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
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 vascular contributions to cognitive impairment and dementia. 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, vascular injury, and/or Alzheimer’s disease are assessed using a comprehensive set of approaches including multiphoton microscopy, brain slice and patch clamp electrophysiology, immunohistochemistry, behavioral characterization, and a variety of molecular and biochemical techniques. We are a highly collaborative group with shared grants and manuscripts with colleagues across the Center on Aging, Department of Pharmacology, and College of Medicine.
Calcineurin and inflammatory signaling processes in aging and Alzheimer’s Disease
RF1 AG027297 (Norris, PI) 09/01/2006 to 04/30/2023 NIH/NIA
Preclinical evaluation of tacrolimus in a canine model of Alzheimer's disease
R01 AG056998 (Head/Norris, Multi-PI) 9/15/2017 to 5/31/2022 NIH/NIA
Q134R in a canine model of aging and Alzheimer disease
Aperus Pharma Inc. (Norris/Head, Multi-PI) 5/01/2018 to 4/30/2020
Elucidating the Role of Placental Growth Factor in Diffuse White Matter Disease
1R01NS116990-01 (Wilcock PI/Norris, Co-I) 04/01/2020 to 03/31/2025
Neurovascular astrocyte dysfunction in VCID
R01NS097722 (Wilcock, PI/Norris, Co-I) 9/01/2017 to 9/30/2022 NIH/NINDS
Pre-clinical efficacy of a selective p38MAPK inhibitor in a model of comorbid Alzheimer/vascular pathology
RF1AG064859-01 (Van Eldik PI / Norris, Co-I) 8/15/2019 to 9/30/2024
RIT1-mediated Protection following Traumatic Brain Injury
1R01NS102196 (Andres, PI/Norris, Co-I) 10/01/2017 – 09/30/2022 NIH/NINDS
Cell-specific actions of IL-1 / IL-1R1 signaling following traumatic brain injury
R01NS099025-01 (Bachstetter, PI/Norris Co-I) 12/15/2018 – 11/30/2023 NIH/NINDS
Inflammatory contributions of astrocytic RelA in comorbid VCID/AD
RF1NS118558 (Morganti, PI / Norris, Co-I) 09/15/2020-03/31/2025
Work is also supported by the Hazel Embry Alzheimers Research Fund
Frazier HL, Anderson KL, Ghoweri AO, Lin RL, Hawkinson TR, Popa GJ, Sompol P, Mendenhall MD, Norris CM, Thibault O (2020) Molecular elevation of insulin receptor signaling improves memory recall in aged Fischer 344 rats. Aging Cell, 19(10):e13220. doi: 10.1111/acel.13220. Epub 2020 Aug 27
Fu X, Sompol P, Brandon JA, Norris CM, Wilkop T, Johnson LA, Richards CI (2020) In vivo single-molecule detection of nanoparticles for multiphoton fluorescence correlation spectroscopy to quantify cerebral blood flow. Nano Letters, 20:6135-6141.
Dufort-Gervais J, Provost C, Charbonneau L, Norris CM, Calon F, Mongrain V, Brouillette J (2020) Neuroligin-1 is altered by amyloid-beta oligomers and modulates their toxicity. Scientific Reports, 10:6956. doi: 10.1038/s41598-020-63255-6.
Gollihue JL, Norris CM (2020) Astrocyte mitochondria: Central players and potential therapeutic targets for neurodegenerative diseases and injury. Ageing Research Reviews, 59:101039. doi: 10.1016/j.arr.2020.101039.
Quadri Z, Johnson N, Zamudioa F, Miller A, Peters M, Smeltzer S, Hunt JB, Housley SB, Brown B, Kraner SD, Norris CM, Nash K, Weeber E, Lee DC, Selenica M-L (2020) Overexpression of human wtTDP-43 causes impairment in hippocampal plasticity and behavioral deficits in CAMKII-tTa transgenic mouse model. Molecular and Cellular Neuroscience, 102:103418. doi: 10.1016/j.mcn.2019.103418.
Thalman SW, Powell DK, Ubele M, Norris CM, Head E, Lin AL (2019) Brain-blood partition coefficient and cerebral blood flow in canines using Calibrated Short TR Recovery (CaSTRR) correction method. Frontiers in Neuroscience, 13:1189. doi: 10.3389/fnins.2019.01189.
Braun D, Abner EL, Bakshi V, Goulding D, Grau EM, Lin AL, Norris CM, Sudduth TL, Webster SJ, Wilcock DM, Van Eldik LJ (2019) Blood flow deficits and cerebrovascular changes in a hyperhomocysteinemia model of vascular cognitive impairment and dementia. ASN Neuro, 11:1759091419865788 doi: 10.1177/1759091419865788.
Frazier HN, Anderson KL, Maimaiti S, Ghoweri AO, Kraner SD, Popa GJ, Hampton KK, Mendenhall MD, Norris CM, Craven RJ, Thibault O (2019) Expression of a constitutively active human insulin receptor in hippocampal neurons elevates signaling but does not alter VGCC currents. Neurochemical Research, 44:269-280.
Norris CM (2018) Calcineurin: Directing the damage in Alzheimer’s disease? Journal of Neurochemistry 147:8-11.
Kraner SD, Norris CM (2018) Astrocyte activation and the calcineurin/NFAT pathway in cerebrovascular disease. Frontiers in Aging Neuroscience, 10:287. doi: 10.3389/fnagi.2018.00287
Sompol P, Norris CM (2018). Ca2+, astrocyte activation, and calcineurin/NFAT signaling in age-related neurodegenerative diseases. Frontiers in Aging Neuroscience, 10:199. doi: 10.3389/fnagi.2018.00199.
Castonguay D, Dufort-Gervais J, Ménard C, Chatterjee M, Quirion R, Bontempi B, Schneider JS, Arnsten AFT, Nairn AC, Norris CM, Ferland G, Bézard E, Gaudreau P, Lombroso PL, Brouillette J (2018) The tyrosine phosphatase STEP is involved in age-related memory decline. Current Biology, 28:1079-1089.
Price PR, Sompol P, Norris CM, Wilcock DM (2018) An emerging role of astrocytes in vascular contributions to cognitive impairment and dementia (VCID). Journal of Neurochemistry, 144:644-650.
Sompol P, Furman JL, Pleiss MM, Kraner SD, Artiushin IA, Batten SR, Quintero JE, Simmerman LA, Beckett TL, Lovell MA, Murphy MP, Gerhardt GA Norris CM (2017) Calcineurin/NFAT signaling in activated astrocytes drives network hyperexcitability in Aβ-bearing mice. The Journal of Neuroscience, 37:6132-6148.
Manocha GD, Ghatak A, Puig KL, Kraner SD, Norris CM, Combs KL (2017) NFATc2 Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer’s Disease. Journal of Alzheimer’s Disease, 58:775-787.
MacPherson KP, Sompol P, Kannarkat G, Chang J, Sniffen L, Wildner ME, Norris CM, Tansey MG (2017) Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiology of Disease, 102:81-95.
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.