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Scientist Emeritus

John M. Hallenbeck, M.D.

Clinical Investigations Section

Stroke Branch, NINDS
Building 10 Room 5B02
10 Center Drive MSC 1401
Bethesda MD 20892-1401
Office: (301) 496-6231
Lab: (301) 496-6231
Fax: (301) 402-2769
HallenbJ@ninds.nih.gov

Dr. Hallenbeck received his M.D. degree from the University of Pennsylvania. After a medical internship and neurology residency at the University of Michigan, he entered the United States Navy. At the Naval Medical Research Institute his research focused on CNS decompression sickness and air embolism and later the study of inflammatory and immune mechanisms in acute brain ischemia. In 1983, he was appointed Chief of the Navy's neurology training program at the National Naval Medical Center and Professor, Vice-Chairman and Chairman for Research in the Department of Neurology, Uniformed Services University of the Health Sciences. In 1991 he came to the NINDS as Chief of the newly created Stroke Branch. He received the Mihara Cerebrovascular Disorder Research Prize. Dr. Hallenbeck's laboratory is studying the cellular regulation of ischemic tolerance and inflammatory and immune mechanisms in the initiation and progression of stroke.



The Clinical Investigations Section of the Stroke Branch conducts translational research on stroke prevention and stroke treatment. In spontaneously hypertensive, stroke-prone rats, we are studying ways of preventing development of spontaneous brain infarcts. This work is focused on immunologic approaches that suppress the endothelial activation produced by inflammatory cytokines such as TNF and IL-1. Mucosal tolerization to E-selectin targets immunomodulation to vascular segments that are becoming activated and suppresses spontaneous strokes and hemorrhages. This work is being translated into clinical trials.

We also study endogenous neuroprotective mechanisms that induce tolerance to hypoxia and ischemia in brain cells. This work is focused on the intracellular signaling pathways and expressed genes that regulate tolerance to hypoxia and ischemia in hibernating animals (a model of natural tolerance), and in preclinical stroke models and primary cultures of brain microvessel endothelial cells, astrocytes, microglia, cortical neurons and transformed cell lines that have been preconditioned to induce tolerance (models of induced tolerance). Multifunctional regulatory mechanisms that are conserved in the several tolerance models are of particular interest. Findings in preclinical models that have robust potential to treat stroke are candidates for translation into proof of concept clinical trials.

Staff Image
  • Joshua D. Bernstock, MSc, MPH, MD/PhD Candidate
    NIH-OxCam Predoctoral Fellow
    (301) 594 2548

