fund

Selected Publications: 

RECENT PUBLICATIONS
Sudduth TL, Weekman EM, Price BR, Gooch JL, Woolums A, Norris CM, Wilcock DM (2017) Time-course of glial changes in the hyperhomocysteinemia model of vascular cognitive impairment and dementia (VCID). Neuroscience 341:42-51.

Pleiss MM, Sompol P, Kraner SD, Mohmmad Abdul H, Furman JL, Guttmann RP,
Wilcock DM, Nelson PT, Norris CM (2016) Calcineurin proteolysis in astrocytes:
Implications for impaired synaptic function. Biochimica et Biophysica Acta 1862:1521-1532.

Lovell MA, Lynn BC, Fister S, Bradley-Whitman M, Murphy MP, Beckett TL, Norris CM, (2016) A novel small molecule modulator of amyloid pathology. Journal of Alzheimer’s Disease 53:273-287.

Pettigrew LC, Kryscio RJ, Norris CM (2016) The TNFα-Transgenic Rat: Hippocampal synaptic integrity, cognition, function, and post- ischemic cell loss. PLOS ONE, 11(5): e0154721. doi:10.1371/journal.pone.0154721 -- 20 page article

Furman JL, Sompol P, Kraner SD, Pleiss MM, Putman EJ, Dunkerson J, Mohmmad Abdul H, Scheff SW, Norris CM (2016) Blockade of astrocytic calcineurin/NFAT signaling helps to normalize hippocampal synaptic function and plasticity in a rat model of traumatic brain injury. The Journal of Neuroscience 36:1502-1515.

Norris CM, Sompol P, Roberts KN, Ansari M, Scheff SW (2016) Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury. Experimental Neurology 276:5-12.

Furman JL Norris CM (2014) Calcineurin and glial signaling: Neuroinflammation and beyond. Journal of Neuroinflammation 11:158.

Gant JC, Blalock EM, Chen KC, Kadish I, Porter NM, Norris CM, Thibault O, Landfield PW (2014) FK506-binding protein 1b/12.6: A key to aging-related hippocampal Ca2+ dysregulation? European Journal of Pharmacology 739:74-82.

Niedowicz DM, Reeves VL, Platt TL, Kohler K, Beckett TL, Powell DK, Lee TL, Sexton TR, Song ES, Brewer LD, Latimer CS, Kraner SD, Larson KL, Ozcan S, Norris CM, Hersh LB, Porter NM, Wilcock DM, Murphy MP (2014) Obesity and diabetes cause cognitive dysfunction in the absence of accelerated β-amyloid deposition in a novel murine model of mixed or vascular dementia. Acta Neuropathologica Communications 2:64.

Wang W-X, Danaher J, Miller CS, Berger JR, Vega NG, Wilfred BS, Neltner JH,
Norris CM, Nelson PT (2014) Expression of MiR-15/107 family microRNAs in human tissues and rat brain cells. Genomics, Proteomics & Bioinformatics 12:19-30.

Norris CM (2014) Calpain interactions with the protein phosphatase calcineurin in
neurodegeneration. Advances in Biochemistry in Health and Disease. 8:17-45.

Sama DM, Norris CM (2013) Calcium dysregulation and neuroinflammation: Discrete and integrated mechanisms for age-related synaptic dysfunction. Ageing Research Reviews, In Press.

Furman JL, Sama DM, Gant JC, Beckett TL, Murphy MP, Bachstetter AD, Van Eldik LJ, Norris CM (2012) Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer’s disease. The Journal of Neuroscience 32: 16129 –16140.

Bachstetter AD, Norris CM, Sompol P, Wilcock DM, Goulding D, Neltner JH, St Clair D, Watterson DM, Van Eldik LJ (2012) A small molecule suppressor of proinflammatory cytokine production attenuates glial activation and prevents synaptic dysfunction in an Alzheimer’s disease transgenic mouse model. The Journal of Neuroscience 32:10201–10210.

