Kevin S. Lee

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  • Phone: 434-924-0262

Primary Appointment

Professor, Neuroscience

Education

  • BA, Psychology, University of Southern California
  • PhD, Psychobiology, University of California, Irvine

Research Disciplines

Biotechnology, Cancer Biology, Cardiovascular Biology, Experimental Pathology, Neuroimmunology, Neuroscience, Translational Science

Research Description

Our laboratory is interested in the cellular mechanisms of neuronal vulnerability associated with stroke. A multidisciplinary approach has been undertaken to elucidate how neurons are destabilized during ischemia and what mechanisms underlie the degenerative process. Knowledge from these basic investigations are then utilized to develop and test specific therapeutic strategies for rescuing damaged neurons. The specific mechanisms currently under investigation in the laboratory are listed below.
1. Post-ischemic hyperexcitability; the role of adenosine. Adenosine is a potent, endogenous anti-convulsant whose neuromodulatory actions are comprised following transient ischemia. The role of attenuated neuronal inhibition in the process neuronal death is being examined in selectively vulnerable hippocampal neurons.
2. The role of calpain in ischemic cell death. The elevation of intracellular calcium concentrations plays a critical role in cellular damage in a variety of disease states. These studies are examining the role of calcium-activated, intracellular proteases in the cell death process.
3. Effects of calpain inhibitors on focal cerebral ischemia. Activation of the protease, calpain has been implicated in the process of ischemic neuronal death. Newly-developed inhibitors of calpain are being tested for their potential neuroprotective influence in a model of reversible, focal ischemica.
4. Cerebrovascular effects of novel peptides in cerebral vasospasm. Protein kinase C and calponin are important regulators of vascular contractility and are preferred substrates for calcium-activated proteolysis are being studies in models of cerebral vasospasm to determine their influence on pathological vascular constriction.
5. Neurovascular communication in the CNS. The manner in which microvascular tone is couple to neuronal activity in the parenchyma of the CNS is under investigation. The roles of excitatory and inhibitory transmitters in signaling microvessels are being clarified.
6. Development of the mammalian neocortex. Neuocortical development is being investigated in a novel mutant rat which exhibits a double cortex. This type of neocortical malformation may underlie certain forms of epilepsy.
This research is funded by the National Institutes of Health, the National Science Foundation, the Upjohn Company, Cortex Pharmaceuticals, Chugai Pharmaceuticals, Ciba Geigy, and Elekta Instruments.

Personal Statement

Our laboratory is interested in the cellular mechanisms of neuronal vulnerability associated with stroke. A multidisciplinary approach has been undertaken to elucidate how neurons are destabilized during ischemia and what mechanisms underlie the degenerative process. Knowledge from these basic investigations are then utilized to develop and test specific therapeutic strategies for rescuing damaged neurons. The specific mechanisms currently under investigation in the laboratory are listed below.
1. Post-ischemic hyperexcitability; the role of adenosine. Adenosine is a potent, endogenous anti-convulsant whose neuromodulatory actions are comprised following transient ischemia. The role of attenuated neuronal inhibition in the process neuronal death is being examined in selectively vulnerable hippocampal neurons.
2. The role of calpain in ischemic cell death. The elevation of intracellular calcium concentrations plays a critical role in cellular damage in a variety of disease states. These studies are examining the role of calcium-activated, intracellular proteases in the cell death process.
3. Effects of calpain inhibitors on focal cerebral ischemia. Activation of the protease, calpain has been implicated in the process of ischemic neuronal death. Newly-developed inhibitors of calpain are being tested for their potential neuroprotective influence in a model of reversible, focal ischemica.
4. Cerebrovascular effects of novel peptides in cerebral vasospasm. Protein kinase C and calponin are important regulators of vascular contractility and are preferred substrates for calcium-activated proteolysis are being studies in models of cerebral vasospasm to determine their influence on pathological vascular constriction.
5. Neurovascular communication in the CNS. The manner in which microvascular tone is couple to neuronal activity in the parenchyma of the CNS is under investigation. The roles of excitatory and inhibitory transmitters in signaling microvessels are being clarified.
6. Development of the mammalian neocortex. Neuocortical development is being investigated in a novel mutant rat which exhibits a double cortex. This type of neocortical malformation may underlie certain forms of epilepsy.
This research is funded by the National Institutes of Health, the National Science Foundation, the Upjohn Company, Cortex Pharmaceuticals, Chugai Pharmaceuticals, Ciba Geigy, and Elekta Instruments.

