Research Topics
Genomes and Genes | Rajiv R RatanSummaryAffiliation: Weill Medical College of Cornell University Country: USA Publications
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Publications
Small molecule activation of adaptive gene expression: tilorone or its analogs are novel potent activators of hypoxia inducible factor-1 that provide prophylaxis against stroke and spinal cord injuryRajiv R Ratan
Burke Cornell Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY 10605, USA
Ann N Y Acad Sci 1147:383-94. 2008..Altogether these findings identify tilorone as a novel and potent modulator of HIF-mediated gene expression in neurons with neuroprotective properties...- Novel multi-modal strategies to promote brain and spinal cord injury recoveryRajiv R Ratan
Winifred Masterson Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Stroke 40:S130-2. 2009..We conclude that combinations of interventions will be needed to surmount the multiple barriers to recovery in stroke and other types of brain and spinal cord injury recovery... - Harnessing hypoxic adaptation to prevent, treat, and repair strokeRajiv R Ratan
Winifred Masterson Burke Medical Research Institute, White Plains, NY 10605, USA
J Mol Med (Berl) 85:1331-8. 2007..The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics... - Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington diseaseStephen J McConoughey
Burke Medical Research Institute, White Plains, NY, USA
EMBO Mol Med 2:349-70. 2010..Altogether these findings demonstrate that selective TG inhibition broadly corrects transcriptional dysregulation in HD and defines a novel HDAC-independent epigenetic strategy for treating neurodegeneration... - Transglutaminase inhibition protects against oxidative stress-induced neuronal death downstream of pathological ERK activationManuela Basso
Winifred Masterson Burke Medical Research Institute, White Plains, NY 10605, USA
J Neurosci 32:6561-9. 2012.... - HDAC6 is a target for protection and regeneration following injury in the nervous systemMark A Rivieccio
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Proc Natl Acad Sci U S A 106:19599-604. 2009..Together, these findings define HDAC6 as a potential nontoxic therapeutic target for ameliorating CNS injury characterized by oxidative stress-induced neurodegeneration and insufficient axonal regeneration... - A large-scale chemical screen for regulators of the arginase 1 promoter identifies the soy isoflavone daidzeinas a clinically approved small molecule that can promote neuronal protection or regeneration via a cAMP-independent pathwayThong C Ma
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 30:739-48. 2010.... - HIF prolyl hydroxylase inhibitors prevent neuronal death induced by mitochondrial toxins: therapeutic implications for Huntington's disease and Alzheimer's diseaseZoya Niatsetskaya
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
Antioxid Redox Signal 12:435-43. 2010.... - Prolyl 4-hydroxylase activity-responsive transcription factors: from hydroxylation to gene expression and neuroprotectionAmbreena Siddiq
Burke Medical Research Institute, White Plains, New York 10605, USA
Front Biosci 13:2875-87. 2008.... 
Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegenerationSama F Sleiman
Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 31:6858-70. 2011..These results support a model in which cancer cell transformation shares key genetic components with neurodegeneration...- ATF4 is an oxidative stress-inducible, prodeath transcription factor in neurons in vitro and in vivoPhilipp S Lange
Burke Medical Research Institute, White Plains, NY 10605, USA
J Exp Med 205:1227-42. 2008..Collectively, these findings establish ATF4 as a redox-regulated, prodeath transcriptional activator in the nervous system that propagates death responses to oxidative stress in vitro and to stroke in vivo... - 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) protects neurons from oxidative death via an Nrf2 astrocyte-specific mechanism independent of PPARγRENEE E HASKEW-LAYTON
The Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, White Plains, NY 10605, USA
J Neurochem 124:536-47. 2013.... - Development of Neh2-luciferase reporter and its application for high throughput screening and real-time monitoring of Nrf2 activatorsNatalya A Smirnova
Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, White Plains, NY 10605, USA
Chem Biol 18:752-65. 2011..The most robust and yet nontoxic Nrf2 activators found--nordihydroguaiaretic acid, fisetin, and gedunin--induced astrocyte-dependent neuroprotection from oxidative stress via an Nrf2-dependent mechanism... - Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathwaysAmbreena Siddiq
Department of Neurosciences, Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 29:8828-38. 2009.... - Histone deacetylase inhibitors de-repress tyrosine hydroxylase expression in the olfactory bulb and rostral migratory streamYosuke Akiba
