The Morrison Lab

Richard Morrison, PhD is a Professor of Neurological Surgery and Biological Structure. His research focuses on molecular biology of neuronal cell death, proteomics and glial tumorgenesis.

Chizuru Kinoshita at work
retinal tissue culture images
Investigators/ Researchers
Research Questions
  1. How does injury (stroke) and disease (Alzheimer’s) precipitate nerve cell damage, dysfunction and death?
  2. How is mitochondrial structure and function (energy production) regulated in neurons and glia?
  3. Are the molecular pathways that regulate mitochondrial structure and function compromised in response to brain injury and disease?
Research Highlights
  1. Demonstrating a role for the p53 tumor suppressor protein in neuronal cell death.
  2. Identifying a key role for the apoptotic protein, Bax, in p53-mediated cell death signaling.
  3. Demonstrating a requirement for histone deacetylase activity in p53-mediated cell death signaling.
  4. Providing an initial characterization of the proteins regulating mitochondrial fission and fusion in neurons and glia.
  5. Demonstrating that neurons express unique, alternatively spliced forms of the proteins that regulate mitochondrial dynamics which confer the proteins with distinct activities.
Research Methods
  • Primary Neuronal and Glial Cultures
  • Various knockout mice are used to evaluate the role of apoptotic mediators
  • Lentivirus production, purification and transduction
  • Proteomics
  • Traditional biochemical techniques
    1. Polyacrylamide gel electrophoresis
    2. Western blot
    3. PCR
    4. Protein, mRNA and DNA purification
    5. Caspase cleavage assays
  • Immunostaining and Imaging
    1. Fluorescent and bright field imaging on fixed and live cells and tissues
  • cDNA microarray
  • Bioenergetics-oxygen consumption and glycolysis
Bibliography of Selected Publications
  • Morrison R.S., Kinoshita Y., Johnson M.D., Guo W. and Garden G.A. p53-dependent cell death signaling in neurons. Neurochem Res, 28:15-27, 2003.
  • Fu L., Abu-Khalil A., Morrison R.S., Geschwind D.H. and Kornblum H. I. Expression patterns of epidermal growth factor receptor and fibroblast growth factor receptor 1 mRNA in fetal human brain. J Comp Neurol., 462:265-273, 2003.
  • Yamaguchi F., Morrison R.S., Gonatas N.K., Takahashi H., Sugisaki Y., Teramoto A. Identification of MG-160, a FGF binding medial Golgi sialoglycoprotein, in brain tumors: An index of malignancy in astrocytomas. Int J Oncol., 22:1045-1049, 2003.
  • Yu L-R., Issaq H.J., Conrads T.P., Uo T., Blonder J., Janini G.M., Morrison R.S. and Veenstra T.D. Evaluation of Liquid Chromatography-Mass Spectrometry for Routine Proteome Analyses. Journal of Liquid Chromatography & Related Technologies, 26(20):3325-3336, 2003.
  • Yu L-R., Conrads T.P., Uo T., Issaq H.J., Morrison R.S. and Veenstra T.D. Evaluation of the acid-cleavable isotope-coded affinity tag reagents: application to camptothecin-treated cortical neurons. Journal of Proteome Research, 3:469-477 2004.
  • Johnson M.D., Li-Rong Y., Conrads T.P., Kinoshita Y., Uo T., Lee S.W., Smith D., Veenstra T., and Morrison R.S. Proteome Analysis of DNA Damage-Induced Neuronal Death Using High Throughput Mass Spectrometry. J. Biol. Chem., 279:26685-26697, 2004.
  • Garden G.A., Guo W., Tun C., Jayadev S., Balcaitis S., Moeller T., and Morrison R.S.. HIV Associated Neurodegeneration Requires p53 in Neurons and Microglia. FASEB J., 18(10):1141-1143, 2004. For Full Text: http://www.fasebj.org/cgi/doi/10.1096/fj.04-1676fje
  • Yu LR, Conrads T.P., Uo T., Kinoshita Y., Morrison R.S., Lucas D.A., Chan K., Blonder J., Issaq H.J., and Veenstra T.D. Global Analysis of the Cortical Neuron Proteome. Mol. and Cell. Proteomics, 3:896-907, 2004.
  • Garden G.A. and Morrison R.S. The Multiple Roles of p53 in the Pathogenesis of HIV Associated Dementia. BBRC, 331:799-809, 2005.
  • Uo. T., Kinoshita Y., and Morrison R.S. Neurons exclusively express an alternatively spliced BH3 domain only Bak isoform, N-Bak, that promotes neuronal apoptosis. J. Biol. Chem., 280:9065-9073, 2005.
  • Veenstra T.D., Conrads T.P., Hood B.L., Avellino A.M., Ellenbogen R.G., and Morrison R.S. Biomarkers: Mining the Biofluid Proteome. Molecular and Cellular Proteomics. 4:409-418, 2005.
  • Johnson M.D., Yu L-R, Conrads T.P., Kinoshita Y., Uo T., McBee J.K., Veenstra T.D., and Morrison R.S. The Proteomics of Neurodegeneration. American Journal of PharmacoGenomics., 5:259-70, 2005.