Training

  • Predoctoral Training in Neuroscience

Selected Publications

2023

Zhang, Y., Keunen, O., Golebiewska, A., Gerosa, M., Wang, J., Ghobadi, S. N., . . . Wintermark, M. (2023). Immune cell identity behind the Ktrans mapping of mouse glioblastoma. MAGNETIC RESONANCE IMAGING, 103, 92-101. doi:10.1016/j.mri.2023.06.008

2022

Wang, Y., Machizawa, M. G., Lisle, T., Williams, C. L., Clarke, R., Anzivino, M., . . . Lee, K. S. (2022). Suppression of Neuroinflammation Attenuates Persistent Cognitive and Neurogenic Deficits in a Rat Model of Cardiopulmonary Bypass. FRONTIERS IN CELLULAR NEUROSCIENCE, 16. doi:10.3389/fncel.2022.780880

2021

Wang, Y., Anzivino, M. J., Zhang, Y., Bertram, E. H., Woznak, J., Klibanov, A. L., . . . Lee, K. S. (2021). Noninvasive disconnection of targeted neuronal circuitry sparing axons of passage and nonneuronal cells. JOURNAL OF NEUROSURGERY, 137(1), 296-306. doi:10.3171/2021.7.JNS21123

Zhang, Y., Buckmaster, P. S., Qiu, L., Wang, J., Keunen, O., Ghobadi, S. N., . . . Wintermark, M. (2021). Non-invasive, neurotoxic surgery reduces seizures in a rat model of temporal lobe epilepsy. EXPERIMENTAL NEUROLOGY, 343. doi:10.1016/j.expneurol.2021.113761

2020

Wang, W., Zhang, Y., Anzivino, M. J., Bertram, E. H., Woznak, J., Klibanov, A., . . . Lee, K. S. (2020). Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (163). doi:10.3791/61271

Grosenbaugh, D. K., Joshi, S., Fitzgerald, M. P., Lee, K. S., Wagley, P. K., Koeppel, A. F., . . . Goodkin, H. P. (2020). A deletion in Eml1 leads to bilateral subcortical heterotopia in the tish rat. NEUROBIOLOGY OF DISEASE, 140. doi:10.1016/j.nbd.2020.104836

Zhang, Y., Zhou, H., Qu, H., Liao, C., Jiang, H., Huang, S., . . . Wintermark, M. (2020). EFFECTS OF NON-INVASIVE, TARGETED, NEURONAL LESIONS ON SEIZURES IN A MOUSE MODEL OF TEMPORAL LOBE EPILEPSY. ULTRASOUND IN MEDICINE AND BIOLOGY, 46(5), 1224-1234. doi:10.1016/j.ultrasmedbio.2020.01.008

Wang, Y., Tache-Leon, C., Machizawa, M. G., Lisle, T., Williams, C., Clarke, R. H., . . . Lee, K. S. (2020). Persistent cognitive deficits and neuroinflammation in a rat model of cardiopulmonary bypass. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 160(4), E185-E188. doi:10.1016/j.jtcvs.2019.12.070

2016

Li, Y., Bor, Y. -C., Fitzgerald, M. P., Lee, K. S., Rekosh, D., & Hammarskjold, M. -L. (2016). An NXF1 mRNA with a retained intron is expressed in hippocampal and neocortical neurons and is translated into a protein that functions as an Nxf1 cofactor. MOLECULAR BIOLOGY OF THE CELL, 27(24), 3903-3912. doi:10.1091/mbc.E16-07-0515