Sama DM, Mohammad-Abdul, H, Furman JL, Szymkowski DE, Scheff SW, Norris CM (2012) Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats. PLoS ONE 7(5):e38170.

Thibault O, Pancani T, Landfield PW, Norris CM (2012) Reduction in neuronal L-type Ca2+ channel current density in hippocampal “zipper” slices from mid-age memory-deficient APPxPS1 mice. Biochimica et Biophysica Acta 1822:546-549.

Gant JC, Chen K-C, Norris CM, Thibault O, Blalock EM, Porter NM, Landfield PW (2011) Rapamycin or knockdown of FKBP12.6/1b recapitulates aging-like Ca2+ dysregulation in hippocampal neurons. The Journal of Neuroscience 31:1593-1603

Mathis DM, Furman JL, Norris CM (2011) Preparation of acute hippocampal slices from rats and transgenic mice for the study of synaptic alterations during aging and amyloid pathology. Journal of Visualized Experiments 49: http://www.jove.com/details.stp?id=2330

Mohmmad Abdul H, Baig I, Levine, H III, Guttmann RP, Norris CM (2011) Proteolysis of calcineurin is increased in human hippocampus during mild cognitive impairment and is stimulated in primary cultures by oligomeric Abeta. Aging Cell 10: 103-113.

Norris CM, Blalock EM, Chen K-C, Porter, NM, Thibault O, Kraner SD, Landfield PW (2010) Hippocampal ‘zipper’ slice studies reveal a necessary role for calcineurin in the increased activity of L-type Ca2+ channels with aging. Neurobiology of Aging 31:328–338.

Abdul MH, Furman JL, Sama MA, Mathis DM, Norris CM (2010) NFATs and Alzheimer’s disease. Molecular and Cellular Pharmacology 2:7-14.

Furman JL, Sama MA, Artiushin IA, Norris CM (2010) Disparate effects of serum on basal and evoked NFAT activity in primary astrocyte cultures. Neuroscience Letters 469:365–369.

Abdul MH, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, Patel ES, Baig I, Levine, H III, Murphy MP, Kraner SD, Norris CM (2009) Cognitive decline in Alzheimer’s disease is associated with selective changes in calcineurin/NFAT signaling. The Journal of Neuroscience 29:12957–12969.

Norris CM, Scheff SW (2009) Recovery of afferent function and synaptic strength in hippocampal CA1 following traumatic brain injury. Journal of Neurotrauma 26:2269–2278.

Sama MA, Mathis DM, Furman JL, Artiushin IA, Mohmmad Abdul H, Kraner SD, Norris CM (2008) Interleukin-1-dependent signaling between glia and neurons depends critically on astrocytic calcineurin/NFATactivity. Journal of Biological Chemistry 283:21953-21964

Jeftinija DM, Hebert SL, Norris CM, Wang QB, Rich MM, Kraner SD (2007) The CaV 1.2 Ca2+ channel is expressed in the sarcolemma of type I and IIa skeletal muscle fibers. Muscle & Nerve 36: 482–490.

Norris CM, Blalock EM, Thibault O, Brewer LD, Clodfelter GV, Porter, NM, Landfield PW (2006) Electrophysiological mechanisms of delayed excitotoxicity: Positive feedback loop between NMDA receptor current and depolarization-mediated glutamate release. Journal of Neurophysiology 96:2488-2500.

Blalock EM, Chen K-C, Stromberg AJ, Norris CM, Kadish I, Kraner SD, Porter NM, Landfield PW (2005) Harnessing the power of gene microarrays for the study of brain aging and Alzheimer’s disease: Statistical reliability and functional correlation. Ageing Research Reviews 4:481-512.

Norris CM, Kadish I, Blalock EM, Chen KC, Thibault V, Porter NM, Landfield PW, Kraner SD (2005) Calcineurin triggers reactive/inflammatory processes in astrocytes and is upregulated in aging and Alzheimer’s models. The Journal of Neuroscience 25:4649-4658.