  • Dace Klimanis, M.Sc
    Research Assistant
    (301) 402-2338

  • Yang-Ja Lee-Wickner, Ph.D.
    Staff Scientist
    (301) 402-6939

  • Yongshan Mou, M.D.
    Senior Research Fellow
    (301) 594-2597

  • Maria Spatz, M.D.
    Special Volunteer
    (301) 496-8111

  • Daniel Ye, B.Sc.
    Post baccalaureate IRTA Fellow

  • 1) Choi SH, Arai AL, Mou Y, Kang B, Yen CC, Hallenbeck J, Silva AC (2018)
  • Neuroprotective Effects of MAGL (Monoacylglycerol Lipase) Inhibitors in Experimental Ischemic Stroke
  • Stroke, 49(3), 718-726
  • 2) Ishibashi S, Maric D, Mou Y, Ohtani R, Ruetzler C, Hallenbeck JM (2009)
  • Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats
  • J Cereb Blood Flow Metab, 29, 606-20
  • 3) Lee YJ, Castri P, Bembry J, Maric D, Auh S, Hallenbeck JM (2009)
  • SUMOylation participates in induction of ischemic tolerance
  • J Neurochem, 109, 257-67
  • 4) Wakita H, Ruetzler C, Illoh KO, Chen Y, Takanohashi A, Spatz M, Hallenbeck JM (2008)
  • Mucosal tolerization to E-selectin protects against memory dysfunction and white matter damage in a vascular cognitive impairment model
  • J Cereb Blood Flow Metab. , 28, 341-53
  • 5) Lee Y, Miyake S, Wakita H, McMullen DC, Azuma Y, Auh S, Hallenbeck JM (2007)
  • Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SH SY 5Y cells
  • J Cereb Blood Flow Metab , 27, 950-62
  • 6) Bratincsák A, McMullen D, Miyake S, Tóth ZE, Hallenbeck JM, Palkovitz M (2007)
  • Spatial and temporal activation of brain regions in hibernation: c-fos expression during the hibernation bout in thirteen-lined ground squirrel
  • J. Comp. Neurol, 505, 443-458
  • 7) Hallenbeck J, del Zoppo G, Jacobs T, Hakim A, Goldman S, Utz U, Hasan A (2006)
  • Immunomodulation strategies for preventing vascular disease of the brain and heart
  • STROKE, 37, 3035-3042
  • 8) Chamorro A, Hallenbeck J (2006)
  • The harms and benefits of inflammatory and immune responses in vascular disease
  • Stroke, 37, 291-293
  • 9) Hallenbeck JM, Hansson GK, Becker KJ. (2005)
  • Immunology of vascular disease: plaque to attack
  • TRENDS in Immunology , 26, 550-56
  • 10) Becker KJ, Hindrick D, Kim Y, McCarron RM, Hallenbeck JM (2003)
  • Adoptive transfer of MBP-tolerized splenocytes to naïve animals reduces infarct size: a role for lymphocytes in ischemic injury?
  • Stroke, 34, 1809-1815
  • 11) Dirnagl U,Simon RP,Hallenbeck JM (2003)
  • Ischemic tolerance and endogenous neuroprotection.
  • Trends Neurosci , 26 , 248-54
  • 12) Chen Y,Hallenbeck JM,Ruetzler C,Bol D,Thomas K,Berman NE,Vogel SN (2003)
  • Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells.
  • J Cereb Blood Flow Metab , 23 , 748-55
  • 13) Chen Y,Ruetzler C,Pandipati S,Spatz M,McCarron RM,Becker K,Hallenbeck JM (2003)
  • Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury.
  • Proc Natl Acad Sci U S A , 100 , 15107-12
  • 14) Ginis I, Jaiswal R, Klimanis D, Liu J, Greenspon J, Hallenbeck JM (2002)
  • TNF-alpha-induced tolerance to ischemic injury involves differential control of NFkappaB transactivation: the role of NFkappaB association with p300 adaptor
  • J Cereb Blood Flow Metab, 22, 142-152
  • 15) Hallenbeck JM (2002)
  • The many faces of tumor necrosis factor in stroke
  • Nature Medicine, 8, 1363-1368
  • 16) Takeda H, Spatz M, Ruetzler C, McCarron R, Becker K, Hallenbeck J (2002)
  • Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke-prone rats
  • Stroke, 33, 2156-63
  • 17) Takeda H, Spatz M, Ruetzler C, McCarron R, Becker K, Hallenbeck JM (2002)
  • Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke-prone rats
  • Stroke, 33, 2156-2164
  • 18) Chen Y, Matsushita M, Nairn AC, Damuni Z, Cai D, Frerichs KU, Hallenbeck JM (2001)
  • Mechanisms for increased phosphorylation of elongation factor-2 during hibernation in ground squirrels
  • Biochemistry, 40, 11565-11570
  • 19) Chen Y, Ginis I, Hallenbeck JM (2001)
  • The protective effect of ceramide in immature rat brain hypoxia-ischemia involves upregulation of Bcl-2 and reduction of TUNEL-positive cells
  • J Cereb Blood Flow Metab, 21, 34-40
  • 20) Ruetzler CA, Furuya K, Takeda H, Hallenbeck JM (2001)
  • Immunohistochemical analyses of rat brain sections suggest that vessel segments normally undergo cyclic, unsynchronized activation and inactivation
  • J Cereb Blood Flow Metab, 21, 244-252
  • 21) Furuya K, Ginis I, Takeda H, Hallenbeck JM (2001)
  • Cell permeable exogenous ceramide reduces infarct size in spontaneously hypertensive rats supporting in vitro studies that have implicated ceramide in induction of tolerance to ischemia.
  • J Cereb Blood Flow Metab, 21, 226-232
  • 22) Azzam NA, Hallenbeck JM, Kachar B (2000)
  • Phase separation of membrane lipids in the CNS during hibernation-induced hypothermia
  • Nature, 407, 317-318
  • 23) Liu J, Ginis I, Spatz M, Hallenbeck JM (2000)
  • Hypoxic preconditioning protects cultured neurons against hypoxic stress via TNF-alpha and ceramide
  • Am J Physiol (Cell Physiol), 278, C144-C153
  • 24) Dawson DA, Furuya K, Gotoh J, Yasuaki N, Hallenbeck JM (1999)
  • Cerebral hemodynamics and ischemic tolerance: Lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to changes in severity of the initial ischemic insult, but is associated with preservation of microvascular perfusion
  • J Cereb Blood Flow Metab, 19, 616-623
  • 25) Ginis I, Schweizer U, Brenner M, Liu J, Azzam N, Spatz M, Hallenbeck JM (1999)
  • Ceramide is a messenger for tolerance: TNF-alpha preconditioning attenuates response of cultured brain cells to TNF-alpha and hypoxia via a ceramide-dependent mechanism
  • Am J Physiol (Cell Physiol), 276, C1171-C1183
  • 26) Frerichs KU, Smith CB, Brenner M, DeGracia DJ, Krause GS, Marrone L, Dever TE, Hallenbeck JM (1998)
  • Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation
  • Proc Natl Acad Sci USA, 95, 14511-14516
  • 27) Becker KJ, McCarron RM, Ruetzler C, Laban O, Sternberg E, Flanders KC, Hallenbeck JM (1997)
  • Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia
  • Proc Natl Acad Sci USA, 94, 10873-10878
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