Filiano, A. J., Xu, Y., Tustison, N. J., Marsh, R. L., Baker, W., Smirnov, I., . . . Kipnis, J. (2016). Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour. NATURE, 535(7612), 425-+. doi:10.1038/nature18626

Zhang, Y., Tan, H., Bertram, E. H., Aubry, J. -F., Lopes, M. -B., Roy, J., . . . Wintermark, M. (2016). NON-INVASIVE, FOCAL DISCONNECTION OF BRAIN CIRCUITRY USING MAGNETIC RESONANCE-GUIDED LOW-INTENSITY FOCUSED ULTRASOUND TO DELIVER A NEUROTOXIN. ULTRASOUND IN MEDICINE AND BIOLOGY, 42(9), 2261-2269. doi:10.1016/j.ultrasmedbio.2016.04.019

2015

Wang, Y., Schretter, C., Clarke, R., & Lee, K. S. (2015). Perihematomal Cellular Injury Is Reduced by Trans-sodium Crocetinate in a Model of Intracerebral Hemorrhage. MOLECULAR NEUROBIOLOGY, 52(2), 985-989. doi:10.1007/s12035-015-9245-8

Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., . . . Kipnis, J. (2015). Structural and functional features of central nervous system lymphatic vessels. NATURE, 523(7560), 337-+. doi:10.1038/nature14432

2014

Zhang, Y., Aubry, J. -F., Zhang, J., Wang, Y., Roy, J., Mata, J. F., . . . Wintermark, M. (2015). DEFINING THE OPTIMAL AGE FOR FOCAL LESIONING IN A RAT MODEL OF TRANSCRANIAL HIFU. ULTRASOUND IN MEDICINE AND BIOLOGY, 41(2), 449-455. doi:10.1016/j.ultrasmedbio.2014.09.029

Zhang, Y., Wang, Y., Zuo, Z., Wang, Z., Roy, J., Hou, Q., . . . Winterrnark, M. (2014). Effects of tissue plasminogen activator timing on blood-brain barrier permeability and hemorrhagic transformation in rats with transient ischemic stroke. JOURNAL OF THE NEUROLOGICAL SCIENCES, 347(1-2), 148-154. doi:10.1016/j.jns.2014.09.036

Wang, Y., Yoshimura, R., Manabe, H., Schretter, C., Clarke, R., Cai, Y., . . . Lee, K. S. (2014). Trans-sodium crocetinate improves outcomes in rodent models of occlusive and hemorrhagic stroke. BRAIN RESEARCH, 1583, 245-254. doi:10.1016/j.brainres.2014.08.013

Clarke, R. H., Moosa, S., Anzivino, M., Wang, Y., Floyd, D. H., Purow, B. W., & Lee, K. S. (2014). Sustained Radiosensitization of Hypoxic Glioma Cells after Oxygen Pretreatment in an Animal Model of Glioblastoma and In Vitro Models of Tumor Hypoxia. PLOS ONE, 9(10). doi:10.1371/journal.pone.0111199

2011

Manabe, H., Wang, Y., Yoshimura, R., Cai, Y., Fitzgerald, M., Clarke, R., & Lee, K. S. (2011). Metabolic Reflow as a Therapy for Ischemic Brain Injury. EARLY BRAIN INJURY OR CEREBRAL VASOSPASM, VOL 2: CLINICAL MANAGEMENT, 110, 87-91. doi:10.1007/978-3-7091-0356-2_16

2010

Fitzgerald, M. P., Covio, M., & Lee, K. S. (2011). DISTURBANCES IN THE POSITIONING, PROLIFERATION AND APOPTOSIS OF NEURAL PROGENITORS CONTRIBUTE TO SUBCORTICAL BAND HETEROTOPIA FORMATION. NEUROSCIENCE, 176, 455-471. doi:10.1016/j.neuroscience.2010.12.003

Manabe, H., Okonkwo, D. O., Gainer, J. L., Clarke, R. H., & Lee, K. S. (2010). Protection against focal ischemic injury to the brain by trans-sodium crocetinate. JOURNAL OF NEUROSURGERY, 113(4), 802-809. doi:10.3171/2009.10.JNS09562