John M. Hallenbeck, M.D.
Clinical Investigations Section
Building 10, Room 5B02
10 Center Drive
Bethesda, MD 20892-1401
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.
Bernstock JD, Peruzzotti-Jametti L, Ye D, Gessler FA, Maric D, Vicario N, Lee YJ, Pluchino S, Hallenbeck JM. Neural stem cell transplantation in ischemic stroke: A role for preconditioning and cellular engineering. J Cereb Blood Flow Metab. 2017;37(7):2314-2319.
Lee YJ, Mou Y, Klimanis D, Bernstock JD, Hallenbeck JM. Global SUMOylation is a molecular mechanism underlying hypothermia-induced ischemic tolerance. Front Cell Neurosci. 2014;8:416.
Wakita H, Ruetzler C, Illoh KO, Chen Y, Takanohashi A, Spatz M, Hallenbeck JM. Mucosal tolerization to E-selectin protects against memory dysfunction and white matter damage in a vascular cognitive impairment model. J Cereb Blood Flow Metab. 2008;28(2):341-53.
Lee YJ, Miyake S, Wakita H, McMullen DC, Azuma Y, Auh S, Hallenbeck JM. Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells. J Cereb Blood Flow Metab. 2007;27(5):950-62.
Bernstock JD, Lee YJ, Peruzzotti-Jametti L, Southall N, Johnson KR, Maric D, Volpe G, Kouznetsova J, Zheng W, Pluchino S, Hallenbeck JM. A novel quantitative high-throughput screen identifies drugs that both activate SUMO conjugation via the inhibition of microRNAs 182 and 183 and facilitate neuroprotection in a model of oxygen and glucose deprivation. J Cereb Blood Flow Metab. 2016;36(2):426-41.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on May 22nd, 2017