| We study the mechanisms of cell death
following brain ischemia and reperfusion, focusing on
the causes and consequences of reperfusion-induced inhibition of protein
synthesis, or translation arrest. This translation arrest appears to
be part of the post-ischemic neuronal stress response. We have
evaluated classical ribosome biochemistry, intracellular stress
responses and most recently began investigating mRNA regulatory
mechanisms, including stress granules and HuR granules. Dr. DeGracia is currently funded by the National
Institute of Neurological Disorders and Stroke at the NIH.
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- Jamison JT, Kayali F, Rudolph J, Marshall M, Kimball
SR, DeGracia DJ. Persistent redistribution of poly-adenylated mRNAs
correlates with translation arrest and cell death following global brain
ischemia and reperfusion. Neuroscience. 2008 Apr 1. [Epub ahead of print].
- Roberts GG, Di Loreto MJ, Marshall M, Wang J,
DeGracia DJ. Hippocampal
cellular stress responses after global brain ischemia and reperfusion.
Antioxid Redox Signal. 2007 Dec;9(12):2265-75.
- DeGracia DJ, Rudolph J, Roberts GG, Rafols JA, Wang J.
Convergence of stress granules and
protein aggregates in hippocampal cornu ammonis 1 at later
reperfusion following global brain ischemia.
Neuroscience. 2007 May
11;146(2):562-72.
- DeGracia DJ & Hu BR.
Irreversible translation arrest in the reperfused brain.
J Cereb
Blood Flow Metab. 2007 May;27(5):875-93.
- DeGracia DJ, Rafols JA, Morley SJ, Kayali F.
Immunohistochemical Mapping of Total and Phosphorylated eIF4G In Rat
Hippocampus Following Global Brain Ischemia and Reperfusion. Neuroscience. 2006;139(4):1235-48.
- Kayali F, Montie HL, Rafols JA, DeGracia DJ. Prolonged
Translation Arrest in Reperfused Hippocampal CA1 Is Mediated By
Stress Granules. Neuroscience. 2005;134(4):1223-45.
- Montie HL, Haezebrouck AJ, Gutwald JC, DeGracia DJ.
PERK
Is Differentially Activated In Peripheral Organs Following Cardiac
Arrest and Resuscitation. Resuscitation. 2005
Sep;66(3):379-89.
- Montie HL, Kayali F, Haezebrouck AJ, Rossi NF, DeGracia
DJ. Renal
Ischemia and Reperfusion Activates the eIF2 alpha kinase PERK.
Biochim Biophys Acta. 2005 Sep 25;1741(3):314-24.
- DeGracia DJ, Montie HL.
Cerebral
ischemia and the unfolded protein response. J Neurochem. 2004
Oct;91(1):1-8.
- DeGracia DJ.
Acute
and persistent protein synthesis inhibition following cerebral
reperfusion. J Neurosci Res. 2004 Sep 15;77(6):771-6.
- Kumar R, Krause GS, Yoshida H, Mori K, DeGracia
DJ.
Dysfunction
of the Unfolded Protein Response During Global Brain Ischemia and
Reperfusion. J Cereb Blood Flow Metab.
2003;23:462-471.
- DeGracia DJ, Kumar R, Owen C, Krause GS, White BC.
Molecular
Pathways
of Protein Synthesis Inhibition During Brain Reperfusion:
Implications For Neuronal Survival or Death. J Cereb Blood Flow
Metab. 2002 Feb;22(2):127-141.
- Kumar R, Azam S, Sullivan JM, Owen C, Cavener DR, Zhang
P, Ron D, Harding HP, Chen JJ, Han A, White BC, Krause GS, DeGracia
DJ.
Brain
ischemia and reperfusion activates the eukaryotic initiation factor
2a kinase,PERK. J. Neurochem.
2001;77:1418-1421.
- DeGracia DJ, Adamczyk S, Folbe AJ, Konkoly LL, Pittman JE, Neumar
RW, Sullivan JM, Scheuner DL, Kaufman RJ, White BC, Krause GS.
Eukaryotic
initiation factor 2a
(eIF2a) kinase and phosphatase activity during post-ischemic
brain reperfusion. Experimental
Neurology, 1999;155(2):221-227.
- DeGracia
DJ, Sullivan JM, Neumar RW, Alousi
SS, Hikade KR, Pittman JE, White BC, Rafols JA, Krause GS.
Effect of brain ischemia and reperfusion on the localization
of phosphorylated eukaryotic initiation factor 2a. J Cerebral Blood Flow and
Metabolism. 1997;17:1291-1302.
- DeGracia
DJ, Neumar RW, White, BC, Krause
GS. Global brain ischemia and reperfusion: Modifications
in eukaryotic initiation factors are associated with inhibition of
translation initiation. J Neurochem.
1996;67:2005-2012.
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