Burke Medical Research Institute, 785 Mamaroneck Ave, White Plains, NY 10605, USA
Biochem Biophys Res Commun 393:673-7. 2010.... - Utilization of an in vivo reporter for high throughput identification of branched small molecule regulators of hypoxic adaptationNatalya A Smirnova
Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 785 Mamaroneck Ave, White Plains, NY 10605, USA
Chem Biol 17:380-91. 2010.... - Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotectionBrett Langley
Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 28:163-76. 2008.... - Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathwayRENEE E HASKEW-LAYTON
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, The Burke Medical Research Institute, White Plains, NY 10605, USA
Proc Natl Acad Sci U S A 107:17385-90. 2010..These findings demonstrate the utility of rgDAAO for spatially and temporally controlling intracellular H(2)O(2) concentrations to uncover unique astrocyte-dependent neuroprotective mechanisms... - Arginase 1 regulation of nitric oxide production is key to survival of trophic factor-deprived motor neuronsALVARO G ESTEVEZ
Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 26:8512-6. 2006..They also suggest that the resistance of motor neuron subpopulations to trophic factor deprivation may result from increased arginase activity... - Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stressAmbreena Siddiq
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Neurochem Res 32:931-46. 2007.... 
Translation of ischemic preconditioning to the patient: prolyl hydroxylase inhibition and hypoxia inducible factor-1 as novel targets for stroke therapyRajiv R Ratan
Department of Neurology and Neuroscience, Burke Cornell Medical Research Institute, Weill Medical College of Cornell, White Plains, NY 10605, USA
Stroke 35:2687-9. 2004..Here, we review evidence suggesting that the HIF-1 prolyl hyroxylases are inhibited during ischemic preconditioning and that pharmacological inhibitors of these enzymes are viable targets for stroke therapy...- Remodeling chromatin and stress resistance in the central nervous system: histone deacetylase inhibitors as novel and broadly effective neuroprotective agentsBrett Langley
Burke Medical Research Institute, White Plains, NY 10605, USA
Curr Drug Targets CNS Neurol Disord 4:41-50. 2005..These studies demonstrate that pharmacological HDAC inhibition is a promising therapeutic approach for the treatment of a range of central nervous system disorders... - Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseasesGary E Gibson
Department of Neurology and Neuroscience, Weill Cornell Medical College of Cornell University at Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Biochim Biophys Acta 1802:122-34. 2010..Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic approaches in age-associated neurodegenerative diseases... - Histone Deacetylase Inhibitors and Mithramycin A Impact a Similar Neuroprotective Pathway at a Crossroad between Cancer and NeurodegenerationSama F Sleiman
Burke Cornell Medical Research Institute, 785 Mamaroneck Ave, White Plains, New York, NY 10605, USA
Pharmaceuticals (Basel) 4:1183-1195. 2011..These findings support the conclusion that an imbalance in histone acetylase and HDAC activity in favor of HDACs is key not only for oncogenic transformation, but also neurodegeneration... - CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cellsJoann M Gensert
The Winifred Masterson Burke Cornell Medical Research Institute, 785 Mamaroneck Ave, White Plains, NY 10605, USA
Neurobiol Dis 26:671-80. 2007..Induction of CD81 expression through HDAC inhibition is a novel strategy to promote growth arrest in glioma cells... - Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's diseaseGabriella Gardian
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA
J Biol Chem 280:556-63. 2005.... - A nonradioactive dot blot assay for transglutaminase activityStephen J McConoughey
Burke Medical Research Institute, White Plains, NY 10605, USA
Anal Biochem 390:91-3. 2009.... - Hypoxia-inducible factor prolyl hydroxylase inhibition: robust new target or another big bust for stroke therapeutics?Saravanan S Karuppagounder
Center for Stroke Recovery, Burke Medical Research Institute, White Plains, NY, USA
J Cereb Blood Flow Metab 32:1347-61. 2012..In this review, we discuss this evidence and highlight important gaps in our understanding that render HIF PHD inhibition a promising but not yet preclinically validated target for protection and repair after stroke... - Putting the 'HAT' back on survival signalling: the promises and challenges of HDAC inhibition in the treatment of neurological conditionsSama F Sleiman
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, 10605 NY, USA