  • Elias MC, Tozer KR, Silber JR, Mikheeva S, Deng M, Morrison RS, Manning TC, Silbergeld DL, Glackin CA, Reh TA, Rostomilly RC: TWIST is expressed in human gliomas and promotes invasion. Neoplasia, 7:824-37, 2005.
  • La Spada A.R. and Morrison R.S. The Power of the Dark Side: Huntington’s Disease Protein and p53 Form a Deadly Alliance. Neuron, 47: 1-3, 2005.
  • Sikorski E.M., Uo T., Morrison R.S., and Agarwal A. Pescadillo interacts with the cadmium response element of the Human heme oxygenase-1 promoter in renal epithelial cells. J. Biol. Chem., 281:24423-30, 2006.
  • Kinoshita Y. Uo T., Jayadev S., Garden G.A., Conrads T.P., Veenstra T.D. and Morrison, R.S. Potential Applications and Limitations of Proteomics in the Study of Neurological Disease. Archives of Neurology, 63:1692-1696, 2006.
  • Tun C., Guo W., Nguyen H., Yun B., Libby R.T., Morrison R.S., Garden G.A. Activation of the extrinsic caspase pathway in cultured cortical neurons requires p53-mediated down-regulation of the X-linked inhibitor of apoptosis protein to induce apoptosis. J. Neurochem., 102:1206-1219, 2007.
  • McBee J.K., Yu L-R, Kinoshita Y, Uo T., Beyer R.P., Veenstra T.D., and Morrison R.S. Proteomic Analysis of Protein Expression Changes in a Model of Gliomagenesis. Proteomics Clin. Appl., 1:1485–1498, 2007.
  • Uo T., Kinoshita Y. and Morrison R.S. Apoptotic actions of p53 require transcriptional activation of PUMA and do not involve a direct mitochondrial/cytoplasmic site of action in postnatal cortical neurons. J. Neurosci, 27:12198-12210, 2007.
  • Jayadev S., Yun B., Nguyen H., Yokoo H., Morrison R.S. and Gwenn A. Garden. The Glial Response to CNS HIV Infection Includes p53 Activation and Increased Expression of p53 Target Genes. J. Neuroimmune Pharmacology, 2:359-30, 2007.
  • Morrison, R.S. and Veenstra, T.D. Biomarker discovery: Has it been worth it so far? Proteomics – Clin. Appl., 2:1375-1378, 2008.
  • Young JE, Taylor, JP, Garden GA, Martinez R, Tanaka F, C. Sandoval M, Smith AC, Sopher BL, Lin A, Fischbeck KH, Ellerby LM, Morrison RS, and La Spada AR. Polyglutamine-expanded androgen receptor truncation fragments activate a Bax-dependent apoptotic cascade mediated by JNK, c-Jun, and DP5/Hrk. J. Neurosci, 29:1987-1997, 2009.
  • Uo T., Veenstra T.D., Morrison R.S. Histone Deacetylase Inhibitors Prevent p53-dependent and Independent Bax-Mediated Neuronal Apoptosis Through Two Distinct Mechanisms. J. Neurosci, 29:2824-2832, 2009.
  • Uo, T., Dworzak J., Kinoshita, C., Kinoshita, Y., Inman, D.M., Horner, P.J. and Morrison, R.S. Drp1 levels constitutively regulate mitochondrial dynamics and viability in cortical neurons. (Cover illustration). Exp. Neurology, 218:274-285, 2009.
  • Mihkeev A., Stoll E, Mikheeva S, Maxwell JP, Ray S, Morrison R S., Uo T. , Horner P, Rostomily R. A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy. Aging Cell, 8: 499-501, 2009.
  • Baltan S., Inman D.M., Danilov C., Morrison R.S., Calkins D.J. and Horner P.J. Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration. (Cover illustration). J. Neurosci, 30: 5644-5652, 2010.
  • Waybright T., Avellino A.M., Ellenbogen R.G., Hollinger B.J., Yi M., Stephens R.S., Morrison R.S., Veenstra, T.D. Proteomic Characterization of Human Ventricular Cerebrospinal Fluid From Patients with Hydrocephalus. J. Proteomics, 73:1156-1162, 2010.
  • Baltan S., Danilov CA., Bachleda A., Murphy S.P. and Morrison R.S. Class I Histone Deacetylase Inhibitors Preserve Glial Cell Function and Viability to Protect White Matter From Ischemic Injury. Submitted, 2010.
  • Jayadev S., Case A., Eastman A.J., Nguyen H. Pollak J. Wiley J.C., Moller T., Morrison R.S. and Garden G.A. Presenilin 2 is the Predominant gamma-secretase in Microglia and Modulates Cytokine Release. PLoS ONE, 5:e15743, 2010.
  • Jayadev S, Nesser NK, Hopkins S, Myers SJ, Case A, Lee RJ, Seaburg LA, Uo T, Murphy SP, Morrison RS, Garden GA. Transcription factor p53 influences microglial activation phenotype. Glia. 2011. PMID:21598312 .
  • Baltan S., Danilov CA., Bachleda A., Murphy S.P. and Morrison R.S. Class I Histone Deacetylase Inhibitors Preserve Glial Cell Function and Viability to Protect White Matter From Ischemic Injury. J. Neurosci, 31(11): 3990-3999, 2011
  • Declines in Drp1 and Parkin Expression Underlie DNA Damage-Induced Changes in Mitochondrial Length and Neuronal Death. J. Neurosci, 33(4): 1357-1365, 2013
Contact Information

For more information about the Morrison Lab, call (206) 543-9763.