Expert Opin Investig Drugs 18:573-84. 2009..Despite the fact that HDAC inhibitors are in an advanced stage of development, we suggest other approaches to modulating HDAC function that may be less toxic and more efficacious than the canonical agents developed so far... - miR-886-3p levels are elevated in Friedreich ataxiaLata H Mahishi
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10065, USA
J Neurosci 32:9369-73. 2012..These results outline involvement of a small RNA, miR-886-3p in FRDA and a novel therapeutic approach to this disease using an anti-miR-886-3p... - Transglutaminase activity is present in highly purified nonsynaptosomal mouse brain and liver mitochondriaBoris F Krasnikov
Department of Neurology and Neurosciences, and Medicine, Weill Medical College of Cornell University, New York City, New York 10021, USA
Biochemistry 44:7830-43. 2005..This activity may play a role in regulation of mitochondrial function both in normal physiology and in disease. Its nature and regulation deserve further study... - The metabolic coupling of arginine metabolism to nitric oxide generation by astrocytesJoann M Gensert
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
Antioxid Redox Signal 8:919-28. 2006..Thus, neural and nonneural cells act in concert to affect neuron physiology in an elegantly integrated system. This review focuses on the components of the interaction between astrocytes and neurons in nitric oxide biology... - In vitro model of oxidative stress in cortical neuronsRajiv R Ratan
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
Methods Enzymol 352:183-90. 2002 - The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanismPaul C Chin
Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083, USA
J Neurochem 90:595-608. 2004.... - Oxidative stress-induced death in the nervous system: cell cycle dependent or independent?Brett Langley
Department of Neurology, Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Neurosci Res 77:621-9. 2004..The determining factor for which or how many pathways are induced appears to be context dependent and determined by the level and duration of oxidative stress... - Prosurvival and prodeath effects of hypoxia-inducible factor-1alpha stabilization in a murine hippocampal cell lineLeila R Aminova
Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:3996-4003. 2005..Together, these data demonstrate that HIF-1 can mediate prodeath or prosurvival responses in the same cell type depending on the injury stimulus... - Proteasome inhibition protects HT22 neuronal cells from oxidative glutamate toxicityKlaus van Leyen
Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
J Neurochem 92:824-30. 2005..These findings suggest that caspases can be decoupled from oxidative stress under some conditions, and implicate the ubiquitin/proteasome pathway in neuronal cell death caused by oxidative glutamate toxicity... - Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradoxJunghee Lee
Deparment of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4843-8. 2003..These results provide an explanation for the arginine paradox for iNOS and define a distinct mechanism by which a substrate can regulate the activity of its associated enzyme... - Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous systemAmbreena Siddiq
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:41732-43. 2005..Taken together these findings identified low molecular weight and peptide HIF prolyl 4-hydroxylase inhibitors as novel neurological therapeutics for stroke as well as other diseases associated with oxidative stress... - Oxygen-sensitive reset of hypoxia-inducible factor transactivation response: prolyl hydroxylases tune the biological normoxic set pointSavita Khanna
Laboratory of Molecular Medicine, Davis Heart and Lung Research Institute, Department of Surgery, The Ohio State University Medical Center, Columbus, 43210, USA
Free Radic Biol Med 40:2147-54. 2006..siRNA dependent knockdown of PHD expression revealed that O(2)-sensitive regulation of PHD may contribute to tuning the normoxic set point in biological cells... - Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathwayHoon Ryu
Department of Neurology and Program in Neuroscience, Harvard Medical School and Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4281-6. 2003..Together, these results demonstrate that HDAC inhibitors inhibit oxidative death independent of polyglutamine expansions by activating an Sp1-dependent adaptive response... - The role of iron neurotoxicity in ischemic strokeMagdy H Selim
Department of Neurology, Division of Cerebrovascular Diseases, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Palmer 127, Boston, MA 02215, USA
Ageing Res Rev 3:345-53. 2004..Understanding the changes in brain iron metabolism and its relationship to neuronal injury in ischemic stroke could provide new therapeutic targets to improve the outcome of stroke patients... - Novel changes in gene expression following axotomy of a sympathetic ganglion: a microarray analysisKristen L Boeshore
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
J Neurobiol 59:216-35. 2004..In addition, the data suggest a potential role for putrescine and spermidine, acting downstream of arg I, in the regenerative process... - Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease miceRobert J Ferrante
Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, USA
J Neurosci 23:9418-27. 2003.... - Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegenerationSavita Khanna
Laboratory of Molecular Medicine, Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio 43210, USA
J Biol Chem 278:43508-15. 2003..These findings lend further support to alpha-tocotrienol as a potent neuroprotective form of vitamin E... - Therapeutic effects of cystamine in a murine model of Huntington's diseaseAlpaslan Dedeoglu
Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, USA
J Neurosci 22:8942-50. 2002..These findings are consistent with the hypothesis that transglutaminase activity may play a role in the pathogenesis of HD, and they identify cystamine as a potential therapeutic strategy for treating HD patients... - Sp1 and Sp3 are oxidative stress-inducible, antideath transcription factors in cortical neuronsHoon Ryu
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurosci 23:3597-606. 2003..Taken together, these results establish Sp1 and Sp3 as oxidative stress-induced transcription factors in cortical neurons that positively regulate neuronal survival... - Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage responseJunghee Lee
Geriatric Research Education and Clinical Center, Bedford Veteran s Affairs Medical Center, 200 Springs Rd, Bedford, MA 01730, USA
FASEB J 20:2375-7. 2006..These results indicate that in primary neurons Sp1 and Sp3 play an essential role in the modulation of COX-2 transcription, which mediates neuronal homeostasis and survival by preventing DNA damage in response to neuronal stress... - Novel roles for arginase in cell survival, regeneration, and translation in the central nervous systemPhilipp S Lange
Department of Neurology, Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston MA 02115, USA
J Nutr 134:2812S-2817S; discussion 2818S-2819S. 2004..Beyond molecular mechanisms, this review will also include relevant clinical findings in patients with neurodegenerative diseases... - Mining genome databases for therapeutic gold: SIM2 is a novel target for treatment of solid tumorsRajiv R Ratan
Department of Neurology, Program in Neuroscience, and Center for Neurodegeneration and Repair, Harvard Medical School and Burke/Cornell Medical Research Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Trends Pharmacol Sci 24:508-10. 2003 - cAMP response element binding protein family transcription factors: the Holy Grail of neurological therapeutics?Rajiv R Ratan
Ann Neurol 56:607-8. 2004 - Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's diseaseRobert J Ferrante
Geriatric Research and Education and Clinical Center, Veterans Administration Medical Center, Bedford, MA, USA
J Neurosci 24:10335-42. 2004..Because it is Food and Drug Administration-approved, mithramycin is a promising drug for the treatment of HD... - Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neuronsHoon Ryu
Geriatric Research Education and Clinical Center, Veteran s Affairs Medical Center, Bedford, MA 01730, USA
Proc Natl Acad Sci U S A 102:13915-20. 2005..These results suggest that the regulation of mitochondrial function via the mitochondrial PKA and CREB pathways may underlie some of the salutary effects of DFO in neurons... - Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survivalJunghee Lee
Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 280:40398-401. 2005.... - The histone deacetylase inhibitor sodium butyrate protects against cisplatin-induced hearing loss in guinea pigsMarie Drottar
Department of Otolaryngology, Children's Hospital, and the Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA
Laryngoscope 116:292-6. 2006..Because histone deacetylase inhibitors are anticancer agents with very few side effects, they may be candidates for clinical use during cisplatin chemotherapy... - Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitisSandra Camelo
Laboratory of Transcriptional and Immune Regulation, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02139, USA
J Neuroimmunol 164:10-21. 2005..A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance... - Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitroDongming Cai
Biology Department, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10024, USA
Neuron 35:711-9. 2002..Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury...